DB00006 Bivalirudin small molecule approved 128270-60-0 2180.2853 C98H138N24O33 P00734#Prothrombin Bivalirudin mediates an inhibitory action on thrombin by directly and specifically binding to both the catalytic site and anion-binding exosite of circulating and clot-bound thrombin. The action of bivalirudin is reversible because thrombin will slowly cleave the thrombin-bivalirudin bond which recovers the active site of thrombin. D09HVL DB00007 Leuprolide small molecule approved 53714-56-0 1209.3983 C59H84N16O12 D0U5FF DB00014 Goserelin small molecule approved 65807-02-5 1269.4105 C59H84N18O14 P22888#Lutropin-choriogonadotropic hormone receptor D00BCG DB00027 Gramicidin D small molecule approved 1405-97-6 1811.253 C96H135N19O16 Gramicidin is particularly effective against gram-positive bacteria. Because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution. D0J7XL DB00035 Desmopressin small molecule approved 16679-58-6 1069.22 C46H64N14O12S2 P30518#Vasopressin V2 receptor@P37288#Vasopressin V1a receptor@P47901#Vasopressin V1b receptor By mimicking the actions of endogenous ADH, desmopressin acts as a selective agonist of V2 receptors expressed in the renal collecting duct (CD) to increase water re-absorption and reduce urine production. Desmopressin has been shown to be more potent than ADH in increasing plasma levels of factor VIII activity in patients with hemophilia and von Willebrand's disease Type I 8. Desmopressin demonstrates markedly diminished pressor activity. Desmopressin administered intranasally has an antidiuretic effect about one-tenth that of an equivalent dose administered by injection 7. D0U7SH DB00050 Cetrorelix small molecule approved 120287-85-6 1431.038 C70H92ClN17O14 P30968#Gonadotropin-releasing hormone receptor@P22888#Lutropin-choriogonadotropic hormone receptor Cetrorelix is a synthetic decapeptide with gonadotropin-releasing hormone (GnRH) antagonistic activity. GnRH induces the production and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the gonadotrophic cells of the anterior pituitary. Due to a positive estradiol (E2) feedback at midcycle, GnRH liberation is enhanced resulting in an LH-surge. This LH-surge induces the ovulation of the dominant follicle, resumption of oocyte meiosis and subsequently luteinization as indicated by rising progesterone levels. Cetrorelix competes with natural GnRH for binding to membrane receptors on pituitary cells and thus controls the release of LH and FSH in a dose-dependent manner. D09OLZ DB00067 Vasopressin small molecule approved 11000-17-2 2140.46 C92H130N28O24S4 P37288#Vasopressin V1a receptor@P30518#Vasopressin V2 receptor D0N4OW DB00080 Daptomycin small molecule approved 103060-53-3 1620.693 C72H101N17O26 D05HPI DB00091 Cyclosporine small molecule approved 59865-13-3 1202.635 C62H111N11O12 P49069#Calcium signal-modulating cyclophilin ligand@Q96LZ3#Calcineurin subunit B type 2@P62937#Peptidyl-prolyl cis-trans isomerase A@P30405#Peptidyl-prolyl cis-trans isomerase F, mitochondrial Cyclosporine exerts potent immunosuppressive actions on T cells, thereby prolonging survival following organ and bone marrow transplants.24 This drug prevents and controls serious immune-mediated reactions including allograft rejection, graft versus host disease, and inflammatory autoimmune disease.24 DB00104 Octreotide small molecule approved 83150-76-9 1019.25 C49H66N10O10S2 Octreotide mimics the naturally occurring hormone known as somatostatin. Like somatostatin, it demonstrates activity against growth hormone and glucagon, treating the disordered tissue growth and insulin regulation in patients with acromegaly.6,8 In addition, octreotide relieves the flushing and diarrhea associated with gastrointestinal tumors by reducing splanchnic blood flow4 and various gastrointestinal hormones associated with diarrhea.2 D02XIY DB00106 Abarelix small molecule approved 183552-38-7 1416.09 C72H95ClN14O14 P30968#Gonadotropin-releasing hormone receptor Used in the palliative treatment of advanced prostate cancer. Abarelix is a luteinizing hormone agonist that results in suppression of testicular or follicular steroidogenesis. D01AHO DB12001 Abemaciclib small molecule approved 1231929-97-7 506.606 C27H32F2N8 P11802#Cyclin-dependent kinase 4@Q00534#Cyclin-dependent kinase 6 In combination with fulvestrant, the progression-free survival for patients with HR-positive, HER2-negative breast cancer was 16.4 months compared to 9.3 months for patients taking a placebo with fulvestrant. As a monotherapy, 19.7% of patients taking abemaciclib achieved complete or partial shrinkage of their tumors for a median 8.6 months after treatment 5. Abemaciclib induces cell cycle arrest and exerts an antitumor activity in human tumor xenograft models 1. DB12010 Fostamatinib small molecule approved 901119-35-5 580.4595 C23H26FN6O9P P43405#Tyrosine-protein kinase SYK The active metabolite of fostamatinib, R406, inhibits signal transduction by Fcγ receptors involved in the antibody-mediated destruction of platelets by immune cells in chronic ITP 1,2,Label. This results in increased platelet counts in this population. D0V8HJ DB12015 Alpelisib small molecule approved 1217486-61-7 441.47 C19H22F3N5O2S P42336#Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Alpelisib does not prolong the QTcF interval.7 Patients taking alpelisib experience a dose dependent benefit from treatment with a 51% advantage of a 200mg daily dose over a 100mg dose and a 22% advantage of 300mg once daily over 150mg twice daily.6 This suggests patients requiring a lower dose may benefit from twice daily dosing.6 D0W7HE DB12020 Tecovirimat small molecule approved 869572-92-9 376.335 C19H15F3N2O3 Tecovirimat is an antiviral drug that helps to prevent the spread of virus 10 and reduce viremia.2 It is effective against all orthopoxviruses tested in vitro, including variola or smallpox virus.1 D0MD8D DB12026 Voxilaprevir small molecule approved 1535212-07-7 868.94 C40H52F4N6O9S Voxilaprevir is a direct-acting antiviral agent that targets viral NS3/4A protein and causes a decrease in serum HCV RNA levels. It disrupts HCV replication by specifically inhibiting the critical functions of NS3/4A protein in the replication complex. It does not appear to prolong the QT interval even when given at 9 times the maximum recommended dose Label. DB12035 Sarecycline small molecule approved 1035654-66-0 487.509 C24H29N3O8 Compared to various examples of first-line tetracycline therapies for moderate to severe acne like doxycycline and minocycline, studies have shown that sarecycline can be sixteen to thirty-two fold less active against aerobic Gram-negative bacilli present within the normal human intestinal microbiome 1. Furthermore, it has also been demonstrated that sarecycline may be four to eight fold less active against various anaerobic bacteria that also comprise the normal human intestinal microbiome 1. Subsequently, while doxycycline and minocycline typically elicit broad-spectrum antimicrobial activity that can often cause adverse effects like diarrhea, fungal overgrowth, vaginal candidiasis, etc. due to undesirable off-target antibacterial effects on endogenous intestinal flora, sarecycline demonstrates a noticeably more target specific narrow spectrum activity with lower incidence of such side effects 1,2,3,Label. D0T6EI DB12070 Letermovir small molecule approved 917389-32-3 572.561 C29H28F4N4O4 F5HC79#Tripartite terminase subunit 1@F5HGI9#Tripartite terminase subunit 2@F5HCU8#Tripartite terminase subunit 3 Letermovir inhibits the activity of the DNA terminase complex of CMV thereby preventing the cutting of viral DNA into mature length genomes for packaging into viral particles Label. Letemovir inhibits the DNA terminase complex with an EC50 of 2.1nM. DB12091 Gadolinium small molecule approved 7440-54-2 157.25 Gd Not Available DB12095 Telotristat ethyl small molecule approved 1033805-22-9 574.99 C27H26ClF3N6O3 Q8IWU9#Tryptophan 5-hydroxylase 2@P17752#Tryptophan 5-hydroxylase 1 Activity is mainly in the gastrointestinal tract, with minimal effects reported on the brain and cardiovascular system, accompanied by an excellent safety profile. D0RE6T DB12097 Mannitol busulfan small molecule approved 1187-00-4 338.34 C8H18O10S2 Not Available DB01018 Guanfacine small molecule approved 29110-47-2 246.093 C9H9Cl2N3O P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Guanfacine is a selective alpha-2A adrenergic receptor agonist but it is unclear how this translates to the treatment of ADHD.11 It has a long duration of action as it is given once daily and a wide therapeutic window as fatal overdoses have not been described in literature.11 Patients should be counselled regarding the risk of hypotension, bradycardia, and syncope.11 DB01019 Bethanechol small molecule approved 674-38-4 161.2221 C7H17N2O2 P20309#Muscarinic acetylcholine receptor M3@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5 Bethanechol is selective for muscarinic receptors and has little to no impact on nicotinic receptors.1 The charged quaternary amine in the structure of bethanechol prevents it from crossing the blood-brain barrier which minimizes central nervous system related adverse effects.1 D07ZTO DB01020 Isosorbide mononitrate small molecule approved 16051-77-7 191.1388 C6H9NO6 P33402#Guanylate cyclase soluble subunit alpha-2 Isosorbide mononitrate is an anti-anginal agent and vasodilator that relaxes vascular smooth muscle to prevent and manage angina pectoris. The pharmacological action is mediated by the active metabolite, nitric oxide, which is released when isosorbide mononitrate is metabolized.3 Nitric oxide works on both arteries and veins, but predominantly veins: by relaxing veins and reducing the central venous pressure, nitric oxide causes venous pooling and a decrease in the venous return to the heart, thus decreasing cardiac preload.7 In healthy subjects, the stroke volume is decreased and venous pooling can occur in the standing posture, leading to postural hypotension and dizziness.3 DB01021 Trichlormethiazide small molecule approved 133-67-5 380.656 C8H8Cl3N3O4S2 P55017#Solute carrier family 12 member 3@P05023#Sodium/potassium-transporting ATPase subunit alpha-1@P00915#Carbonic anhydrase 1@P00918#Carbonic anhydrase 2@P22748#Carbonic anhydrase 4 Trichloromethiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Trichloromethiazide has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomer-ulonephritis, and chronic renal failure. Trichloromethiazide is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. Like other thiazides, Trichloromethiazide promotes water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. D0Y2IZ DB01022 Phylloquinone small molecule approved 84-80-0 450.6957 C31H46O2 P38435#Vitamin K-dependent gamma-carboxylase@P02818#Osteocalcin Phylloquinone is a vitamin K indicated in the treatment of coagulation disorders due to faulty formation of coagulation factors II, VII, IX, and X caused by deficiency or interference in the activity of vitamin K.17 It has a long duration of action as vitamin K is cycled in the body,6 and a wide therapeutic index as large doses can be tolerated.9,18 Patients should have their prothrombin time monitored during therapy and healthcare professionals should be aware of the increased risk of hypersensitivity reactions with parenteral administration.18 DB01023 Felodipine small molecule approved 72509-76-3 384.254 C18H19Cl2NO4 P0DP23#Calmodulin@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@P08235#Mineralocorticoid receptor@P63316#Troponin C, slow skeletal and cardiac muscles@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q01064#Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B@P54750#Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Felodipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Felodipine also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor. Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Felodipine also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Felodipine is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells. D0WN0U DB01024 Mycophenolic acid small molecule approved 24280-93-1 320.3371 C17H20O6 P12268#Inosine-5'-monophosphate dehydrogenase 2@P20839#Inosine-5'-monophosphate dehydrogenase 1 Mycophenolic acid is a potent inhibitor of inosine monophosphate dehydrogenase (IMPDH) that blocks de novo biosynthesis of purine nucleotides. This affects lymphocytes primarily and leads to the suppression of DNA synthesis in T- and B-cells.3,8 Mycophenolic acid arrests the T-lymphocyte cell cycle at the G1/S interface and inhibits the proliferation of lymphocytes.3 Also, it has been suggested that mycophenolic acid suppresses cytokine production by limiting the number of cytokine-producing cells.3 The enteric-coating of mycophenolic acid tablets prevents the development of upper gastrointestinal adverse events by delaying drug release until it reaches the small intestine.6 DB01025 Amlexanox small molecule approved 68302-57-8 298.2934 C16H14N2O4 P80511#Protein S100-A12@Q99584#Protein S100-A13@P08700#Interleukin-3@P05230#Fibroblast growth factor 1 Amlexanox is a mucoadhesive oral paste which has been clinically proven to abort the onset, accelerate healing and resolve the pain of aphthous ulcers (canker sores). It decreases the time ulcers take to heal. Because amlexanox decreases the healing time, it also decreases the pain you feel. Recent studies have also shown that the majority of ulcers can be prevented by application of the paste during the prodromal (pre-ulcerative) phase of the disease. Recurrent Aphthous Ulcers (RAU) also known as Recurrent Aphthous Stomatitis (RAS) is recognized as the most common oral mucosal disease known to man. Estimates suggest that 20% - 25% of the general population suffer at least one incidence of aphthous ulcers each year. Amlexanox is also being investigated for its anti-allergenic and anti-inflammatory properties. D0G5UB DB01026 Ketoconazole small molecule approved 65277-42-1 531.431 C26H28Cl2N4O4 Q16850#Lanosterol 14-alpha demethylase@P05093#Steroid 17-alpha-hydroxylase/17,20 lyase@P10275#Androgen receptor@P08686#Steroid 21-hydroxylase@Q12809#Potassium voltage-gated channel subfamily H member 2@O75469#Nuclear receptor subfamily 1 group I member 2@Q14994#Nuclear receptor subfamily 1 group I member 3 Ketoconazole, similarly to other azole antifungals, is a fungistatic agent which causes growth arrest in fungal cells thereby preventing growth and spread of the fungus throughout the body.11 D0B4IF DB01028 Methoxyflurane small molecule approved 76-38-0 164.966 C3H4Cl2F2O P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P42261#Glutamate receptor 1@P23415#Glycine receptor subunit alpha-1@Q09470#Potassium voltage-gated channel subfamily A member 1@P98194#Calcium-transporting ATPase type 2C member 1@P03886#NADH-ubiquinone oxidoreductase chain 1 Methoxyflurane is a general inhalation anesthetic used for induction and maintenance of general anesthesia. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. It does so by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential. D07SOO DB01029 Irbesartan small molecule approved 138402-11-6 428.5294 C25H28N6O P30556#Type-1 angiotensin II receptor@P05412#Transcription factor AP-1 Irbesartan is an angiotensin receptor blocker used to treat hypertension and diabetic nephropathy.7,8 It has a long duration of action as it is usually taken once daily and a wide therapeutic index as doses may be as low as 150mg daily but doses of 900mg/day were well tolerated in healthy human subjects.7,8,5 D00JAU DB01030 Topotecan small molecule approved 123948-87-8 421.4458 C23H23N3O5 Q06AK7#DNA topoisomerase 1@Q969P6#DNA topoisomerase I, mitochondrial Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the Camptotheca acuminata tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug. D02PMO DB01031 Ethinamate small molecule approved 126-52-3 167.205 C9H13NO2 P00918#Carbonic anhydrase 2@P00915#Carbonic anhydrase 1 Ethinamate is used to treat insomnia (trouble in sleeping). However, it has generally been replaced by other medicines for the treatment of insomnia. If ethinamate is used regularly (for example, every day) to help produce sleep, it is usually not effective for more than 7 days. Structurally, it does not resemble the barbiturates, but it shares many effects with this class of drugs; the depressant effects of ethinamate are, however, generally milder than those of most barbiturates. Continued and inappropriate use of ethinamate can lead to tolerance and physical dependence, with withdrawal symptoms very similar to those of the barbiturates. D0CK3G DB01032 Probenecid small molecule approved 57-66-9 285.359 C13H19NO4S Q4U2R8#Solute carrier family 22 member 6@Q9NSA0#Solute carrier family 22 member 11@Q8TCC7#Solute carrier family 22 member 8@Q96RD7#Pannexin-1@Q9NYV7#Taste receptor type 2 member 16 Probenecid is a uricosuric and renal tubular blocking agent and is used in combination with colchicine to treat chronic gouty arthritis when complicated by frequent, recurrent acute attacks of gout. It inhibits the reabsorption of urate at the proximal convoluted tubule, thus increasing the urinary excretion of uric acid and decreasing serum urate levels. Effective uricosuria reduces the miscible urate pool, retards urate deposition, and promotes resorption of urate deposits. At the proximal and distal tubles, probenecid competitively inhibits the secretion of many weak organic acids including penicillins, most cephalosporins, and some other β-lactam antibiotics. This results in an increase in the plasma concentrations of acidic drugs eliminated principally by renal secretion, but only a slight increase if the drug is eliminated mainly by filtration. Thus, the drug can be used for therapeutic advantages to increase concentrations of certain β-lactam antibiotics in the treatment of gonorrhea, neurosyphilis, or pelvic inflammatory disease (PID). D0L7FM DB01033 Mercaptopurine small molecule approved 50-44-2 152.177 C5H4N4S P00492#Hypoxanthine-guanine phosphoribosyltransferase@P20839#Inosine-5'-monophosphate dehydrogenase 1@P12268#Inosine-5'-monophosphate dehydrogenase 2 Mercaptopurine is one of a large series of purine analogues which interfere with nucleic acid biosynthesis and has been found active against human leukemias. It is an analogue of the purine bases adenine and hypoxanthine. It is not known exactly which of any one or more of the biochemical effects of mercaptopurine and its metabolites are directly or predominantly responsible for cell death. D09UZO DB01035 Procainamide small molecule approved 51-06-9 235.3253 C13H21N3O Q12809#Potassium voltage-gated channel subfamily H member 2@Q14524#Sodium channel protein type 5 subunit alpha@P26358#DNA (cytosine-5)-methyltransferase 1 Procainamide is an agent indicated for production of local or regional anesthesia and in the treatment of ventricular tachycardia occurring during cardiac manipulation, such as surgery or catheterization, or which may occur during acute myocardial infarction, digitalis toxicity, or other cardiac diseases. The mode of action of the antiarrhythmic effect of Procainamide appears to be similar to that of procaine and quinidine. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole. The sinoatrial node is, however, unaffected. D0U5SI DB01036 Tolterodine small molecule approved 124937-51-5 325.4876 C22H31NO P20309#Muscarinic acetylcholine receptor M3@P08172#Muscarinic acetylcholine receptor M2@P08912#Muscarinic acetylcholine receptor M5@P11229#Muscarinic acetylcholine receptor M1@P08173#Muscarinic acetylcholine receptor M4 Tolterodine is a competitive muscarinic receptor antagonist. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors. After oral administration, tolterodine is metabolized in the liver, resulting in the formation of the 5-hydroxymethyl derivative, a major pharmacologically active metabolite. The 5-hydroxymethyl metabolite, which exhibits an antimuscarinic activity similar to that of tolterodine, contributes significantly to the therapeutic effect. Both tolterodine and the 5-hydroxymethyl metabolite exhibit a high specificity for muscarinic receptors, since both show negligible activity or affinity for other neurotransmitter receptors and other potential cellular targets, such as calcium channels. Tolterodine has a pronounced effect on bladder function. The main effects of tolterodine are an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure, consistent with an antimuscarinic action on the lower urinary tract. D0BZ7W DB01037 Selegiline small molecule approved 14611-51-9 187.286 C13H17N P27338#Amine oxidase [flavin-containing] B@P21397#Amine oxidase [flavin-containing] A Dopamine is an essential chemical that occurs in many parts of the body. It is the premature degradation of dopamine that results in the symptoms of Parkinson's disease. Monoamine oxidase (MAO) is an enzyme which accelerates the breakdown of dopamine. Selegiline can prolong the effects of dopamine in the brain by preventing its breakdown through seletively blocking MAO-B. It also may prevent the removal of dopamine between nerve endings and enhance release of dopamine from nerve cells. D0S2UG DB01039 Fenofibrate small molecule approved 49562-28-9 360.831 C20H21ClO4 Q07869#Peroxisome proliferator-activated receptor alpha@O75469#Nuclear receptor subfamily 1 group I member 2@Q9NPA2#Matrix metalloproteinase-25 Fenofibrate is a fibrate that activates peroxisome proliferator activated receptor alpha (PPARα) to alter lipid metabolism and treat primary hypercholesterolemia, mixed dyslipidemia, and severe hypertriglyceridemia.8,11,12 Fenofibrate requires once daily dosing and has a half life of 19-27 hours so its duration of action is long.3,11,12 Fenofibrate capsules are given at a dose of 50-150mg daily so the therapeutic index is wide.12 Patients should be counselled about the risk of rhabdomyolysis, myopathy, and cholelithiasis when taking fibrates.11,12 D07XGR DB01041 Thalidomide small molecule approved 50-35-1 258.2295 C13H10N2O4 P35354#Prostaglandin G/H synthase 2@P01375#Tumor necrosis factor@P21802#Fibroblast growth factor receptor 2@P19838#Nuclear factor NF-kappa-B p105 subunit@Q96SW2#Protein cereblon@P02763#Alpha-1-acid glycoprotein 1@P19652#Alpha-1-acid glycoprotein 2 Thalidomide, originally developed as a sedative, is an immunomodulatory and anti-inflammatory agent with a spectrum of activity that is not fully characterized. However, thalidomide is believed to exert its effect through inhibiting and modulating the level of various inflammatory mediators, particularly tumor necrosis factor-alpha (TNF-a) and IL-6. 5 Additionally, thalidomide is also shown to inhibit basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), suggesting a potential anti-angiogenic application of thalidomide in cancer patients. 6 D0U7GK DB01042 Melphalan small molecule approved 148-82-3 305.2 C13H18Cl2N2O2 Melphalan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. D00FGO DB01043 Memantine small molecule approved 19982-08-2 179.3018 C12H21N Q05586#Glutamate receptor ionotropic, NMDA 1@P14416#D(2) dopamine receptor@P28472#Gamma-aminobutyric acid receptor subunit beta-3@Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B@P23415#Glycine receptor subunit alpha-1@O75311#Glycine receptor subunit alpha-3 General effects D01JEU DB01044 Gatifloxacin small molecule approved 112811-59-3 375.3941 C19H22FN3O4 P72525#DNA topoisomerase 4 subunit A@Q59961#DNA topoisomerase 4 subunit B D03CQE DB01045 Rifampicin small molecule approved 13292-46-1 822.9402 C43H58N4O12 P0A8V2#DNA-directed RNA polymerase subunit beta@O75469#Nuclear receptor subfamily 1 group I member 2 Rifampin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency. DB01046 Lubiprostone small molecule approved 136790-76-6 390.468 C20H32F2O5 P51788#Chloride channel protein 2 Chronic idiopathic constipation is generally defined by infrequent or difficult passage of stool. The signs and symptoms associated with chronic idiopathic constipation (i.e., abdominal pain or discomfort, bloating, straining, and hard or lumpy stools) may be the result of abnormal colonic motility that can delay the transit of intestinal contents and impede the evacuation of rectal contents. One approach to the treatment of chronic idiopathic constipation is the secretion of fluid into the abdominal lumen through the activation of chloride channels in the apical membrane of the gastrointestinal epithelium. Lubiprostone is a locally acting chloride channel activator that increases intestinal chloride and fluid secretion without altering sodium and potassium concentrations in the serum. D00CTS DB01047 Fluocinonide small molecule approved 356-12-7 494.5249 C26H32F2O7 P04150#Glucocorticoid receptor@Q99835#Smoothened homolog Fluocinonide is a potent glucocorticoid steroid used topically as anti-inflammatory agent for the treatment of skin disorders such as eczema. It mediates its effects to relieve itching, redness, dryness, crusting, scaling, inflammation, and discomfort associated with inflammatory skin conditions. D03ZZK DB01048 Abacavir small molecule approved 136470-78-5 286.3323 C14H18N6O Q72547#Reverse transcriptase/RNaseH@P01889#HLA class I histocompatibility antigen, B-27 alpha chain Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Abacavir is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The concentration of drug necessary to effect viral replication by 50 percent (EC50) ranged from 3.7 to 5.8 μM (1 μM = 0.28 mcg/mL) and 0.07 to 1.0 μM against HIV-1IIIB and HIV-1BaL, respectively, and was 0.26 ± 0.18 μM against 8 clinical isolates. Abacavir had synergistic activity in cell culture in combination with the nucleoside reverse transcriptase inhibitor (NRTI) zidovudine, the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine, and the protease inhibitor (PI) amprenavir; and additive activity in combination with the NRTIs didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zalcitabine. D0A4IJ DB01050 Ibuprofen small molecule approved 15687-27-1 206.2808 C13H18O2 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1@P10415#Apoptosis regulator Bcl-2@P07204#Thrombomodulin@P12104#Fatty acid-binding protein, intestinal@P37231#Peroxisome proliferator-activated receptor gamma@P13569#Cystic fibrosis transmembrane conductance regulator@Q07869#Peroxisome proliferator-activated receptor alpha@P07359#Platelet glycoprotein Ib alpha chain@P31151#Protein S100-A7 Ibuprofen has multiple actions in different inflammatory pathways involved in acute and chronic inflammation. The main effects reported in ibuprofen are related to the control of pain, fever and acute inflammation by the inhibition of the synthesis of prostanoids by COX-1 and COX-2. Pain relief is attributed to peripheral affected regions and central nervous system effects in the pain transmission mediated by the dorsal horn and higher spinothalamic tract. Some reports have tried to link the pain regulation with a possible enhancement on the synthesis of endogenous cannabinoids and action on the NMDA receptors. The effect on pain has been shown to be related to the cortically evoked potentials.23 D0R1QE DB01051 Novobiocin small molecule approved 303-81-1 612.6243 C31H36N2O11 P0A4L9#DNA gyrase subunit B@Q06AK7#DNA topoisomerase 1 Novobiocin is an aminocoumarin antibiotic that was produced by the actinomycete Streptomyces niveus. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. Other antibiotics in the aminocoumarin class include coumermycin A1 and clorobiocin. D0Q0PR DB01053 Benzylpenicillin small molecule approved 61-33-6 334.39 C16H18N2O4S Q8TCC7#Solute carrier family 22 member 8@P46059#Solute carrier family 15 member 1@Q16348#Solute carrier family 15 member 2 Penicillin G is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Penicillin G has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of penicillin G results from the inhibition of cell wall synthesis and is mediated through penicillin G binding to penicillin binding proteins (PBPs). Penicillin G is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. D00QAR DB01054 Nitrendipine small molecule approved 39562-70-4 360.3612 C18H20N2O6 Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@P54289#Voltage-dependent calcium channel subunit alpha-2/delta-1@Q08289#Voltage-dependent L-type calcium channel subunit beta-2@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@Q9NY47#Voltage-dependent calcium channel subunit alpha-2/delta-2@O95180#Voltage-dependent T-type calcium channel subunit alpha-1H Nitrendipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nitrendipine is similar to other peripheral vasodilators. Nitrendipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. D0A1DH DB01056 Tocainide small molecule approved 41708-72-9 192.2575 C11H16N2O Q14524#Sodium channel protein type 5 subunit alpha Tocainide is a primary amine analog of lidocaine with antiarrhythmic properties useful in the treatment of ventricular arrhythmias. Tocainide, like lidocaine, produces dose dependent decreases in sodium and potassium conductance, thereby decreasing the excitability of myocardial cells. In experimental animal models, the dose-related depression of sodium current is more pronounced in ischemic tissue than in normal tissue. Tocainide is a Class I antiarrhythmic compound with electrophysiologic properties in man similar to those of lidocaine, but dissimilar from quinidine, procainamide, and disopyramide. D01PJR DB01057 Echothiophate small molecule approved 6736-03-4 256.323 C9H23NO3PS P06276#Cholinesterase Echothiophate Iodide is a potent, long-acting cholinesterase inhibitor used as a miotic in the treatment of glaucoma. Echothiophate iodide will depress both plasma and erythrocyte cholinesterase levels in most patients after a few weeks of eyedrop therapy. DB01058 Praziquantel small molecule approved 55268-74-1 312.4061 C19H24N2O2 Praziquantel is an anthelmintic used in most schistosome and many cestode infestations. Praziquantel effects the permeability of the cell membrane resulting in the contraction of schistosomes. The drug further causes vacuolization and disintegration of the schistosome tegument. The effect is more marked on adult worms compared to young worms. An increased calcium influx may play an important role. Secondary effects are inhibition of glucose uptake, lowering of glycogen levels and stimulation of lactate release. The action of praziquantel is limited very specifically to trematodes and cestodes; nematodes (including filariae) are not affected. D0L9ZR DB01059 Norfloxacin small molecule approved 70458-96-7 319.3308 C16H18FN3O3 P11388#DNA topoisomerase 2-alpha@P05653#DNA gyrase subunit A@P0C1U9#DNA topoisomerase 4 subunit A Norfloxacin is a quinolone/fluoroquinolone antibiotic. Norfloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. D0Q2PE DB01060 Amoxicillin small molecule approved 26787-78-0 365.404 C16H19N3O5S Q8L103#Penicillin binding protein Amoxicillin competitively inhibit penicillin binding proteins, leading to upregulation of autolytic enzymes and inhibition of cell wall synthesis.9,10,5 Amoxicillin has a long duration of action as it is usually given twice daily.15 Amoxicillin has a wide therapeutic range as mild overdoses are not associated with significant toxicity.14 Patients should be counselled regarding the risk of anaphylaxis, Clostridium difficile infections, and bacterial resistance.17 D0F6EO DB01061 Azlocillin small molecule approved 37091-66-0 461.492 C20H23N5O6S Similar to mezlocillin and piperacillin, azlocillin is an acylampicillin that exhibits an extended-spectrum of activity and in vitro potency that is greater than that of the carboxy penicillins. Azlocillin is shown to be effective against a broad spectrum of bacteria, including Pseudomonas aeruginosa and enterococci. D0PA2N DB01062 Oxybutynin small molecule approved 5633-20-5 357.4864 C22H31NO3 P20309#Muscarinic acetylcholine receptor M3@P08172#Muscarinic acetylcholine receptor M2@P11229#Muscarinic acetylcholine receptor M1 Oxybutynin exerts antispasmodic actions on the bladder, relieving the uncomfortable symptoms of overactive bladder, including urinary urgency and frequency. These actions occur through the inhibition of muscarinic receptors. DB01063 Acetophenazine small molecule approved 2751-68-0 411.56 C23H29N3O2S P10275#Androgen receptor@P14416#D(2) dopamine receptor Acetophenzine is a phenothiazine antipsychotic intended for the management of schizophrenia and other psychotic disorders. D0L0MB DB01064 Isoprenaline small molecule approved 7683-59-2 211.2576 C11H17NO3 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P00441#Superoxide dismutase [Cu-Zn] Isoprenaline is a non-selective beta adrenergic receptor agonist used in a number of indications for the heart, as well as bronchospasm in anesthesia.2,14 Isoprenaline has a short duration of action as it is rapidly cleared,8,7 and a wide therapeutic index.14 Patients should be counselled regarding the risks of isoprenaline in the treatment of cardiogenic shock following myocardial infarction, paradoxical worsening of heart block, or precipitation of Adams-Stokes attacks.14 DB01065 Melatonin small molecule approved 73-31-4 232.2783 C13H16N2O2 P48039#Melatonin receptor type 1A@P49286#Melatonin receptor type 1B@Q92753#Nuclear receptor ROR-beta@P0DP23#Calmodulin@P05164#Myeloperoxidase@P11678#Eosinophil peroxidase@P27797#Calreticulin@P46597#Acetylserotonin O-methyltransferase@P16083#Ribosyldihydronicotinamide dehydrogenase [quinone] Melatonin is a hormone normally produced in the pineal gland and released into the blood. The essential amino acid L-tryptophan is a precursor in the synthesis of melatonin. It helps regulate sleep-wake cycles or the circadian rhythm. Production of melatonin is stimulated by darkness and inhibited by light. High levels of melatonin induce sleep and so consumption of the drug can be used to combat insomnia and jet lag. D0AN7B DB01066 Cefditoren small molecule approved 104145-95-1 506.578 C19H18N6O5S3 P0A3M6#Penicillin-binding protein 2B Cefditoren pivoxil is a prodrug which is hydrolyzed by esterases during absorption, and the drug is distributed in the circulating blood as active cefditoren. Cefditoren is a cephalosporin with antibacterial activity against gram-positive and gram-negative pathogens. Cefditoren is effective against Staphylococcus aureus (methicillin-susceptible strains, including b-lactamase-producing strains), penicillin-susceptible strains of Staphylococcus aureus and Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae (including b-lactamase-producing strains), Haemophilus parainfluenzae (including b-lactamase-producing strains), Moraxella catarrhalis (including b-lactamase-producing strains), Streptococcus agalactiae, Streptococcus Groups C and G, and Streptococcus, viridans group (penicillin-susceptible and -intermediate strains). D0E3RW DB01067 Glipizide small molecule approved 29094-61-9 445.535 C21H27N5O4S P37231#Peroxisome proliferator-activated receptor gamma D0Z4SB DB01068 Clonazepam small molecule approved 1622-61-3 315.711 C15H10ClN3O3 O75469#Nuclear receptor subfamily 1 group I member 2@P28472#Gamma-aminobutyric acid receptor subunit beta-3 The pharmacodynamic properties of clonazepam are common among benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects 6,11,12,13. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absence seizures (petit mal), slow spike wave, generalized spike wave, spikes with temporal or other locations, as well as irregular spikes and waves Label 6,11,12,13. Moreover, the agent can also decrease the frequency, amplitude, duration, and spread of discharge in minor motor seizures Label 12. D0CP4E DB01069 Promethazine small molecule approved 60-87-7 284.419 C17H20N2S P70174#Histamine H1 receptor@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5@P0DP23#Calmodulin@P25021#Histamine H2 receptor Promethazine is is a histamine H1 antagonist that can be used for it's ability to induce sedation, reduce pain, and treat allergic reactions.12 Promethazine's effects generally last 4-6h but can last up to 12h.12 Patients should be counselled regarding CNS and respiratory depression, reduce seizure threshold, and bone marrow depression.12 D0T2XU DB01070 Dihydrotachysterol small molecule approved 67-96-9 398.6642 C28H46O P11473#Vitamin D3 receptor Dihydrotachysterol is hydroxylated in the liver to 25-hydroxydihydrotachysterol, which is the major circulating active form of the drug. It does not undergo further hydroxylation by the kidney and therefore is the analogue of 1, 25-dihydroxyvitamin D. Dihydrotachysterol is effective in the elevation of serum calcium by stimulating intestinal calcium absorption and mobilizing bone calcium in the absence of parathyroid hormone and of functioning renal tissue. Dihydrotachysterol also increases renal phosphate excretion. D0G8OC DB01072 Atazanavir small molecule approved 198904-31-3 704.8555 C38H52N6O7 Atazanavir (ATV) is an azapeptide HIV-1 protease inhibitor (PI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Atazanavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. Atazanivir is pharmacologically related but structurally different from other protease inhibitors and other currently available antiretrovirals. D07IQS DB01073 Fludarabine small molecule approved 21679-14-1 285.235 C10H12FN5O4 P27707#Deoxycytidine kinase@P09884#DNA polymerase alpha catalytic subunit@P23921#Ribonucleoside-diphosphate reductase large subunit Fludarabine is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It acts at DNA polymerase alpha, ribonucleotide reductase and DNA primase, results in the inhibition of DNA synthesis, and destroys the cancer cells. D0F2XQ DB01074 Perhexiline small molecule approved 6621-47-2 277.4879 C19H35N P50416#Carnitine O-palmitoyltransferase 1, liver isoform@P23786#Carnitine O-palmitoyltransferase 2, mitochondrial@Q12809#Potassium voltage-gated channel subfamily H member 2 Used in the treatment of unresponsive or refractory angina. Perhexiline increases glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Perhexiline also potentiates platelet responsiveness to nitric oxide both in patients with angina and patients with acute coronary syndrome. The predominant mechanism of this particular perhexiline effect is an increase in platelet cGMP responsiveness. Perhexiline also may reduce the potential for nitric oxide clearance by neutrophil-derived oxygen. Perhexiline relieves symptoms of angina, improves exercise tolerance, and increases the workload needed to induce ischaemia when used as monotherapy. The primary therapeutic roles for perhexiline are as short-term therapy (less than 3 months duration) in patients with severe ischaemia awaiting coronary revascularisation or long-term therapy in patients with ischaemic symptoms refractory to other therapeutic measures. D00SBN DB01075 Diphenhydramine small molecule approved 58-73-1 255.3547 C17H21NO P70174#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2 Diphenhydramine has anti-histaminic (H1-receptor), anti-emetic, anti-vertigo and sedative and hypnotic properties 12. The anti-histamine action occurs by blocking the spasmogenic and congestive effects of histamine by competing with histamine for H1 receptor sites on effector cells, preventing but not reversing responses mediated by histamine alone 12. Such receptor sites may be found in the gut, uterus, large blood vessels, bronchial muscles, and elsewhere 12. Anti-emetic action is by inhibition at the medullary chemoreceptor trigger zone 12. Anti-vertigo action is by a central antimuscarinic effect on the vestibular apparatus and the integrative vomiting center and medullary chemoreceptor trigger zone of the midbrain 12. D01FGR DB01076 Atorvastatin small molecule approved 134523-00-5 558.6398 C33H35FN2O5 P04035#3-hydroxy-3-methylglutaryl-coenzyme A reductase@P27487#Dipeptidyl peptidase 4@Q92769#Histone deacetylase 2@Q14994#Nuclear receptor subfamily 1 group I member 3 D01QIN DB01077 Etidronic acid small molecule approved 2809-21-4 206.0282 C2H8O7P2 Q13332#Receptor-type tyrosine-protein phosphatase S@P38606#V-type proton ATPase catalytic subunit A@P12235#ADP/ATP translocase 1@P05141#ADP/ATP translocase 2@P12236#ADP/ATP translocase 3 Etidronic acid is a first generation bisphosphonate that inhibits the action of osteoclasts, preventing bone resporption.7 It has a wide therapeutic index as overdoses are not associated with severe toxicity and a long duration of action as it slowly releases from the bone.7 Patients should be counselled regarding the risk of upper gastrointestinal adverse reactions.7 D00NNC DB01078 Deslanoside small molecule approved 17598-65-1 943.0791 C47H74O19 P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Deslanoside is a cardiac glycoside used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation. D07TGN DB01079 Tegaserod small molecule approved 145158-71-0 301.394 C16H23N5O Q13639#5-hydroxytryptamine receptor 4@P28335#5-hydroxytryptamine receptor 2C@P28223#5-hydroxytryptamine receptor 2A@P41595#5-hydroxytryptamine receptor 2B In general, it has been determined that tegaserod is an agonist of serotonin type-4 (5-HT(4)) receptors, an antagonist at 5-HT(2B) receptors, but is expected to possess minimal binding to 5-HT(1) receptors, and virtually no affinity for 5-HT(3) or dopamine receptors 1,3,6. D00XWD DB01080 Vigabatrin small molecule approved 68506-86-5 129.157 C6H11NO2 P80404#4-aminobutyrate aminotransferase, mitochondrial Vigabatrin is an antiepileptic agent chemically unrelated to other anticonvulsants. Vigabatrin prevents the metabolism of GABA by irreversibly inhibiting GABA transaminase (GABA-T). As vigabatrin is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), its duration of effect is thought to be dependent on the rate of GABA-T re-synthesis rather than on the rate of drug elimination.7 D0R3QY DB01081 Diphenoxylate small molecule approved 915-30-0 452.5873 C30H32N2O2 P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor Diphenoxylate, an antidiarrheal, is effective as adjunctive therapy in the management of diarrhea. Diphenoxylate is rapidly and extensively metabolized in man by ester hydrolysis to diphenoxylic acid (difenoxine), which is biologically active and the major metabolite in the blood. D0J2TN DB01082 Streptomycin small molecule approved 57-92-1 581.5741 C21H39N7O12 P0A7S3#30S ribosomal protein S12@Q9UM07#Protein-arginine deiminase type-4 Although streptomycin originally had broad gram-negative and gram-positive coverage, its spectrum of activity has been significantly narrowed due to antibiotic resistance.2 Streptomycins current spectrum of activity includes susceptible strains of Yersinia pestis, Francisella tularensis, Brucella, Calymmatobacterium granulomatis, H. ducreyi, H. influenza, K. pneumoniae pneumonia, E.coli, Proteus, A. aerogenes, K. pneumoniae, Enterococcus faecalis, Streptococcus viridans, Enterococcus faecalis, and Gram-negative bacillary bacteremia. Streptomycin is not reliably active against pseudomonas aeruginosa.2 D0N0EQ DB01083 Orlistat small molecule approved 96829-58-2 495.7348 C29H53NO5 P16233#Pancreatic triacylglycerol lipase@P07098#Gastric triacylglycerol lipase@P49327#Fatty acid synthase Orlistat helps with weight reduction and maintenance by inhibiting the absorption of dietary fats via the inhibition of lipase enzymes.9,10 D0T9TJ DB01084 Emedastine small molecule approved 87233-61-2 302.4145 C17H26N4O P70174#Histamine H1 receptor Emedastine is a relatively selective H1-receptor antagonist. D02XJI DB01085 Pilocarpine small molecule approved 92-13-7 208.2569 C11H16N2O2 P20309#Muscarinic acetylcholine receptor M3@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P08173#Muscarinic acetylcholine receptor M4 Pilocarpine is a choline ester miotic and a positively charged quaternary ammonium compound. Pilocarpine, in appropriate dosage, can increase secretion by the exocrine glands. The sweat, salivary, lacrimal, gastric, pancreatic, and intestinal glands and the mucous cells of the respiratory tract may be stimulated. When applied topically to the eye as a single dose it causes miosis, spasm of accommodation, and may cause a transitory rise in intraocular pressure followed by a more persistent fall. Dose-related smooth muscle stimulation of the intestinal tract may cause increased tone, increased motility, spasm, and tenesmus. Bronchial smooth muscle tone may increase. The tone and motility of urinary tract, gallbladder, and biliary duct smooth muscle may be enhanced. Pilocarpine may have paradoxical effects on the cardiovascular system. The expected effect of a muscarinic agonist is vasodepression, but administration of pilocarpine may produce hypertension after a brief episode of hypotension. Bradycardia and tachycardia have both been reported with use of pilocarpine. D06HLY DB01086 Benzocaine small molecule approved 94-09-7 165.1891 C9H11NO2 Q9Y5Y9#Sodium channel protein type 10 subunit alpha Benzocaine is indicated for use as a topical anesthetic.4 It has a duration of action of approximately 10 minutes9 and a wide therapeutic window.4 Patients should be counselled regarding the risks of methemoglobinemia.4,5,6,8 D0Q8ZX DB01087 Primaquine small molecule approved 90-34-6 259.3467 C15H21N3O P08729#Keratin, type II cytoskeletal 7@P16083#Ribosyldihydronicotinamide dehydrogenase [quinone] Primaquine is an antimalarial agent and is the essential co-drug with chloroquine in treating all cases of malaria. In the blood, malaria parasites break down a part of the red blood cells known as haemoglobin. When this happens haemoglobin is divided into two parts; haem and globin. Haem is toxic to the malaria parasite. To prevent it from being damaged, the malaria parasite produces an chemical which converts the toxic haem into a non-toxic product. Primaquine acts by interfering with a part of the parasite (mitochondria) that is responsible for supplying it with energy. Without energy the parasite dies. This stops the infection from continuing and allows the person to recover. Primaquine kills the intrahepatic form of Plasmodium vivax and Plasmodium ovale, and thereby prevents the development of the erythrocytic forms that are responsible for relapses (it also kills gametocytes). Primaquine is not used in the prevention of malaria, only in the treatment. It has insignificant activity against the asexual blood forms of the parasite and therefore it is always used in conjunction with a blood schizonticide and never as a single agent. Primaquine has gametocytocidal activity against all plasmodia, including P. falciparum. D0T1LK DB01088 Iloprost small molecule approved 78919-13-8 360.494 C22H32O4 P43119#Prostacyclin receptor@P34995#Prostaglandin E2 receptor EP1 subtype@P27815#cAMP-specific 3',5'-cyclic phosphodiesterase 4A@Q07343#cAMP-specific 3',5'-cyclic phosphodiesterase 4B@Q08493#cAMP-specific 3',5'-cyclic phosphodiesterase 4C@Q08499#cAMP-specific 3',5'-cyclic phosphodiesterase 4D@P00750#Tissue-type plasminogen activator@Q9Y5Y4#Prostaglandin D2 receptor 2 Iloprost is a synthetic analogue of prostacyclin PGI2 that dilates systemic and pulmonary arterial vascular beds. It was shown to affect platelet aggregation, but whether this effect contributes to its vasodilatory action has not been elucidated. There are two diastereoisomers of iloprost and the 4S isomer is reported to exhibit a higher potency in dilating blood vessels compared to the 4R isomer. D05ZTH DB01089 Deserpidine small molecule approved 131-01-1 578.6527 C32H38N2O8 Q05940#Synaptic vesicular amine transporter Deserpidine, an alkaloid of Rauwolfia canescens, is used as an antihypertensive. Rauwolfia alkaloids work by controlling nerve impulses along certain nerve pathways. As a result, they act on the heart and blood vessels to lower blood pressure. D09HDR DB01090 Pentolinium small molecule approved 144-44-5 240.428 C15H32N2 P32297#Neuronal acetylcholine receptor subunit alpha-3@P30926#Neuronal acetylcholine receptor subunit beta-4@Q9GZZ6#Neuronal acetylcholine receptor subunit alpha-10 Pentolinium acts as a ganglionic blocking agent. Pentolinium inhibits release of adrenaline and noradrenaline from adrenergic nerves. It is used as an antihypertensive, and can be administered orally, intramuscularly, and subcutaneously. D0IX1A DB01091 Butenafine small molecule approved 101828-21-1 317.4672 C23H27N Q92206#Squalene monooxygenase Butenafine is a synthetic antifungal agent that is structurally and pharmacologically related to allylamine antifungals. The exact mechanism of action has not been established, but it is suggested that butenafine's antifungal activity is exerted through the alteration of cellular membranes, which results in increased membrane permeability, and growth inhibition. Butenafine is mainly active against dermatophytes and has superior fungicidal activity against this group of fungi when compared to that of terbinafine, naftifine, tolnaftate, clotrimazole, and bifonazole. It is also active against Candida albicans and this activity is superior to that of terbinafine and naftifine. Butenafine also generates low MICs for Cryptococcus neoformans and Aspergillus spp. as well. D0B4DC DB01092 Ouabain small molecule approved 630-60-4 584.6525 C29H44O12 P05023#Sodium/potassium-transporting ATPase subunit alpha-1@P50993#Sodium/potassium-transporting ATPase subunit alpha-2@P13637#Sodium/potassium-transporting ATPase subunit alpha-3 Ouabain, a cardiac glycoside similar to digitoxin, is used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation. DB01093 Dimethyl sulfoxide small molecule approved 67-68-5 78.133 C2H6OS Q01344#Interleukin-5 receptor subunit alpha@P01106#Myc proto-oncogene protein Dimethyl Sulfoxide may have anti-inflammatory, antioxidant and analgesic activities. Dimethyl Sulfoxide also readily penetrates cellular membranes. The membrane-penetrating ability of dimethyl sulfoxide may enhance diffusion of other substances through the skin. For this reason, mixtures of idoxuridine and dimethyl sulfoxide have been used for topical treatment of herpes zoster in the United Kingdom. DB01095 Fluvastatin small molecule approved 93957-54-1 411.4659 C24H26FNO4 P04035#3-hydroxy-3-methylglutaryl-coenzyme A reductase@Q92769#Histone deacetylase 2 Fluvastatin, the first synthetically-derived HMG-CoA reductase inhibitor, is a hydrophilic, acidic, antilipemic agent used to lower cholesterol and triglyceride levels associated with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb), to slow the progression of coronary atherosclerosis in patients with CHD and as secondary prevention therapy in patients with CHD to reduce the risk of requiring coronary revascularization procedures. Although similar to lovastatin, simvastatin, and pravastatin, fluvastatin has a shorter half-life, no active metabolites, extensive protein binding, and minimal CSF penetration. Fluvastatin acts primarily in the liver. It is prepared as a racemate of two erythro enantiomers of which the 3R,5S enantiomer exerts the pharmacologic effect. D08GHB DB01096 Oxamniquine small molecule approved 21738-42-1 279.3348 C14H21N3O3 Oxamniquine is an anthelmintic with schistosomicidal activity against Schistosoma mansoni, but not against other Schistosoma spp. Oxamniquine causes worms to shift from the mesenteric veins to the liver where the male worms are retained; the female worms return to the mesentery, but can no longer release egg. D0P4MT DB01097 Leflunomide small molecule approved 75706-12-6 270.2073 C12H9F3N2O2 P35869#Aryl hydrocarbon receptor@Q14289#Protein-tyrosine kinase 2-beta Leflunomide is a pyrimidine synthesis inhibitor indicated in adults for the treatment of active rheumatoid arthritis (RA). RA is an auto-immune disease characterized by high T-cell activity. T cells have two pathways to synthesize pyrimidines: the salvage pathways and the de novo synthesis. At rest, T lymphocytes meet their metabolic requirements by the salvage pathway. Activated lymphocytes need to expand their pyrimidine pool 7- to 8-fold, while the purine pool is expanded only 2- to 3-fold. To meet the need for more pyrimidines, activated T cells use the de novo pathway for pyrimidine synthesis. Therefore, activated T cells, which are dependent on de novo pyrimidine synthesis, will be more affected by leflunomide's inhibition of dihydroorotate dehydrogenase than other cell types that use the salvage pathway of pyrimidine synthesis. D08ROP DB01098 Rosuvastatin small molecule approved 287714-41-4 481.538 C22H28FN3O6S P04035#3-hydroxy-3-methylglutaryl-coenzyme A reductase@P20701#Integrin alpha-L Rosuvastatin is a synthetic, enantiomerically pure antilipemic agent. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.15,21 D0JE2E DB01099 Flucytosine small molecule approved 2022-85-7 129.0925 C4H4FN3O P04818#Thymidylate synthase Flucytosine is an antimetabolite that acts as an antifungal agent with in vitro and in vivo activity against Candida and Cryptococcus. Flucytosine enters the fungal cell via cytosine permease; thus, flucytosine is metabolized to 5-fluorouracil within fungal organisms. The 5-fluorouracil is extensively incorporated into fungal RNA and inhibits synthesis of both DNA and RNA. The result is unbalanced growth and death of the fungal organism. Antifungal synergism between Ancobon and polyene antibiotics, particularly amphotericin B, has been reported. D0S5WG DB01100 Pimozide small molecule approved 2062-78-4 461.5462 C28H29F2N3O Q12809#Potassium voltage-gated channel subfamily H member 2@P0DP23#Calmodulin@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor Pimozide is an orally active antipsychotic drug product which shares with other antipsychotics the ability to blockade dopaminergic receptors on neurons in the central nervous system. However, receptor blockade is often accompanied by a series of secondary alterations in central dopamine metabolism and function which may contribute to both pimozide's therapeutic and untoward effects. In addition, pimozide, in common with other antipsychotic drugs, has various effects on other central nervous system receptor systems which are not fully characterized. Pimozide also has less potential for inducing sedation and hypotension as it has more specific dopamine receptor blocking activity than other neuroleptic agents (and is therefore a suitable alternative to haloperidol). D00KHM DB01101 Capecitabine small molecule approved 154361-50-9 359.3501 C15H22FN3O6 P04818#Thymidylate synthase Capecitabine is a fluoropyrimidine carbamate with antineoplastic activity indicated for the treatment of metastatic breast cancer and colon cancer. It is an orally administered systemic prodrug that has little pharmacologic activity until it is converted to fluorouracil by enzymes that are expressed in higher concentrations in many tumors. Fluorouracil it then metabolized both normal and tumor cells to 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). D00HCQ DB01102 Arbutamine small molecule approved 128470-16-6 317.3795 C18H23NO4 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor Not Available D06KYN DB01104 Sertraline small molecule approved 79617-96-2 306.23 C17H17Cl2N P31645#Sodium-dependent serotonin transporter@Q01959#Sodium-dependent dopamine transporter@P23975#Sodium-dependent noradrenaline transporter@Q7RTT9#Equilibrative nucleoside transporter 4 Sertraline improves or relieves the symptoms of depression, OCD, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder via the inhibition of serotonin reuptake.10,21 Clinical studies have shown that it improves cognition in depressed patients.6 It has less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because it does not exert significant anticholinergic, antihistamine, or adrenergic (alpha1, alpha2, beta) blocking activity.5 The onset of action and beneficial effects are usually noticed after 4-6 weeks, for reasons that are not fully understood and currently under investigation.17,27 D0K0TC DB01105 Sibutramine small molecule approved 106650-56-0 279.848 C17H26ClN Q01959#Sodium-dependent dopamine transporter@P31645#Sodium-dependent serotonin transporter@P23975#Sodium-dependent noradrenaline transporter Sibutramine is an orally administered agent for the treatment of obesity. Sibutramine exerts its pharmacological actions predominantly via its secondary (M1) and primary (M2) amine metabolites. The parent compound, sibutramine, is a potent inhibitor of serotonin and norepinephrine reuptake in vivo, but not in vitro. However, metabolites M1 and M2 inhibit the reuptake of these neurotransmitters both in vitro and in vivo. In human brain tissue, M1 and M2 also inhibit dopamine reuptake in vitro, but with ~3-fold lower potency than for the reuptake inhibition of serotonin or norepinephrine. Sibutramine, M1 and M2 exhibit no evidence of anticholinergic or antihistaminergic actions. In addition, receptor binding profiles show that sibutramine, M1 and M2 have low affinity for serotonin (5-HT1, 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C), norepinephrine (b, b1, b3, a1 and a2), dopamine (D1 and D2), benzodiazepine, and glutamate (NMDA) receptors. These compounds also lack monoamine oxidase inhibitory activity in vitro and in vivo. D08KVZ DB01106 Levocabastine small molecule approved 79516-68-0 420.528 C26H29FN2O2 P70174#Histamine H1 receptor@O95665#Neurotensin receptor type 2 Levocabastine is a selective histamine H1-receptor antagonist exerting inhibitory effects on the release of chemical mediators from mast cells and on the chemotaxis of polymorphonuclear leukocytes and eosinophils. Both histamine and antigens induced conjunctivitis can be inhibited by levocabastine. Levocabastine can also reduce symptoms of allergic rhinitis by preventing an increase in vascular permeability of nasal mucosa. D08SEI DB01107 Methyprylon small molecule approved 125-64-4 183.2475 C10H17NO2 P14867#Gamma-aminobutyric acid receptor subunit alpha-1 Methyprylon, a piperidinedione CNS depressant, is close to barbituric acid in structure, but different enough to be called a "non-barbiturate" sedative-hynotic. Methyprylon is used for insomnia and daytime tension. Methyprylon depresses the activity of muscle tissues, the heart, and the respiratory system. D05OQJ DB01108 Trilostane small molecule approved 13647-35-3 329.4333 C20H27NO3 P14060#3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1@P26439#3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2@Q92731#Estrogen receptor beta Trilostane blocks an enzyme involved in the production of several steroids including cortisol. Inhibiting this enzyme inhibits the production of cortisol. In Cushing's syndrome, the adrenal gland overproduces steroids. Although steroids are important for various functions of the body, too much can cause problems. Trilostane reduces the amount of steroids produced by the adrenal gland. This product was withdrawn from the U.S. market in April 1994. D03XOC DB01110 Miconazole small molecule approved 22916-47-8 416.129 C18H14Cl4N2O P29474#Nitric oxide synthase, endothelial@P35228#Nitric oxide synthase, inducible@O75469#Nuclear receptor subfamily 1 group I member 2 Miconazole is an azole antifungal that functions primarily through inhibition of a specific demethylase within the CYP450 complex.3 As miconazole is typically applied topically and is minimally absorbed into the systemic circulation following application, the majority of patient reactions are limited to hypersensitivity and cases of anaphylaxis.13 Patients using intravaginal miconazole products are advised not to rely on contraceptives to prevent pregnancy and sexually transmitted infections, as well as not to use tampons concurrently.15 D00AXJ DB01111 Colistimethate small molecule approved 12705-41-8 1634.87 C58H105N16O28S5 Colistimethate is a polymyxin antibiotic agent. Originally, colistimethate sodium was thought to be less toxic than polymyxin B; however, if the drugs are administered at comparable doses, their toxicities may be similar. Polymyxins are cationic polypeptides that disrupt the bacterial cell membrane through a detergentlike mechanism. With the development of less toxic agents, such as extended-spectrum penicillins and cephalosporins, parenteral polymyxin use was largely abandoned, except for the treatment of multidrug-resistant pulmonary infections in patients with cystic fibrosis. More recently, however, the emergence of multidrug-resistant gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii, and the lack of new antimicrobial agents have led to the revived use of the polymyxins. D0Q3BV DB01112 Cefuroxime small molecule approved 55268-75-2 424.385 C16H16N4O8S Cefuroxime is a β-lactam type antibiotic. More specifically, it is a second-generation cephalosporin. Cephalosporins work the same way as penicillins: they interfere with the peptidoglycan synthesis of the bacterial wall by inhibiting the final transpeptidation needed for the cross-links. This effect is bactericidal. Cefuroxime is effective against the following organisms: Aerobic Gram-positive Microorganisms: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes. Aerobic Gram-negative Microorganisms: Escherichia coli, Haemophilus influenzae (including beta-lactamase-producing strains), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis (including beta-lactamase-producing strains), Neisseria gonorrhoeae (including beta-lactamase-producing strains). Spirochetes: Borrelia burgdorferi. Cefuroxime axetil is the prodrug D0Y2IE DB01113 Papaverine small molecule approved 58-74-2 339.385 C20H21NO4 Q07343#cAMP-specific 3',5'-cyclic phosphodiesterase 4B@Q9Y233#cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Papaverine is a nonxanthine phosphodiesterase inhibitor for the relief of cerebral and peripheral ischemia associated with arterial spasm and myocardial ischemia complicated by arrhythmias. The main actions of Papaverine are exerted on cardiac and smooth muscle. Like qathidine, Papaverine acts directly on the heart muscle to depress conduction and prolong the refractory period. Papaverine relaxes various smooth muscles. This relaxation may be prominent if spasm exists. The muscle cell is not paralyzed by Papaverine and still responds to drugs and other stimuli causing contraction. The antispasmodic effect is a direct one, and unrelated to muscle innervation. Papaverine is practically devoid of effects on the central nervous system. Papaverine relaxes the smooth musculature of the larger blood vessels, especially coronary, systemic peripheral, and pulmonary arteries. D0NJ3V DB01114 Chlorpheniramine small molecule approved 132-22-9 274.788 C16H19ClN2 P70174#Histamine H1 receptor@P31645#Sodium-dependent serotonin transporter@P23975#Sodium-dependent noradrenaline transporter@Q01959#Sodium-dependent dopamine transporter In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Chlorpheniramine, is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. D0B7NG DB01115 Nifedipine small molecule approved 21829-25-4 346.3346 C17H18N2O6 Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q08289#Voltage-dependent L-type calcium channel subunit beta-2@O75469#Nuclear receptor subfamily 1 group I member 2@P0DP23#Calmodulin@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@Q9UK17#Potassium voltage-gated channel subfamily D member 3 Nifedipine is an inhibitor of L-type voltage gated calcium channels that reduces blood pressure and increases oxygen supply to the heart.1 Immediate release nifedipine's duration of action requires dosing 3 times daily.13 Nifedipine dosing is generally 10-120mg daily.13 Patients should be counselled regarding the risk of excessive hypotension, angina, and myocardial infarction.13 D04OSE DB01116 Trimethaphan small molecule approved 7187-66-8 365.512 C22H25N2OS Q9GZZ6#Neuronal acetylcholine receptor subunit alpha-10 Trimethaphan is indicated for production of controlled hypotension during surgery to reduce bleeding into the surgical field and also for rapid reduction of blood pressure in the treatment of hypertensive emergencies, especially in patients with acute dissecting aneurysm, and in the emergency treatment of pulmonary edema in patients with pulmonary hypertension associated with systemic hypertension. D0B6CC DB01117 Atovaquone small molecule approved 95233-18-4 366.837 C22H19ClO3 Q02127#Dihydroorotate dehydrogenase (quinone), mitochondrial@Q08210#Dihydroorotate dehydrogenase (quinone), mitochondrial Atovaquone is a highly lipophilic drug that closely resembles the structure [ubiquinone]. Its inhibitory effect being comparable to ubiquinone, atovaquone can act by selectively affecting mitochondrial electron transport and parallel processes such as ATP and pyrimidine biosynthesis in atovaquone-responsive parasites. Cytochrome bc1 complex (complex III) seems to serve as a highly discriminating molecular target for atovaquone in Plasmodia. There is no significant risk for myelosuppression associated with atovaquone, making this drug a beneficial therapeutic agent for recipients of bone marrow transplantation. D06ZEE DB01118 Amiodarone small molecule approved 1951-25-3 645.3116 C25H29I2NO3 Q9P0X4#Voltage-dependent T-type calcium channel subunit alpha-1I@P37231#Peroxisome proliferator-activated receptor gamma@Q07869#Peroxisome proliferator-activated receptor alpha@Q86YN6#Peroxisome proliferator-activated receptor gamma coactivator 1-beta After intravenous administration, amiodarone acts to relax smooth muscles that line vascular walls, decreases peripheral vascular resistance (afterload), and increases the cardiac index by a small amount. Administration by this route also decreases cardiac conduction, preventing and treating arrhythmias.2,7,18 When it is given orally, however, amiodarone does not lead to significant changes in the left ventricular ejection fraction. Similar to other anti-arrhythmic agents, controlled clinical trials do not confirm that oral amiodarone increases survival.18 D0L5WM DB01119 Diazoxide small molecule approved 364-98-7 230.671 C8H7ClN2O2S Q14654#ATP-sensitive inward rectifier potassium channel 11@P00915#Carbonic anhydrase 1@P00918#Carbonic anhydrase 2@P05023#Sodium/potassium-transporting ATPase subunit alpha-1@Q12791#Calcium-activated potassium channel subunit alpha-1 Diazoxide is a potassium channel activator. Its mechanism of action revolves around enhancing cell membrane permeability to potassium ions. This action consequently elicits the relaxation of local smooth muscles. This switches off voltage-gated calcium ion channels which inhibits the generation of an action potential. D07WEP DB01120 Gliclazide small molecule approved 21187-98-4 323.411 C15H21N3O3S Q09428#ATP-binding cassette sub-family C member 8@P15692#Vascular endothelial growth factor A Based on the pharmacological properties, gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates β cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall, it potentiates insulin release and improves insulin dynamics. D0M2MR DB00114 Pyridoxal phosphate small molecule approved 54-47-7 247.1419 C8H10NO6P Q9BYV1#Alanine--glyoxylate aminotransferase 2, mitochondrial@Q99259#Glutamate decarboxylase 1@P35520#Cystathionine beta-synthase@Q16719#Kynureninase@P34896#Serine hydroxymethyltransferase, cytosolic@Q9Y697#Cysteine desulfurase, mitochondrial@P17174#Aspartate aminotransferase, cytoplasmic@P04181#Ornithine aminotransferase, mitochondrial@P11926#Ornithine decarboxylase@Q8N5Z0#Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial The two major forms of vitamin B6 are pyridoxine and pyridoxamine. In the liver they are converted to pyridoxal phosphate (PLP) which is a cofactor in many reactions of amino acid metabolism. PLP also is necessary for the enzymatic reaction governing the release of glucose from glycogen. Pyroluria is one potential cause of vitamin B6 deficiency. DB00115 Cyanocobalamin small molecule approved 68-19-9 1355.3652 C63H88CoN14O14P Q99707#Methionine synthase@P22033#Methylmalonyl-CoA mutase, mitochondrial@Q9UBK8#Methionine synthase reductase@Q8IVH4#Methylmalonic aciduria type A protein, mitochondrial@Q9Y4U1#Methylmalonic aciduria and homocystinuria type C protein@Q9RA47#Methylenetetrahydrofolate reductase General effects D0FR6I DB00118 Ademetionine small molecule approved 29908-03-0 398.44 C15H22N6O5S P21964#Catechol O-methyltransferase@Q9HBK9#Arsenite methyltransferase@Q14749#Glycine N-methyltransferase@P17707#S-adenosylmethionine decarboxylase proenzyme@P31153#S-adenosylmethionine synthase isoform type-2@P35520#Cystathionine beta-synthase@Q00266#S-adenosylmethionine synthase isoform type-1 S-adenosylmethionine is an intermediate metabolite of methionine. Its involvement in methylation assists in cellular growth and repair, maintains the phospho-bilipid layer in cell membranes. It also helps in the maintenance of the action of several hormones and neurotransmitters that affect mood. Highest concentration are found in the brain and the liver. D0U3YU DB00119 Pyruvic acid small molecule approved 127-17-3 88.0621 C3H4O3 P30613#Pyruvate kinase PKLR@P14618#Pyruvate kinase PKM@P11177#Pyruvate dehydrogenase E1 component subunit beta, mitochondrial@P11498#Pyruvate carboxylase, mitochondrial Pyruvic acid or pyruvate is a key intermediate in the glycolytic and pyruvate dehydrogenase pathways, which are involved in biological energy production. Pyruvate is widely found in living organisms. It is not an essential nutrient since it can be synthesized in the cells of the body. Certain fruits and vegetables are rich in pyruvate. For example, an average-size red apple contains approximately 450 milligrams. Dark beer and red wine are also rich sources of pyruvate. Recent research suggests that pyruvate in high concentrations may have a role in cardiovascular therapy, as an inotropic agent. Supplements of this dietary substance may also have bariatric and ergogenic applications. D0G4JI DB00120 Phenylalanine small molecule approved 63-91-2 165.1891 C9H11NO2 P17735#Tyrosine aminotransferase@Q9UHI5#Large neutral amino acids transporter small subunit 2@Q9Y285#Phenylalanine--tRNA ligase alpha subunit@P00439#Phenylalanine-4-hydroxylase@O95363#Phenylalanine--tRNA ligase, mitochondrial@Q9NSD9#Phenylalanine--tRNA ligase beta subunit@P07101#Tyrosine 3-monooxygenase Used by the brain to produce Norepinephrine, a chemical that transmits signals between nerve cells and the brain; keeps you awake and alert; reduces hunger pains; functions as an antidepressant and helps improve memory. DB00121 Biotin small molecule approved 58-85-5 244.311 C10H16N2O3S P05166#Propionyl-CoA carboxylase beta chain, mitochondrial@P50747#Biotin--protein ligase@Q9HCC0#Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial@O00763#Acetyl-CoA carboxylase 2@Q96RQ3#Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial@P11498#Pyruvate carboxylase, mitochondrial@P05165#Propionyl-CoA carboxylase alpha chain, mitochondrial@Q13085#Acetyl-CoA carboxylase 1 Biotin is a water-soluble B-complex vitamin which is composed of an ureido ring fused with a tetrahydrothiophene ring, which attaches a valeric acid substituent at one of its carbon atoms. Biotin is used in cell growth, the production of fatty acids, metabolism of fats, and amino acids. It plays a role in the Kreb cycle, which is the process in which energy is released from food. Biotin not only assists in various metabolic chemical conversions, but also helps with the transfer of carbon dioxide. Biotin is also helpful in maintaining a steady blood sugar level. Biotin is often recommended for strengthening hair and nails. Consequenty, it is found in many cosmetic and health products for the hair and skin. Biotin deficiency is a rare nutritional disorder caused by a deficiency of biotin. Initial symptoms of biotin deficiency include: Dry skin, Seborrheic dermatitis, Fungal infections, rashes including erythematous periorofacial macular rash, fine and brittle hair, and hair loss or total alopecia. If left untreated, neurological symptoms can develop, including mild depression, which may progress to profound lassitude and, eventually, to somnolence; changes in mental status, generalized muscular pains (myalgias), hyperesthesias and paresthesias. The treatment for biotin deficiency is to simply start taking some biotin supplements. A lack of biotin in infants will lead to a condition called seborrheic dermatitis or "cradle cap". Biotin deficiencies are extremely rare in adults but if it does occur, it will lead to anemia, depression, hair loss, high blood sugar levels, muscle pain, nausea, loss of appetite and inflamed mucous membranes. DB00122 Choline small molecule approved 62-49-7 104.1708 C5H14NO P36544#Neuronal acetylcholine receptor subunit alpha-7@Q9Y5K3#Choline-phosphate cytidylyltransferase B@P22303#Acetylcholinesterase@P49585#Choline-phosphate cytidylyltransferase A@O14939#Phospholipase D2@P06276#Cholinesterase@Q13393#Phospholipase D1@Q8TCT1#Phosphoethanolamine/phosphocholine phosphatase This compound is needed for good nerve conduction throughout the CNS (central nervous system) as it is a precursor to acetylcholine (ACh). Choline is also needed for gallbladder regulation, liver function and lecithin (a key lipid) formation. Choline also aids in fat and cholesterol metabolism and prevents excessive fat build up in the liver. Choline has been used to mitigate the effects of Parkinsonism and tardive dyskinesia. Choline deficiencies may result in excessive build-up of fat in the liver, high blood pressure, gastric ulcers, kidney and liver dysfunction and stunted growth. DB00123 L-Lysine small molecule approved 56-87-1 146.1876 C6H14N2O2 P30825#High affinity cationic amino acid transporter 1@O43246#Cationic amino acid transporter 4@Q8WY07#Cationic amino acid transporter 3@Q15046#Lysine--tRNA ligase Insures the adequate absorption of calcium; helps form collagen ( which makes up bone cartilage & connective tissues); aids in the production of antibodies, hormones & enzymes. Recent studies have shown that Lysine may be effective against herpes by improving the balance of nutrients that reduce viral growth. A deficiency may result in tiredness, inability to concentrate, irritability, bloodshot eyes, retarded growth, hair loss, anemia & reproductive problems. DB00126 Ascorbic acid small molecule approved 50-81-7 176.1241 C6H8O6 P24300#Xylose isomerase@O00469#Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2@O14832#Phytanoyl-CoA dioxygenase, peroxisomal@O60568#Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3@O75936#Gamma-butyrobetaine dioxygenase@P09172#Dopamine beta-hydroxylase@P19021#Peptidyl-glycine alpha-amidating monooxygenase@Q32P28#Prolyl 3-hydroxylase 1@Q8IVL5#Prolyl 3-hydroxylase 2@Q8IVL6#Prolyl 3-hydroxylase 3 Ascorbic Acid (vitamin C) is a water-soluble vitamin indicated for the prevention and treatment of scurvy, as ascorbic acid deficiency results in scurvy. Collagenous structures are primarily affected, and lesions develop in bones and blood vessels. Administration of ascorbic acid completely reverses the symptoms of ascorbic acid deficiency. DB00128 Aspartic acid small molecule approved 56-84-8 133.1027 C4H7NO4 Q9UJS0#Calcium-binding mitochondrial carrier protein Aralar2@P17174#Aspartate aminotransferase, cytoplasmic@P45381#Aspartoacylase@P08243#Asparagine synthetase [glutamine-hydrolyzing]@P00966#Argininosuccinate synthase@Q03154#Aminoacylase-1@P00505#Aspartate aminotransferase, mitochondrial@P14868#Aspartate--tRNA ligase, cytoplasmic@O75746#Calcium-binding mitochondrial carrier protein Aralar1@Q12797#Aspartyl/asparaginyl beta-hydroxylase L-aspartate is considered a non-essential amino acid, meaning that, under normal physiological conditions, sufficient amounts of the amino acid are synthesized in the body to meet the body's requirements. L-aspartate is formed by the transamination of the Krebs cycle intermediate oxaloacetate. The amino acid serves as a precursor for synthesis of proteins, oligopeptides, purines, pyrimidines, nucleic acids and L-arginine. L-aspartate is a glycogenic amino acid, and it can also promote energy production via its metabolism in the Krebs cycle. These latter activities were the rationale for the claim that supplemental aspartate has an anti-fatigue effect on skeletal muscle, a claim that was never confirmed. DB00129 Ornithine small molecule approved 70-26-8 132.161 C5H12N2O2 P04181#Ornithine aminotransferase, mitochondrial@P00480#Ornithine carbamoyltransferase, mitochondrial@P05089#Arginase-1@P54368#Ornithine decarboxylase antizyme 1@P30825#High affinity cationic amino acid transporter 1@Q9BXI2#Mitochondrial ornithine transporter 2@P78540#Arginase-2, mitochondrial@Q9Y619#Mitochondrial ornithine transporter 1@P50440#Glycine amidinotransferase, mitochondrial A non-essential and nonprotein amino acid, ornithine is critical for the production of the body's proteins, enzymes and muscle tissue. Ornithine plays a central role in the urea cycle and is important for the disposal of excess nitrogen (ammonia). Ornithine is the starting point for the synthesis of many polyamines such as putrescine and spermine. Ornithine supplements are claimed to enhance the release of growth hormone and to burn excess body fat. Ornithine is necessary for proper immune function and good liver function. DB00130 L-Glutamine small molecule approved 56-85-9 146.1445 C5H10N2O3 P17812#CTP synthase 1@Q06203#Amidophosphoribosyltransferase@P9WN38#Glutamine synthetase Like other amino acids, glutamine is biochemically important as a constituent of proteins. Glutamine is also crucial in nitrogen metabolism. Ammonia (formed by nitrogen fixation) is assimilated into organic compounds by converting glutamic acid to glutamine. The enzyme which accomplishes this is called glutamine synthetase. Glutamine can then be used as a nitrogen donor in the biosynthesis of many compounds, including other amino acids, purines, and pyrimidines. DB00131 Adenosine phosphate small molecule approved 61-19-8 347.2212 C10H14N5O7P Q13131#5'-AMP-activated protein kinase catalytic subunit alpha-1@P54646#5'-AMP-activated protein kinase catalytic subunit alpha-2@Q9Y478#5'-AMP-activated protein kinase subunit beta-1@O43741#5'-AMP-activated protein kinase subunit beta-2@P54619#5'-AMP-activated protein kinase subunit gamma-1 Adenosine monophosphate, also known as 5'-adenylic acid and abbreviated AMP, is a nucleotide that is found in RNA. It is an ester of phosphoric acid with the nucleoside adenosine. AMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase adenine. AMP is used as a dietary supplement to boost immune activity, and is also used as a substitute sweetener to aid in the maintenance of a low-calorie diet. DB00132 alpha-Linolenic acid small molecule approved 463-40-1 278.4296 C18H30O2 Q07869#Peroxisome proliferator-activated receptor alpha@P37231#Peroxisome proliferator-activated receptor gamma@P19793#Retinoic acid receptor RXR-alpha@Q03181#Peroxisome proliferator-activated receptor delta@Q96RI1#Bile acid receptor Alpha Linolenic Acid (ALA) is an 18-carbon polyunsaturated fatty acid with three double bonds. It is also called an omega-3 fatty acid, and is essential for all mammals. Alpha-linolenic acid (or omega 3 fatty acid) intake can decrease the risk of cardiovascular diseases by 1) preventing arrhythmias that can lead to sudden cardiac death, 2) decreasing the risk of thrombosis (blood clot formation) that can lead to heart attack or stroke, 3) decreasing serum triglyceride levels, 4) slowing the growth of atherosclerotic plaque, 5) improving vascular endothelial function, 6) lowering blood pressure slightly, and 7) decreasing inflammation. ALA deficiencies can lead to visual problems and sensory neuropathy. Scaly and hemorrhagic skin or scalp inflammations may also develop. DB00134 Methionine small molecule approved 63-68-3 149.211 C5H11NO2S Q9UBK8#Methionine synthase reductase@Q99707#Methionine synthase@P50579#Methionine aminopeptidase 2@Q93088#Betaine--homocysteine S-methyltransferase 1@Q9H2M3#S-methylmethionine--homocysteine S-methyltransferase BHMT2 L-Methionine is a principle supplier of sulfur which prevents disorders of the hair, skin and nails; helps lower cholesterol levels by increasing the liver's production of lecithin; reduces liver fat and protects the kidneys; a natural chelating agent for heavy metals; regulates the formation of ammonia and creates ammonia-free urine which reduces bladder irritation; influences hair follicles and promotes hair growth. L-methionine may protect against the toxic effects of hepatotoxins, such as acetaminophen. Methionine may have antioxidant activity. DB00135 Tyrosine small molecule approved 60-18-4 181.1885 C9H11NO3 P07101#Tyrosine 3-monooxygenase@Q9Y2Z4#Tyrosine--tRNA ligase, mitochondrial@P54577#Tyrosine--tRNA ligase, cytoplasmic@P17735#Tyrosine aminotransferase Tyrosine is a nonessential amino acid synthesized in the body from phenylalanine. Tyrosine is critical for the production of the body's proteins, enzymes and muscle tissue. Tyrosine is a precursor to the neurotransmitters norepinephrine and dopamine. It can act as a mood elevator and an anti-depressant. It may improve memory and increase mental alertness. Tyrosine aids in the production of melanin and plays a critical role in the production of thyroxin (thyroid hormones). Tyrosine deficiencies are manifested by hypothyroidism, low blood pressure and low body temperature. Supplemental tyrosine has been used to reduce stress and combat narcolepsy and chronic fatigue. DB00136 Calcitriol small molecule approved 32222-06-3 416.6365 C27H44O3 P11473#Vitamin D3 receptor@P31260#Homeobox protein Hox-A10 Calcitriol is a biologically active calcitrophic hormone with anti-osteoporotic, immunomodulatory, anticarcinogenic, antipsoriatic, antioxidant, and mood-modulatory activities. Its main sites of action are the intestine, bone, kidney and parathyroid hormone Label. Calcitriol is a ligand for the vitamin D nuclear receptor, which is expressed in, but not limited to, gastrointestinal (GI) tissues, bones, and kidneys 1. As an active form of vitamin D3, calcitriol elevates the plasma levels of calcium by stimulating intestinal calcium uptake, increasing reabsorption of calcium by the kidneys, and possibly increasing the release of calcium from skeletal stores. The duration of pharmacologic activity of a single dose of exogenous calcitriol is expected to be about 3 to 5 days Label. D0T2PL DB00137 Lutein small molecule approved 127-40-2 568.886 C40H56O2 Lutein was found to be present in a concentrated area of the macula, a small area of the retina responsible for central vision. The hypothesis for the natural concentration is that lutein helps protect from oxidative stress and high-energy light. Several studies show that an increase in macula pigmentation decreases the risk for eye diseases such as Age-related Macular Degeneration (AMD). DB00138 Cystine small molecule approved 56-89-3 240.3 C6H12N2O4S2 Q9UPY5#Cystine/glutamate transporter@O60931#Cystinosin L-Cystine is a covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. Cystine is a chemical substance which naturally occurs as a deposit in the urine, and can form a calculus (hard mineral formation) when deposited in the kidney. The compound produced when two cysteine molecules linked by a disulfide (S-S) bond. Cystine is required for proper vitamin B6 utilization and is also helpful in the healing of burns and wounds, breaking down mucus deposits in illnesses such as bronchitis as well as cystic fibrosis. Cysteine also assists in the supply of insulin to the pancreas, which is needed for the assimilation of sugars and starches. It increases the level of glutathione in the lungs, liver, kidneys and bone marrow, and this may have an anti-aging effect on the body by reducing age-spots etc. DB00139 Succinic acid small molecule approved 110-15-6 118.088 C4H6O4 P51649#Succinate-semialdehyde dehydrogenase, mitochondrial@Q9BXA5#Succinate receptor 1 Not Available D06VNK DB00140 Riboflavin small molecule approved 83-88-5 376.3639 C17H20N4O6 Q969G6#Riboflavin kinase@P30043#Flavin reductase (NADPH)@P0AFU8#Riboflavin synthase Riboflavin or vitamin B2 is an easily absorbed, water-soluble micronutrient with a key role in maintaining human health. Like the other B vitamins, it supports energy production by aiding in the metabolising of fats, carbohydrates, and proteins. Vitamin B2 is also required for red blood cell formation and respiration, antibody production, and for regulating human growth and reproduction. It is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin also helps in the prevention or treatment of many types of eye disorders, including some cases of cataracts. D04QST DB00141 N-Acetylglucosamine small molecule approved 7512-17-6 221.2078 C8H15NO6 P15291#Beta-1,4-galactosyltransferase 1@O60513#Beta-1,4-galactosyltransferase 4@Q9UJ70#N-acetyl-D-glucosamine kinase@Q9UK23#N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase@P54802#Alpha-N-acetylglucosaminidase@P51606#N-acylglucosamine 2-epimerase Not Available DB00142 Glutamic acid small molecule approved 56-86-0 147.1293 C5H9NO4 Q13255#Metabotropic glutamate receptor 1@Q14833#Metabotropic glutamate receptor 4@Q16099#Glutamate receptor ionotropic, kainate 4@Q16478#Glutamate receptor ionotropic, kainate 5@Q14831#Metabotropic glutamate receptor 7@O00222#Metabotropic glutamate receptor 8@O00341#Excitatory amino acid transporter 5@O14841#5-oxoprolinase@O15067#Phosphoribosylformylglycinamidine synthase@O15382#Branched-chain-amino-acid aminotransferase, mitochondrial In addition to being one of the building blocks in protein synthesis, it is the most widespread neurotransmitter in brain function, as an excitatory neurotransmitter and as a precursor for the synthesis of GABA in GABAergic neurons. DB00143 Glutathione small molecule approved 70-18-8 307.323 C10H17N3O6S P15121#Aldose reductase@P14780#Matrix metalloproteinase-9@P08684#Cytochrome P450 3A4@Q6NSD4#Glutathione peroxidase@P00390#Glutathione reductase, mitochondrial@P48637#Glutathione synthetase@P09488#Glutathione S-transferase Mu 1@Q9Y2Q3#Glutathione S-transferase kappa 1@Q16772#Glutathione S-transferase A3@P21266#Glutathione S-transferase Mu 3 Not Available D02HFD DB00144 Phosphatidyl serine small molecule approved 1446756-47-3 385.3041 C13H24NO10P P17252#Protein kinase C alpha type@P49619#Diacylglycerol kinase gamma@Q16760#Diacylglycerol kinase delta Phosphatidylserine is indicated in the treatment of cognitive impairment, including Alzheimer's disease, age-associated memory impairment and some non-Alzheimer's dementias. Further research is required before phosphatidylserine can be indicated for immune enhancement or for reduction of exercise stress. Phosphatidylserine was first isolated from brain lipids called cephalins. The major cephalins are phosphatidylserine and phophatidylethanolamine. Phosphatidylserine is involved in signal transduction activity as well as being a basic structural component of biologic membranes. DB00145 Glycine small molecule approved 56-40-6 75.0666 C2H5NO2 O75600#2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial@P13196#5-aminolevulinate synthase, nonspecific, mitochondrial@P22557#5-aminolevulinate synthase, erythroid-specific, mitochondrial@P41250#Glycine--tRNA ligase@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q14032#Bile acid-CoA:amino acid N-acyltransferase@Q14330#N-arachidonyl glycine receptor@P48637#Glutathione synthetase@Q14957#Glutamate receptor ionotropic, NMDA 2C@Q53ET4#Serine hydroxymethyltransferase Helps trigger the release of oxygen to the energy requiring cell-making process; Important in the manufacturing of hormones responsible for a strong immune system. D0M8AB DB00146 Calcifediol small molecule approved 19356-17-3 400.6371 C27H44O2 P11473#Vitamin D3 receptor Calcidiol is the precursor of vitamin D3. Vitamin D3 is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, in mineralization of bone, and for the assimilation of vitamin A. The classical manifestations of vitamin D deficiency is rickets, which is seen in children and results in bony deformaties including bowed long bones. Deficiency in adults leads to the disease osteomalacia. Both rickets and osteomalacia reflect impaired mineralization of newly synthesized bone matrix, and usually result from a combination of inadequate exposure to sunlight and decreased dietary intake of vitamin D. Common causes of vitamin D deficiency include genetic defects in the vitamin D receptor, severe liver or kidney disease, and insufficient exposure to sunlight. Vitamin D plays an important role in maintaining calcium balance and in the regulation of parathyroid hormone (PTH). It promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma. DB00148 Creatine small molecule approved 57-00-1 131.1332 C4H9N3O2 P06732#Creatine kinase M-type@P12532#Creatine kinase U-type, mitochondrial@P12277#Creatine kinase B-type@P17540#Creatine kinase S-type, mitochondrial@P48029#Sodium- and chloride-dependent creatine transporter 1@Q14353#Guanidinoacetate N-methyltransferase Creatine is a essential, non-proteinaceous amino acid derivative found in all animals. It is synthesized in the kidney, liver, and pancreas from L-arginine, glycine and L-methionine. Following its biosynthesis, creatine is transported to the skeletal muscle, heart, brain and other tissues. Most of the creatine is metabolized in these tissues to phosphocreatine (creatine phosphate). Phosphocreatine is a major energy storage form in the body. Supplemental creatine may have an energy-generating action during anaerobic exercise and may also have neuroprotective and cardioprotective actions. DB00150 Tryptophan small molecule approved 73-22-3 204.2252 C11H12N2O2 P23381#Tryptophan--tRNA ligase, cytoplasmic@P00953#Tryptophan--tRNA ligase@Q9UGM6#Tryptophan--tRNA ligase, mitochondrial Tryptophan is critical for the production of the body's proteins, enzymes and muscle tissue. It is also essential for the production of niacin, the synthesis of the neurotransmitter serotonin and melatonin. Tryptophan supplements can be used as natural relaxants to help relieve insomnia. Tryptophan can also reduce anxiety and depression and has been shown to reduce the intensity of migraine headaches. Other promising indications include the relief of chronic pain, reduction of impulsivity or mania and the treatment of obsessive or compulsive disorders. Tryptophan also appears to help the immune system and can reduce the risk of cardiac spasms. Tryptophan deficiencies may lead to coronary artery spasms. Tryptophan is used as an essential nutrient in infant formulas and intravenous feeding. Tryptophan is marketed as a prescription drug (Tryptan) for those who do not seem to respond well to conventional antidepressants. It may also be used to treat those afflicted with seasonal affective disorder (a winter-onset depression). Tryptopan serves as the precursor for the synthesis of serotonin (5-hydroxytryptamine, 5-HT) and melatonin (N-acetyl-5-methoxytryptamine). DB00151 Cysteine small molecule approved 52-90-4 121.158 C3H7NO2S Q9Y600#Cysteine sulfinic acid decarboxylase@P48637#Glutathione synthetase@P35520#Cystathionine beta-synthase@P17174#Aspartate aminotransferase, cytoplasmic@Q16878#Cysteine dioxygenase type 1@P32929#Cystathionine gamma-lyase@P16455#Methylated-DNA--protein-cysteine methyltransferase Due to this ability to undergo redox reactions, cysteine has antioxidant properties. Cysteine is an important source of sulfur in human metabolism, and although it is classified as a non-essential amino acid, cysteine may be essential for infants, the elderly, and individuals with certain metabolic disease or who suffer from malabsorption syndromes. Cysteine may at some point be recognized as an essential or conditionally essential amino acid. DB00152 Thiamine small molecule approved 70-16-6 265.355 C12H17N4OS Q9H3S4#Thiamin pyrophosphokinase 1 Thiamine is a vitamin with antioxidant, erythropoietic, cognition-and mood-modulatory, antiatherosclerotic, putative ergogenic, and detoxification activities. Thiamine has been found to protect against lead-induced lipid peroxidation in rat liver and kidney. Thiamine deficiency results in selective neuronal death in animal models. The neuronal death is associated with increased free radical production, suggesting that oxidative stress may play an important early role in brain damage associated with thiamine deficiency. Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation. Inhibition of endothelial cell proliferation may also promote atherosclerosis. Endothelial cells in culture have been found to have a decreased proliferative rate and delayed migration in response to hyperglycemic conditions. Thiamine has been shown to inhibit this effect of glucose on endothelial cells. DB00153 Ergocalciferol small molecule approved 50-14-6 396.6484 C28H44O P11473#Vitamin D3 receptor@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@Q00975#Voltage-dependent N-type calcium channel subunit alpha-1B@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A@Q15878#Voltage-dependent R-type calcium channel subunit alpha-1E After the activation of the vitamin D receptor, some of the biological changes produced by ergocalciferol include mobilization and accretion of calcium and phosphorus in the bone, absorption of calcium and phosphorus in the intestine, and reabsorption of calcium and phosphorus in the kidney.7 D06JPB DB00155 Citrulline small molecule approved 372-75-8 175.1857 C6H13N3O3 P29474#Nitric oxide synthase, endothelial@P00966#Argininosuccinate synthase@Q5T6L4#Argininosuccinate synthetase, isoform CRA_a@P00480#Ornithine carbamoyltransferase, mitochondrial@P29475#Nitric oxide synthase, brain@P35228#Nitric oxide synthase, inducible@Q9UM07#Protein-arginine deiminase type-4 A non-essential amino acid and a precursor of arginine. Citrulline supplements have been claimed to promote energy levels, stimulate the immune system and help detoxify ammonia (a cell toxin). L-citrulline is made from L-ornithine and carbamoyl phosphate in one of the central reactions in the urea cycle. It is also produced from L-arginine as a by-product of the reaction catalyzed by the enzyme NO synthase. L-citrulline, while being an amino acid, is not involved in protein synthesis and is not one of the amino acids coded for by DNA. Although citrulline cannot be incorporated in proteins during protein synthesis, several proteins are known to contain citrulline as an amino acid. These citrulline residues are generated by a family of enzymes called peptidylarginine deiminases (PADs), which convert the amino acid arginine into citrulline. Proteins that contain citrulline residues include myelin basic protein (MBP), fillagrin and several histone proteins. DB00156 Threonine small molecule approved 72-19-5 119.1192 C4H9NO3 P26639#Threonine--tRNA ligase, cytoplasmic@Q9BW92#Threonine--tRNA ligase, mitochondrial L-Threonine is an essential amino acid that helps to maintain the proper protein balance in the body. It is important for the formation of collagen, elastin, and tooth enamel, and aids liver and lipotropic function when combined with aspartic acid and methionine. DB00157 NADH small molecule approved 58-68-4 665.441 C21H29N7O14P2 O60701#UDP-glucose 6-dehydrogenase@P07327#Alcohol dehydrogenase 1A@Q00796#Sorbitol dehydrogenase@P08319#Alcohol dehydrogenase 4@P00326#Alcohol dehydrogenase 1C@P00325#Alcohol dehydrogenase 1B@P40394#Alcohol dehydrogenase class 4 mu/sigma chain@Q6ZMR3#L-lactate dehydrogenase A-like 6A@P11766#Alcohol dehydrogenase class-3@P15121#Aldose reductase A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). The action of supplemental NADH is unclear. Oral NADH supplementation has been used to combat simple fatigue as well as such mysterious and energy-sapping disorders as chronic fatigue syndrome and fibromyalgia. Researchers are also studying the value of NADH supplements for improving mental function in people with Alzheimer's disease, and minimizing physical disability and relieving depression in people with Parkinson's disease. Some healthy individuals also take NADH supplements orally to improve concentration and memory capacity, as well as to increase athletic endurance. However, to date there have been no published studies to indicate that using NADH is in any way effective or safe for these purposes. D0B8SV DB00158 Folic acid small molecule approved 59-30-3 441.3975 C19H19N7O6 P41439#Folate receptor gamma@P14207#Folate receptor beta@P15328#Folate receptor alpha Folic acid is a water-soluble B-complex vitamin found in foods such as liver, kidney, yeast, and leafy, green vegetables. Also known as folate or Vitamin B9, folic acid is an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is the precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. In order to function properly within the body, folic acid must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted by anti-metabolite therapies such as Methotrexate as they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF. DB00159 Icosapent small molecule approved 10417-94-4 302.451 C20H30O2 Q07869#Peroxisome proliferator-activated receptor alpha@P37231#Peroxisome proliferator-activated receptor gamma@P35354#Prostaglandin G/H synthase 2@O14842#Free fatty acid receptor 1@Q03181#Peroxisome proliferator-activated receptor delta@O15540#Fatty acid-binding protein, brain Eicosanoids are chemical messengers derived from 20-carbon polyunsaturated fatty acids that play critical roles in immune and inflammatory responses. Both 20-carbon omega-6 fatty acids (arachidonic acid) and 20-carbon omega-3 fatty acids (EPA) can be found in cell membranes. During an inflammatory response, arachidonic acid and EPA are metabolized by enzymes known as cyclooxygenases and lipoxygenases to form eicosanoids. Increasing omega-3 fatty acid intake increases the EPA content of cell membranes and decreases the arachidonic acid content, resulting in higher proportions of eicosanoids derived from EPA. Physiologic responses to arachidonic acid-derived eicosanoids differ from responses to EPA-derived eicosanoids. In general, eicosanoids derived from EPA are less potent inducers of inflammation, blood vessel constriction, and clotting than eicosanoids derived from arachidonic acid. D0G2MW DB00161 Valine small molecule approved 72-18-4 117.1463 C5H11NO2 P05166#Propionyl-CoA carboxylase beta chain, mitochondrial@P54687#Branched-chain-amino-acid aminotransferase, cytosolic@P26640#Valine--tRNA ligase L-valine is a branched-chain essential amino acid (BCAA) that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. Valine is one of three branched-chain amino acids (the others are leucine and isoleucine) that enhance energy, increase endurance, and aid in muscle tissue recovery and repair. This group also lowers elevated blood sugar levels and increases growth hormone production. Supplemental valine should always be combined with isoleucine and leucine at a respective milligram ratio of 2:1:2. It is an essential amino acid found in proteins; important for optimal growth in infants and for growth in children and nitrogen balance in adults. The lack of L-valine may influence the growth of body, cause neuropathic obstacle, anaemia. It has wide applications in the field of pharmaceutical and food industry. DB00162 Vitamin A small molecule approved 68-26-8 286.4516 C20H30O Q9BTZ2#Dehydrogenase/reductase SDR family member 4@P00352#Retinal dehydrogenase 1@P05090#Apolipoprotein D@P41222#Prostaglandin-H2 D-isomerase Vitamin A is effective for the treatment of Vitamin A deficiency. Vitamin A refers to a group of fat-soluble substances that are structurally related to and possess the biological activity of the parent substance of the group called all-trans retinol or retinol. Vitamin A plays vital roles in vision, epithelial differentiation, growth, reproduction, pattern formation during embryogenesis, bone development, hematopoiesis and brain development. It is also important for the maintenance of the proper functioning of the immune system. D0S7WX DB00163 Vitamin E small molecule approved 59-02-9 430.7061 C29H50O2 Q9UDX3#SEC14-like protein 4@P09917#Arachidonate 5-lipoxygenase@O76054#SEC14-like protein 2@Q9UDX4#SEC14-like protein 3@P05771#Protein kinase C beta type@O75469#Nuclear receptor subfamily 1 group I member 2@P17252#Protein kinase C alpha type@P23743#Diacylglycerol kinase alpha@P67775#Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform D02TQO DB00165 Pyridoxine small molecule approved 65-23-6 169.1778 C8H11NO3 O00764#Pyridoxal kinase Vitamin B6 (pyridoxine) is a water-soluble vitamin used in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). Vitamin B6 has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension. Hypertension is another risk factor for atherosclerosis and coronary heart disease. Another study showed pyridoxine hydrochloride to inhibit ADP- or epinephrine-induced platelet aggregation and to lower total cholesterol levels and increase HDL-cholesterol levels, again in a small group of subjects. Vitamin B6, in the form of pyridoxal 5'-phosphate, was found to protect vascular endothelial cells in culture from injury by activated platelets. Endothelial injury and dysfunction are critical initiating events in the pathogenesis of atherosclerosis. Human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities. DB00166 Lipoic acid small molecule approved 1200-22-2 206.326 C8H14O2S2 Q9Y234#Lipoyltransferase 1, mitochondrial@Q9Y289#Sodium-dependent multivitamin transporter@O43766#Lipoyl synthase, mitochondrial Lipoic acid (or α-lipoic acid) is able to pass the blood-brain barrier and is putatively used for detoxification of mercury attached to the brain cells. It can mobilise bound mercury into the blood stream as it is a mercaptan (sulfur compound which readily binds to the mercury). In the blood stream, another chelator such as dimercaptosuccinic acid (DMSA) or methylsulfonylmethane (MSM) is used to transfer mercury safely into the urine for excretion. Neither DMSA nor MSM can cross the blood-brain barrier, which is why both lipoic acid and DMSA are used. It is hypothesized that this treatment-along with carnitine, dimethylglycine (DMG), Vitamin B6, folic acid, and magnesium—could be used to treat autism and amalgam poisoning. In this hypothesis, the reason why autism is difficult to treat is that mercury is attached to the brain cells and most medicines and vitamin supplements do not penetrate the blood-brain barrier. However, α-lipoic acid and perhaps vitamin B12 could making it possible for other chelators to remove mercury safely out of the body and could perhaps one day be used as a treatment for autism. Because lipoic acid is related to cellular uptake of glucose and it is both soluble in water and fat, it is being used for treatment in diabetes. It may be helpful for people with Alzheimer's disease or Parkinson's disease. DB00169 Cholecalciferol small molecule approved 67-97-0 384.6377 C27H44O P11473#Vitamin D3 receptor The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 cholecalciferol (or D2) occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D 12,13,14. These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization 12,13,14. Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules 12,13,14. There exists a period of 10 to 24 hours between the administration of cholecalciferol and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys 12,13,14. It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys 12,13,14. D0K5WS DB00170 Menadione small molecule approved 58-27-5 172.18 C11H8O2 P38435#Vitamin K-dependent gamma-carboxylase@Q9BQB6#Vitamin K epoxide reductase complex subunit 1@Q8N0U8#Vitamin K epoxide reductase complex subunit 1-like protein 1@P00734#Prothrombin@P00740#Coagulation factor IX@P04070#Vitamin K-dependent protein C@P07225#Vitamin K-dependent protein S@P16083#Ribosyldihydronicotinamide dehydrogenase [quinone]@P02818#Osteocalcin Menadione (Vitamin K3) is a fat-soluble vitamin precursor that is converted into menaquinone in the liver. Vitamin K1 and K2 are the naturally occurring types of vitamin K. The former, which is also known as phylloquinone, is synthesized by plants and can be found in such foods as spinach, broccoli, lettuce, and soybeans. The latter, sometimes alternatively referred to as menaquinone, is primarily produced by bacteria in the anterior part of the gut and the intestines. Vitamin K3, on the other hand, is one of the many manmade versions of vitamin K. Also called menadione, this yellowish, synthetic crystalline substance is converted into the active form of the K2 vitamin inside of the animal body. While a vitamin K deficiency can be dangerous, especially to infants that may easily suffer from extensive hemorrhaging, an overdose can be as equally detrimental. Newborns that are administered too great a dosage of vitamin K3 can suffer from kernicterus, a form of severe brain damage that may produce decreased movement, loss of appetite, seizures, deafness, mental retardation, and even death. This condition is associated with an abnormally high concentration of bilirubin, a bile pigment, in the tissues of the brain, which can be caused by the presence of K3. For this reason, K3 is less often utilized medically than it was in former times. D03GET DB00173 Adenine small molecule approved 73-24-5 135.1267 C5H5N5 P07741#Adenine phosphoribosyltransferase@Q13126#S-methyl-5'-thioadenosine phosphorylase@O00763#Acetyl-CoA carboxylase 2@P24666#Low molecular weight phosphotyrosine protein phosphatase@Q9BY49#Peroxisomal trans-2-enoyl-CoA reductase@P78362#SRSF protein kinase 2 Adenine (sometimes known as vitamin B4) combines with the sugar ribose to form adenosine, which in turn can be bonded with from one to three phosphoric acid units, yielding AMP, ADP and ATP . These adenine derivatives perform important functions in cellular metabolism. Adenine is one of four nitrogenous bases utilized in the synthesis of nucleic acids. A modified form of adenosine monophosphate (cyclic AMP) is an imporant secondary messenger in the propagation of many hormonal stimuli. Adenine is an integral part of the structure of many coenzymes. Adenosine (adenine with a ribose group) causes transient heart block in the AV node of the heart. In individuals suspected of suffering from a supraventricular tachycardia (SVT), adenosine is used to help identify the rhythm. Certain SVTs can be successfully terminated with adenosine. D08IBS DB00174 Asparagine small molecule approved 70-47-3 132.1179 C4H8N2O3 P08243#Asparagine synthetase [glutamine-hydrolyzing]@O43776#Asparagine--tRNA ligase, cytoplasmic@Q7L266#Isoaspartyl peptidase/L-asparaginase@Q96I59#Probable asparagine--tRNA ligase, mitochondrial A non-essential amino acid. Asparagine is critical for the production of the body's proteins, enzymes and muscle tissue. Supplements of this amino acid are claimed to balance nervous system function. DB00175 Pravastatin small molecule approved 81093-37-0 424.5277 C23H36O7 P04035#3-hydroxy-3-methylglutaryl-coenzyme A reductase@Q92769#Histone deacetylase 2 The action of pravastatin on the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase produces an increase in the expression of hepatic LDL receptors which in order decreases the plasma levels of LDL cholesterol.10 D02RQU DB00176 Fluvoxamine small molecule approved 54739-18-3 318.34 C15H21F3N2O2 P31645#Sodium-dependent serotonin transporter@Q12809#Potassium voltage-gated channel subfamily H member 2 Fluvoxamine, an aralkylketone-derivative agent Label, is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other SSRIs 1. It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety 1. The antidepressant, antiobsessive-compulsive, and antibulimic actions of Fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin Label,1,2. In vitro studies show that Fluvoxamine is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake 2. Moreover, apart from binding to σ1 receptors 2, fluvoxamine has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs 1. Furthermore, some studies have demonstrated that the chronic administration of Fluvoxamine was found to downregulate brain norepinephrine receptors (as has been observed with other drugs effective in the treatment of major depressive disorder), while others suggest the opposite 3. D03HFG DB00177 Valsartan small molecule approved 137862-53-4 435.5188 C24H29N5O3 P30556#Type-1 angiotensin II receptor Valsartan inhibits the pressor effects of angiotensin II with oral doses of 80 mg inhibiting the pressor effect by about 80% at peak with approximately 30% inhibition persisting for 24 hours. Removal of the negative feedback of angiotensin II causes a 2- to 3-fold rise in plasma renin and consequent rise in angiotensin II plasma concentration in hypertensive patients. Minimal decreases in plasma aldosterone were observed after administration of valsartan. D06UDG DB00178 Ramipril small molecule approved 87333-19-5 416.5106 C23H32N2O5 P12821#Angiotensin-converting enzyme@P46663#B1 bradykinin receptor Ramipril is an ACE inhibitor similar to benazepril, fosinopril and quinapril. 5 It is an inactive prodrug that is converted to ramiprilat in the liver, the main site of activation, and kidneys. Ramiprilat confers blood pressure lowing effects by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of ramiprilat by causing increased vasodilation and decreased blood pressure. D01STB DB00179 Masoprocol small molecule approved 27686-84-6 302.3649 C18H22O4 P09917#Arachidonate 5-lipoxygenase@P04278#Sex hormone-binding globulin Masoprocol is a novel antineoplastic agent. It is not known exactly how masoprocol works. Laboratory experiments have shown that masoprocol prevents cells similar to the ones found in actinic keratoses from multiplying. Masoprocol was withdrawn from the U.S. market in June 1996. D0U3YB DB00180 Flunisolide small molecule approved 3385-03-3 434.4977 C24H31FO6 P04150#Glucocorticoid receptor Flunisolide is a synthetic corticosteroid. It is administered either as an oral metered-dose inhaler for the treatment of asthma or as a nasal spray for treating allergic rhinitis. Corticosteroids are naturally occurring hormones that prevent or suppress inflammation and immune responses. When given as an intranasal spray, flunisolide reduces watery nasal discharge (rhinorrhea), nasal congestion, postnasal drip, sneezing, and itching oat the back of the throat that are common allergic symptoms. D0FM2P DB00181 Baclofen small molecule approved 1134-47-0 213.661 C10H12ClNO2 O75899#Gamma-aminobutyric acid type B receptor subunit 2@P61073#C-X-C chemokine receptor type 4@Q9UBS5#Gamma-aminobutyric acid type B receptor subunit 1 Baclofen is an antispasmodic agent that induces muscle relaxation. It reduces the release of excitatory neurotransmitters in the pre-synaptic neurons and stimulates inhibitory neuronal signals in the post-synaptic neurons.6 Oral formulations of baclofen are the most commonly used form of the drug. In one cross-section study, intrathecal baclofen was more effective than oral baclofen in relieving spasticity directly at the level of the spinal cord.8 Baclofen has CNS depression properties and can cause sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression.13 Baclofen also mediates some antinociceptive effects and stimulates gastric acid secretion.15 D01AJY DB00182 Amphetamine small molecule approved 300-62-9 135.2062 C9H13N P14416#D(2) dopamine receptor@Q16568#Cocaine- and amphetamine-regulated transcript protein@P27338#Amine oxidase [flavin-containing] B@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P21397#Amine oxidase [flavin-containing] A@P27338#Amine oxidase [flavin-containing] B From its mechanism of action, it has been demonstrated that amphetamine augments the concentration of noradrenaline in the prefrontal cortex and dopamine in the striatum on a dose and time-dependent manner. The indistinct release of neurotransmitters which include adrenaline is known to produce cardiovascular side effects.5 D05BMG DB00183 Pentagastrin small molecule approved 5534-95-2 767.9 C37H49N7O9S P32239#Gastrin/cholecystokinin type B receptor Pentagastrin is indicated as a diagnostic aid for evaluation of gastric acid secretory function. It is effective in testing for anacidity (achlorhydria) in patients with suspected pernicious anemia, atrophic gastritis, or gastric carcinoma. It is also effective in determining the reduction in acid output after operations for peptic ulcer, such as vagotomy or gastric resection. D0O5TQ DB00184 Nicotine small molecule approved 54-11-5 162.2316 C10H14N2 P28329#Choline O-acetyltransferase@P43681#Neuronal acetylcholine receptor subunit alpha-4@P17787#Neuronal acetylcholine receptor subunit beta-2@P11511#Aromatase@P36544#Neuronal acetylcholine receptor subunit alpha-7@Q9UGM1#Neuronal acetylcholine receptor subunit alpha-9@P30926#Neuronal acetylcholine receptor subunit beta-4@P32297#Neuronal acetylcholine receptor subunit alpha-3 Nicotine, the primary alkaloid in tobacco products binds stereo-selectively to nicotinic-cholinergic receptors on autonomic ganglia, the adrenal medulla, neuromuscular junctions and in the brain. Nicotine exerts two effects, a stimulant effect exerted at the locus ceruleus and a reward effect in the limbic system. Itranvenous administration of nicotine causes release of acetylcholine, norepinephrine, dopamine, serotonine, vasopressin, beta-endorphin and ACTH. Nicotine is a highly addictive substance. Nicotine also induces peripheral vasoconstriction, tachycardia and elevated blood pressure. Nicotine inhalers and patches are used to treat smoking withdrawl syndrome. Nicotine is classified as a stimulant of autonomic ganglia. D0T8GD DB00185 Cevimeline small molecule approved 107233-08-9 199.313 C10H17NOS P20309#Muscarinic acetylcholine receptor M3 D0Q4CS DB00186 Lorazepam small molecule approved 846-49-1 321.158 C15H10Cl2N2O2 P28472#Gamma-aminobutyric acid receptor subunit beta-3 The effect of lorazepam in GABA-A receptors produces an increase in the frequency of opening of the chloride ion channel. However, for its effect to generate, the neurotransmitter is required.8 The anticonvulsant properties of lorazepam are thought to be related to the binding to voltage-dependent sodium channels in which the sustained repetitive firing gets limited by the slow recovery of sodium channels due to the benzodiazepine effect.9 D0E0OG DB00187 Esmolol small molecule approved 81147-92-4 295.374 C16H25NO4 P08588#Beta-1 adrenergic receptor Not Available D03XTC DB00188 Bortezomib small molecule approved 179324-69-7 384.237 C19H25BN4O4 P28074#Proteasome subunit beta type-5@P20618#Proteasome subunit beta type-1 Bortezomib works to target the ubiquitin-proteasome pathway, an essential molecular pathway that regulates intracellular concentrations of proteins and promotes protein degradation.1 The ubiquitin-proteasome pathway is often dysregulated in pathological conditions, leading to aberrant pathway signalling and the formation of malignant cells. In one study, patient-derived chronic lymphocytic leukemia (CLL) cells contained 3-fold higher levels of chymotrypsin-like proteasome activity than normal lymphocytes.1 By reversibly inhibiting proteasome, bortezomib prevents proteasome-mediated proteolysis. Bortezomib exerts a cytotoxic effect on various cancer cell types in vitro and delays tumour growth in vivo in nonclinical tumour models.7 Bortezomib inhibits the proteasome activity in a dose-dependent manner. In one pharmacodynamic study, more than 75% of proteasome inhibition was observed in whole blood samples within one hour after dosing of bortezomib.4 D0SH3I DB00189 Ethchlorvynol small molecule approved 113-18-8 144.6 C7H9ClO P28472#Gamma-aminobutyric acid receptor subunit beta-3 Ethchlorvynol is a sedative drug and schedule IV (USA) controlled substance. It produces cerebral depression, however the exact mechanism of action is not known. D03VZH DB00190 Carbidopa small molecule approved 28860-95-9 226.2292 C10H14N2O4 P20711#Aromatic-L-amino-acid decarboxylase When mixed with levodopa, carbidopa inhibits the peripheral conversion of levodopa to dopamine and the decarboxylation of oxitriptan to serotonin by aromatic L-amino acid decarboxylase. This results in an increased amount of levodopa and oxitriptan available for transport to the central nervous system. Carbidopa also inhibits the metabolism of levodopa in the GI tract, thus, increasing the bioavailability of levodopa.4 D0P7JZ DB00191 Phentermine small molecule approved 122-09-8 149.2328 C10H15N P23975#Sodium-dependent noradrenaline transporter@P31645#Sodium-dependent serotonin transporter@Q01959#Sodium-dependent dopamine transporter@P21397#Amine oxidase [flavin-containing] A@P27338#Amine oxidase [flavin-containing] B@P01303#Pro-neuropeptide Y It is reported that the main mechanism of action of phentermine is the generation of appetite suppression, maybe due to the increase in leptin, but it is considered that other mechanisms should be involved.4 Some reports have indicated that the weight loss effect is mainly due to the increase in resting energy expenditure.3 D0U0RZ DB00192 Indecainide small molecule approved 74517-78-5 308.4174 C20H24N2O Q14524#Sodium channel protein type 5 subunit alpha Indecainide is a rarely used antidysrhythmic. Indecainide has local anesthetic activity and belongs to the membrane stabilizing (Class 1) group of antiarrhythmic agents; it has electrophysiologic effects characteristic of the IC class of antiarrhythmics. D0K4CQ DB00193 Tramadol small molecule approved 27203-92-5 263.3752 C16H25NO2 P20309#Muscarinic acetylcholine receptor M3@P25103#Substance-P receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor@Q99250#Sodium channel protein type 2 subunit alpha@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B Tramadol modulates the descending pain pathways within the central nervous system through the binding of parent and M1 metabolite to μ-opioid receptors and the weak inhibition of the reuptake of norepinephrine and serotonin.7,6 D05GKD DB00194 Vidarabine small molecule approved 24356-66-9 267.2413 C10H13N5O4 P09252#DNA polymerase catalytic subunit@P13159#Thymidine kinase@P13159#Thymidine kinase Vidarabine is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV). The inhibitory activity of Vidarabine is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts Vidarabine into Vidarabine monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, Vidarabine triphosphate stops the DNA replication of herpes virus by being incorporated into the DNA strand and preventing the formation of phosphodiester bridges between bases. This ultimately leads to destabilization of the viral DNA strands. D0NI0C DB00195 Betaxolol small molecule approved 63659-18-7 307.4278 C18H29NO3 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor Betaxolol is a competitive, beta(1)-selective (cardioselective) adrenergic antagonist. Betaxolol is used to treat hypertension, arrhythmias, coronary heart disease, glaucoma, and is also used to reduce non-fatal cardiac events in patients with heart failure. Activation of beta(1)-receptors (located mainly in the heart) by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Drugs such as betaxolol that block these receptors therefore have the reverse effect: they lower the heart rate and blood pressure and hence are used in conditions when the heart itself is deprived of oxygen. They are routinely prescribed in patients with ischemic heart disease. In addition, beta(1)-selective blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels. Betaxolol is lipophilic and exhibits no intrinsic sympathomimetic activity (ISA) or membrane stabilizing activity. D03ROX DB00196 Fluconazole small molecule approved 86386-73-4 306.2708 C13H12F2N6O Fluconazole has been demonstrated to show fungistatic activity against the majority of strains of the following microorganisms, curing fungal infections27: D09LNI DB00197 Troglitazone small molecule approved 97322-87-7 441.54 C24H27NO5S P37231#Peroxisome proliferator-activated receptor gamma@P62508#Estrogen-related receptor gamma@P11474#Steroid hormone receptor ERR1@Q03181#Peroxisome proliferator-activated receptor delta@Q07869#Peroxisome proliferator-activated receptor alpha@P09211#Glutathione S-transferase P@O60488#Long-chain-fatty-acid--CoA ligase 4@P05121#Plasminogen activator inhibitor 1@Q99808#Equilibrative nucleoside transporter 1 Troglitazone is an oral antihyperglycemic agent which acts primarily by decreasing insulin resistance. Troglitazone is used in the management of type II diabetes (noninsulin-dependent diabetes mellitus (NIDDM) also known as adult-onset diabetes). It improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Troglitazone is not chemically or functionally related to either the sulfonylureas, the biguanides, or the g-glucosidase inhibitors. Troglitazone may be used concomitantly with a sulfonylurea or insulin to improve glycemic control. D06XZW DB00198 Oseltamivir small molecule approved 196618-13-0 312.4045 C16H28N2O4 Q9Y3R4#Sialidase-2 D0O5NK DB00199 Erythromycin small molecule approved 114-07-8 733.9268 C37H67NO13 O43193#Motilin receptor@Q12809#Potassium voltage-gated channel subfamily H member 2 Macrolides, such as erythromycin, stop bacterial growth by inhibiting protein synthesis and translation, treating bacterial infections.8 Erythromycin does not exert effects on nucleic acid synthesis.21 This drug has been shown to be active against most strains of the following microorganisms, effectively treating both in vitro and clinical infections. Despite this, it is important to perform bacterial susceptibility testing before administering this antibiotic, as resistance is a common issue that may affect treatment.21 D02YIZ DB00200 Hydroxocobalamin small molecule approved 13422-51-0 1346.3551 C62H89CoN13O15P Q99707#Methionine synthase@P22033#Methylmalonyl-CoA mutase, mitochondrial@Q8IVH4#Methylmalonic aciduria type A protein, mitochondrial@P20061#Transcobalamin-1@Q9BXJ7#Protein amnionless@O60494#Cubilin@Q9Y4U1#Methylmalonic aciduria and homocystinuria type C protein Hydroxocobalamin is a synthetic, injectable form of Vitamin B12. Hydroxocobalamin is actually a precursor of two cofactors or vitamins (Vitamin B12 and Methylcobalamin) which are involved in various biological systems in man. Vitamin B12 is required for the conversion of methylmalonate to succinate. Deficiency of this enzyme could therefore interfere with the production of lipoprotein in myelin sheath tissue and so give rise to neurological lesions. The second cofactor, Methylcobalamin, is necessary for the conversion of homocysteine to methionine which is essential for the metabolism of folic acid. Deficiency of tetrahydrafolate leads to reduced synthesis of thymidylate resulting in reduced synthesis of DNA which is essential for cell maturation. Vitamin B12 is also concerned in the maintenance of sulphydryl groups in reduced form, deficiency leading to decreased amounts of reduced SH content of erythrocytes and liver cells. Overall, vitamin B12 acts as a coenzyme for various metabolic functions, including fat and carbohydrate metabolism and protein synthesis. It is necessary for growth, cell replication, hematopoiesis, and nucleoprotein as well as myelin synthesis. This is largely due to its effects on metabolism of methionine folic acid, and malonic acid. D0VF4H DB00201 Caffeine small molecule approved 58-08-2 194.1906 C8H10N4O2 P0DMS8#Adenosine receptor A3@P29274#Adenosine receptor A2a@Q01064#Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B@Q08499#cAMP-specific 3',5'-cyclic phosphodiesterase 4D@Q13370#cGMP-inhibited 3',5'-cyclic phosphodiesterase B@O76074#cGMP-specific 3',5'-cyclic phosphodiesterase Caffeine stimulates the central nervous system (CNS), heightening alertness, and sometimes causing restlessness and agitation. It relaxes smooth muscle, stimulates the contraction of cardiac muscle, and enhances athletic performance.1,12,18 Caffeine promotes gastric acid secretion and increases gastrointestinal motility. It is often combined in products with analgesics and ergot alkaloids, relieving the symptoms of migraine and other types of headaches. Finally, caffeine acts as a mild diuretic.12 D0B3HD DB00202 Succinylcholine small molecule approved 306-40-1 290.399 C14H30N2O4 P20309#Muscarinic acetylcholine receptor M3@P08172#Muscarinic acetylcholine receptor M2@P32297#Neuronal acetylcholine receptor subunit alpha-3@P43681#Neuronal acetylcholine receptor subunit alpha-4@P36544#Neuronal acetylcholine receptor subunit alpha-7@Q9UGM1#Neuronal acetylcholine receptor subunit alpha-9@P17787#Neuronal acetylcholine receptor subunit beta-2@P30926#Neuronal acetylcholine receptor subunit beta-4 Succinylcholine's neuromuscular blockade takes effect within 60 seconds of intravenous administration and lasts between four to six minutes.2 Similar to acetylcholine, it binds to cholinergic receptors of the motor endplate to induce membrane depolarization and, eventually, muscle paralysis, which may be maintained for as long as an adequate concentration of succinylcholine remains at the receptor site.8 Succinylcholine has no direct action on smooth or cardiac muscle, nor does it appear to act on pre-synaptic or ganglionic acetylcholine receptors.5 The paralysis induced by succinylcholine has been described as "progressive", first involving the muscles of the face and glottis, then the intercostals and diaphragm, then followed by other skeletal muscles.8 D0Q7ZQ DB00203 Sildenafil small molecule approved 139755-83-2 474.576 C22H30N6O4S O76074#cGMP-specific 3',5'-cyclic phosphodiesterase@P18545#Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma@Q13956#Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma@P11926#Ornithine decarboxylase@Q9NZQ7#Programmed cell death 1 ligand 1 In vitro studies have shown that sildenafil is selective for phosphodiesterase-5 (PDE5) 11,12,13,14,15,16,8,9. Its effect is more potent on PDE5 than on other known phosphodiesterases 11,12,13,14,15,16,8,9. In particular, there is a 10-times selectivity over PDE6 which is involved in the phototransduction pathway in the retina 11,12,13,14,15,16,8,9. There is an 80-times selectivity over PDE1, and over 700-times over PDE 2, 3, 4, 7, 8, 9, 10 and 11 11,12,13,14,15,16,8,9. And finally, sildenafil has greater than 4,000-times selectivity for PDE5 over PDE3, the cAMP-specific phosphodiesterase isoform involved in the control of cardiac contractility 11,12,13,14,15,16,8,9. DB00204 Dofetilide small molecule approved 115256-11-6 441.565 C19H27N3O5S2 Q12809#Potassium voltage-gated channel subfamily H member 2@O95069#Potassium channel subfamily K member 2@Q14500#ATP-sensitive inward rectifier potassium channel 12 Dofetilide is an antiarrhythmic drug with Class III (cardiac action potential duration prolonging) properties and is indicated for the maintenance of normal sinus rhythm. Dofetilide increases the monophasic action potential duration in a predictable, concentration-dependent manner, primarily due to delayed repolarization. At concentrations covering several orders of magnitude, Dofetilide blocks only IKr with no relevant block of the other repolarizing potassium currents (e.g., IKs, IK1). At clinically relevant concentrations, Dofetilide has no effect on sodium channels (associated with Class I effect), adrenergic alpha-receptors, or adrenergic beta-receptors. D0NW3X DB00205 Pyrimethamine small molecule approved 58-14-0 248.711 C12H13ClN4 P00374#Dihydrofolate reductase@P13922#Bifunctional dihydrofolate reductase-thymidylate synthase@P07686#Beta-hexosaminidase subunit beta Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides. D0C0SK DB00206 Reserpine small molecule approved 50-55-5 608.6787 C33H40N2O9 Q05940#Synaptic vesicular amine transporter@P54219#Chromaffin granule amine transporter@O15392#Baculoviral IAP repeat-containing protein 5 Reserpine is an adrenergic blocking agent used to treat mild to moderate hypertension via the disruption of norepinephrine vesicular storage. The antihypertensive actions of Reserpine are a result of its ability to deplete catecholamines from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral resistance. D0J4JM DB00207 Azithromycin small molecule approved 83905-01-5 748.9845 C38H72N2O12 Q9UM07#Protein-arginine deiminase type-4 Macrolides stop bacterial growth by inhibiting protein synthesis and translation, treating bacterial infections 4. DB00208 Ticlopidine small molecule approved 55142-85-3 263.786 C14H14ClNS Q9H244#P2Y purinoceptor 12 Ticlopidine is a prodrug that is metabolised to an as yet undetermined metabolite that acts as a platelet aggregation inhibitor. Inhibition of platelet aggregation causes a prolongation of bleeding time. In its prodrug form, ticlopidine has no significant in vitro activity at the concentrations attained in vivo. D05LBU DB00209 Trospium small molecule approved 47608-32-2 392.518 C25H30NO3 P20309#Muscarinic acetylcholine receptor M3@P11229#Muscarinic acetylcholine receptor M1 Trospium is an antispasmodic, antimuscarinic agent indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. According to receptor assays, it displays higher affinity towards muscarininc receptors compared to nicotinic receptors at therapeutic concentrations. D05TIB DB00210 Adapalene small molecule approved 106685-40-9 412.5201 C28H28O3 P28702#Retinoic acid receptor RXR-beta@P13631#Retinoic acid receptor gamma@P10826#Retinoic acid receptor beta@P19793#Retinoic acid receptor RXR-alpha@P17174#Aspartate aminotransferase, cytoplasmic@P10276#Retinoic acid receptor alpha@P48443#Retinoic acid receptor RXR-gamma@P05412#Transcription factor AP-1@O60603#Toll-like receptor 2 D0JC9N DB12107 Vaborbactam small molecule approved 1360457-46-0 297.13 C12H16BNO5S P05364#Beta-lactamase@Q939N4#Beta-lactamase@Q9L5C7#Beta-lactamase@Q840M4#Beta-lactamase@P62593#Beta-lactamase TEM@P0AD64#Beta-lactamase SHV-1@Q9F663#Carbapenem-hydrolyzing beta-lactamase KPC Vaborbactam shows no antibacterial activity alone; it serves to restore the antibacterial activity of other antibacterial agents such as meropenem by attenuating their degradation by inhibiting certain serine beta-lactamases of microorganisms.Label Vaborbactam does not decrease the activity of meropenem against meropenem-susceptible organisms.Label Vaborbactam in combination with meropenem, which is a penem antibacterial drug, potentiates the bactericidal actions of meropenem against carbapenem-resistant KPC-containing Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae in a concentration-dependent manner.3 It restored the antimicrobial activity of meropenem in animal models of infection caused by some meropenem non-susceptible KPC-producing Enterobacteriaceae.Label DR6BU1 DB12127 Sultamicillin small molecule approved 76497-13-7 594.65 C25H30N4O9S2 Not Available DB12130 Lorlatinib small molecule approved 1454846-35-5 406.421 C21H19FN6O2 Q9UM73#ALK tyrosine kinase receptor Based on data from Study B7461001, exposure-response relationships for Grade 3 or 4 hypercholesterolemia and for any Grade 3 or 4 adverse reaction were observed at steady-state exposures achieved at the recommended dosage, with higher probability of the occurrence of adverse reactions with increasing lorlatinib exposure Label. D0AF6O DB12141 Gilteritinib small molecule approved 1254053-43-4 552.724 C29H44N8O3 P36888#Receptor-type tyrosine-protein kinase FLT3@Q9UM73#ALK tyrosine kinase receptor@P28222#5-hydroxytryptamine receptor 1B@P41595#5-hydroxytryptamine receptor 2B@P30530#Tyrosine-protein kinase receptor UFO In preclinical trials, gilteritinib demonstrate an IC50 for the wild-type receptor of 5 nM, 0.7-1.8 nM for ITD-mutated and comparable inhibition to other therapies in the TKD-mutated. As well, data showed a gilteritinib-driven inhibition of the receptor tyrosine kinase AXL which is known to modulate the activity of FLT3 in acute myeloid leukemia.5 Another important result in vivo was the localization in high levels in xenografted tumors which indicated high selectivity.6 D04KZY DB12147 Erdafitinib small molecule approved 1346242-81-6 446.555 C25H30N6O2 P11362#Fibroblast growth factor receptor 1@P21802#Fibroblast growth factor receptor 2@P22607#Fibroblast growth factor receptor 3@P22455#Fibroblast growth factor receptor 4@O43519#RET proto-oncogene@P07333#Macrophage colony-stimulating factor 1 receptor@P16234#Platelet-derived growth factor receptor alpha@P09619#Platelet-derived growth factor receptor beta@P10721#Mast/stem cell growth factor receptor Kit@P35968#Vascular endothelial growth factor receptor 2 Upon administration, it was observed that erdafitinib increased serum phosphate level as a consequence of FGFR inhibition Label1,3. Erdafitinib should be increased to the maximum recommended dose to achieve target serum phosphate levels of 5.5– 7.0 mg/dL in early cycles with continuous daily dosing Label1,3. D0NW0T DB12153 Citicoline small molecule approved 987-78-0 488.324 C14H26N4O11P2 A0A0H2UQB5#LicC protein Not Available D02CFP DB12161 Deutetrabenazine small molecule approved 1392826-25-3 323.466 C19H27NO3 Q05940#Synaptic vesicular amine transporter In clinical trials, there was an evidence of clinical effectiveness of deutetrabenazine in improving the symptoms of involuntary movements in patient with tardive dyskinesia by reducing the mean Abnormal Involuntary Movement Scale (AIMS) score 3,4. In a randomized, double-blind, placebo-controlled crossover study in healthy male and female subjects, single dose administration of 24 mg deutetrabenazine results in an approximately 4.5 msec mean increase in QTc Label. Effects at higher exposures to deutetrabenazine or its metabolites have not been evaluated Label. Deutetrabenazine and its metabolites were shown to bind to melanin-containing tissues including eyes, skin and fur in pigmented rats. After a single oral dose of radiolabeled deutetrabenazine, radioactivity was still detected in eye and fur at 35 days following dosing Label. D0E7ZU DB12243 Edaravone small molecule approved 89-25-8 174.203 C10H10N2O Edaravone scavenges free hydroxyl radicals and peroxynitrite radicals which are highly associated with neuronal damage/death from many cerebral vascular disorders such as ischemic strokes and degenerative neurological disorders such as ALS. It exerts a neuroprotective and antioxidant effect and delays disease progression by limiting the extent of lipid peroxidation via free radical generation and cell membrane damage from oxidative stress. It reversed the reduction in regional blood flow and cerebral edema in a case of ischemic stroke. DB12245 Triclabendazole small molecule approved 68786-66-3 359.65 C14H9Cl3N2OS Q24940#Cathepsin L-like proteinase Triclabendazole and its metabolites are active against both the immature and mature worms of Fasciola hepatica and DB12267 Brigatinib small molecule approved 1197953-54-0 584.1 C29H39ClN7O2P Q9UM73#ALK tyrosine kinase receptor@P00533#Epidermal growth factor receptor@P00519#Tyrosine-protein kinase ABL1@P08069#Insulin-like growth factor 1 receptor@P36888#Receptor-type tyrosine-protein kinase FLT3@P06213#Insulin receptor@P08581#Hepatocyte growth factor receptor@Q15303#Receptor tyrosine-protein kinase erbB-4@P04626#Receptor tyrosine-protein kinase erbB-2 Brigitanib inhibits proliferation and in vitro viability of cells expressing the fusion protein EML4-ALK as well as 17 crizotinib-resistant ALK mutants. Its action is expanded to cells expressing EGFR deletions, ROS1-L2026M, FLT3-F691L and FLT3-D835Y.5 Brigitanib presents a dose-dependent inhibition of tumor growth, tumor burden and prolonged survival in mice EML4-ALK xenograft models.6 Time course of Brigatinib and exposure-response studies are still unknown. D08PIE DB12278 Propiverine small molecule approved 60569-19-9 367.4813 C23H29NO3 P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08912#Muscarinic acetylcholine receptor M5@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@P35348#Alpha-1A adrenergic receptor@P08173#Muscarinic acetylcholine receptor M4 Propiverine hydrochloride inhibits abnormal contractions of bladder smooth muscle in vivo through not only its anticholinergic activity but also its concurrent calcium antagonistic activity 8. Through the above-mentioned mechanism, propiverine is able to relieve the symptoms of overactive bladder. D0TV9K DB12293 Nefopam small molecule approved 13669-70-0 253.345 C17H19NO Not Available D05AFX DB12300 P-nitrobiphenyl small molecule approved 92-93-3 199.209 C12H9NO2 Not Available DB12301 Doravirine small molecule approved 1338225-97-0 425.749 C17H11ClF3N5O3 Q72547#Reverse transcriptase/RNaseH In a clinical phase 2 trial evaluating a dose range of 0.25-2x the recommended dose of doravirine (in combination with emtricitabine/tenofovir) in HIV-1 infected subjects with no antiretroviral treatment history, no exposure-response relationship for efficacy was identified for doravirine.5 DB12313 Dopexamine small molecule approved 86197-47-9 356.5017 C22H32N2O2 Not Available D0V7XF DB12328 Cantharidin small molecule approved 56-25-7 196.202 C10H12O4 P35869#Aryl hydrocarbon receptor Cantharidin is a natural toxin produced by the blistering beetle that possesses both vesicant (blistering) and keratolytic effects 1,2. The substance elicits these effects by inducing acantholysis (loss of intercellular connections) through the targeting of the desmosomal dense plaque, resulting in the detachment of the desmosomes from the tonofilaments 1,2. Cantharidin's effectiveness against warts is proposed to be a result of the exfoliation of the wart body as a consequence of the compound's acantholytic action 8. This acantholytic action generally does not go beyond the epidermal cells so that the basal layer remains intact and minimal effect occurs on the corium 8. There is consequently no scarring from the topical application of cantharidin 8. D0Z2RA DB12329 Eravacycline small molecule approved 1207283-85-9 558.563 C27H31FN4O8 P0A7V8#30S ribosomal protein S4 Eravacycline is an antibiotic that disrupts bacterial protein synthesis, treating complicated intraabdominal infections Label. DB12332 Rucaparib small molecule approved 283173-50-2 323.371 C19H18FN3O P09874#Poly [ADP-ribose] polymerase 1@Q9UGN5#Poly [ADP-ribose] polymerase 2@Q9Y6F1#Poly [ADP-ribose] polymerase 3 Rucaparib is an anticancer agent that exerts cytotoxic effects against cancer cells. It works by inhibiting poly (ADP-ribose) polymerase (PARP), an enzyme that plays a role in DNA repair. Rucaparib inhibits PARP-1, PARP-2, and PARP-3. It also interacts with PARP-4, PARP-10, PARP-12, PARP-15, and PARP-16, but to a lesser extent.1 In mice, rucaparib accumulated and was retained in tumours, inhibiting PARP enzymes for seven days.4 D01SHZ DB12343 Temocillin small molecule approved 66148-78-5 414.45 C16H18N2O7S2 Not Available DB12362 Diaminopropanol tetraacetic acid small molecule approved 3148-72-9 322.27 C11H18N2O9 Not Available DB12364 Betrixaban small molecule approved 330942-05-7 451.91 C23H22ClN5O3 P00742#Coagulation factor X Betrixaban is an oral anticoagulant that excerts its action by preventing thrombin generation without having a direct effect on platelet aggregation 5. DB12371 Siponimod small molecule approved 1230487-00-9 516.605 C29H35F3N2O3 Q9H228#Sphingosine 1-phosphate receptor 5@P21453#Sphingosine 1-phosphate receptor 1 Immune system effects D07FKQ DB12377 Relebactam small molecule approved 1174018-99-5 348.37 C12H20N4O6S P05364#Beta-lactamase@Q939N4#Beta-lactamase@Q9L5C7#Beta-lactamase@Q840M4#Beta-lactamase@P62593#Beta-lactamase TEM DB12401 Bromperidol small molecule approved 10457-90-6 420.322 C21H23BrFNO2 Not Available D00SHQ DB12407 Iobitridol small molecule approved 136949-58-1 835.169 C20H28I3N3O9 Not Available D07ZBE DB12434 Steviolbioside small molecule approved 41093-60-1 642.739 C32H50O13 Not Available DB12455 Omadacycline small molecule approved 389139-89-3 556.66 C29H40N4O7 P0AG59#30S ribosomal protein S14@P0A7U3#30S ribosomal protein S19@P0A7V3#30S ribosomal protein S3@P0A7W7#30S ribosomal protein S8@P02359#30S ribosomal protein S7 Omadacycline can be either bacteriostatic or bacteriocidal depending on the organism involved.1,3 It disrupts bacterial protein synthesis without affecting DNA, RNA, or peptidoglycan synthesis. Omadacycline represents an improvement over existing tetracycline agents as it has not been found to be subject to tetracycline resistance mediated by tetracycline efflux pumps encoded by the tet(K), tet(L), and tet(B) or to ribosomal protection proteins encoded by tet(O) and tet(M).Label,1,2 Omadacycline is susceptible to RNA mutations which confer resistance to tetracyclines.4 D09GUJ DB12457 Rimegepant small molecule approved 1289023-67-1 534.568 C28H28F2N6O3 Q16602#Calcitonin gene-related peptide type 1 receptor Rimegepant helps to abort migraine headaches by preventing the activity of a pronociceptive molecule that has been implicated in migraine pathophysiology.6 It is intended for use as an abortive migraine therapy and therefore has a relatively rapid onset of effect, with most efficacy trials evaluating for effect at the 2 hour mark.6 D0V9VG DB12466 Favipiravir small molecule approved 259793-96-9 157.104 C5H4FN3O2 Favipiravir functions as a prodrug and undergoes ribosylation and phosphorylation intracellularly to become the active favipiravir-RTP.7,10 Favipiravir-RTP binds to and inhibits RNA dependent RNA polymerase (RdRp), which ultimately prevents viral transcription and replication.7,8 D0Y4LX DB12473 Taurolidine small molecule approved 19388-87-5 284.35 C7H16N4O4S2 Not Available DB12474 Lynestrenol small molecule approved 52-76-6 284.443 C20H28O Not Available DB12483 Copanlisib small molecule approved 1032568-63-0 480.529 C23H28N8O4 P42336#Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform@O00329#Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Copanlisib has demonstrated potent anti-tumor and pro-apoptotic activity in various tumor cell lines and xenograft models 1. In clinical trials, 59 percent of patients receiving copanlisib achieved complete or partial shrinkage of their tumors after a median of 12.2 months 2. Higher systemic levels of copanlisib is associated with elevated plasma glucose levels. DB12492 Piritramide small molecule approved 302-41-0 430.5851 C27H34N4O Not Available D0RX3C DB12500 Fedratinib small molecule approved 936091-26-8 524.678 C27H36N6O3S O60674#Tyrosine-protein kinase JAK2@P36888#Receptor-type tyrosine-protein kinase FLT3@P23458#Tyrosine-protein kinase JAK1 Fedratinib is a kinase inhibitor that inhibits cell division and induces apoptosis.7 Patients taking fedratinib may experience anemia, thrombocytopenia, gastrointestinal toxicity, hepatic toxicity, or elevated amylase and lipase.7 These effects should be managed by reducing the dose, temporarily stopping the medication, or providing transfusions on a case by case basis.7 D0G8BM DB12523 Mizolastine small molecule approved 108612-45-9 432.503 C24H25FN6O Not Available D06MAJ DB12529 Nitrite small molecule approved 14797-65-0 46.0055 NO2 Not Available DB12532 Oxetacaine small molecule approved 126-27-2 467.654 C28H41N3O3 P01350#Gastrin Oxetacaine improves common gastrointestinal symptoms.3 Oxetacaine is part of the anesthetic antacids which increase the gastric pH while providing relief from pain for a longer period of duration at a lower dosage. This property has been reported to relieve the symptoms of hyperacidity. Oxetacaine is reported to produce a reversible loss of sensation and to provide a prompt and prolonged relief of pain. In vitro, oxetacaine was showed to produce an antispasmodic action on the smooth muscle and block the action of serotonin.4 DB12537 Benzodiazepine small molecule approved 12794-10-4 144.177 C9H8N2 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Not Available D0CS6N DB12554 Mebeverine small molecule approved 3625-06-7 429.557 C25H35NO5 Not Available D0VU8Q DB12602 Pentetreotide small molecule approved 138661-02-6 1394.58 C63H87N13O19S2 Not Available DB12612 Ozanimod small molecule approved 1306760-87-1 404.47 C23H24N4O3 P21453#Sphingosine 1-phosphate receptor 1@Q9H228#Sphingosine 1-phosphate receptor 5 Ozanimod reduces circulating lymphocytes that cause the neuroinflammation associated with MS, reducing debilitating symptoms and, possibly, disease progression. During clinical trials, ozanimod reduced MS-associated brain volume loss in several regions.1,11 Ozanimod causes the sequestration of peripheral lymphocytes, reducing circulating lymphocytes in the gastrointestinal tract.7 D07EDB DB12615 Plazomicin small molecule approved 1154757-24-0 592.691 C25H48N6O10 P0AG59#30S ribosomal protein S14 Plazomicin exerts its antibacterial activity in a dose-dependent manner with a post-antibiotic effect ranging from 0.2 to 2.6 hours at 2X MIC against Enterobacteriaceae, as demonstrated by in vitro studies Label. In clinical trials comprising of hospitalized adult patients with cUTI (including pyelonephritis), resolution or improvement of clinical cUTI symptoms and a microbiological outcome of eradication were observed at day 5 following the first dose administration of plazomicin Label. Plazomicin has shown to elicit nephrotoxic, ototoxic, and neuromuscular blocking effects. In clinical trials, it did not induce any clinically relevant QTc-prolonging effects Label. D0E6BB DB12667 Protionamide small molecule approved 14222-60-7 180.27 C9H12N2S Not Available DB12674 Lurbinectedin small molecule approved 497871-47-3 784.88 C41H44N4O10S Lurbinectedin exerts its chemotherapeutic activity by covalently binding to DNA, resulting in double-strand DNA breaks and subsequent cell death.1 Lurbinectedin has been associated with myelosuppression, and patients receiving therapy with this agent should be closely monitored for evidence of cytopenias. Prior to beginning therapy, ensure baseline neutrophil counts are >1,500 cells/mm3 and platelet counts are >100,000/mm3.7 The supplementary use of granulocyte colony-stimulating factor (G-CSF) should be considered if the neutrophil count falls below 500 cells/mm3.7 Lurbinectedin has also been associated with hepatotoxicity.7 Monitor liver function tests at baseline and regular intervals throughout therapy, and consider holding, reducing, or permanently discontinuing therapy based on the severity of observed hepatotoxicity.7 D0V6OA DB12710 Perazine small molecule approved 84-97-9 339.5 C20H25N3S Not Available D07JWT DB12728 Fenpropidin small molecule approved 67306-00-7 273.464 C19H31N Not Available DB12754 Iodide small molecule approved 20461-54-5 126.9045 I Not Available DB12767 Gaxilose small molecule approved 14087-31-1 312.271 C11H20O10 Not Available DB12783 Benserazide small molecule approved 322-35-0 257.246 C10H15N3O5 P20711#Aromatic-L-amino-acid decarboxylase When used as a therapy for treating Parkinson's disease, levadopa's specific mechanism of action revolves around its metabolism into dopamine in the body 3,2. Unfortunately, the resultant increase in the levels of circulating dopamine in the blood and to various extracerebral tissues can result in a number of side effects like nausea, vomiting, or even cardiac arrhythmias that may diminish patient adherence 3,2. A decarboxylase inhibitor like benserazide is consequently an effective compound to combine with levadopa as it is incapable of crossing the blood-brain barrier itself and therefore allows levadopa to elicit its primary action in the central nervous system, but will prevent the formation of dopamine from levadopa in extracerebral tissues - thereby acting to minimize the occurrence of extracerebral side effects 3,2. D0X8ED DB12789 Dinoprost small molecule approved 551-11-1 354.487 C20H34O5 Q9Y5Y4#Prostaglandin D2 receptor 2 Not Available DB12792 Boscalid small molecule approved 188425-85-6 343.207 C18H12Cl2N2O Not Available D0R4EY DB12808 Trifarotene small molecule approved 895542-09-3 459.586 C29H33NO4 P13631#Retinoic acid receptor gamma@P10826#Retinoic acid receptor beta@P10276#Retinoic acid receptor alpha Trifarotene exerts its effects via agonism at retinoid receptors - these receptors function to alter DNA transcription, resulting in downstream modulation of the expression of various genes involved in acne pathogenesis.5 It may be associated with skin irritation and should not be applied to cuts, abrasions, or otherwise damaged skin. As trifarotene may result in photosensitivity, patients should be cautioned to avoid excess sun exposure and to use sunscreen and/or protective clothing if exposure is unavoidable.6 D06FOU DB12821 Perflubutane small molecule approved 355-25-9 238.028 C4F10 Not Available DB12825 Lefamulin small molecule approved 1061337-51-6 507.73 C28H45NO5S Lefamulin demonstrates strong antibacterial activity against several microbes that are found to be common in both acute bacterial skin and skin structure infections as well as community-acquired bacterial pneumonia.1,3 It shows antibacterial activity against gram-positive and atypical microbes (for example, Streptococcus pneumoniae, Legionella pneumophila, Mycoplasma pneumoniae, Haemophilus influenzae, and Chlamydophila pneumoniae). Lefamulin also exerts activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium. It does not treat Pseudomonas aeruginosa infections.11 During in vitro studies, drug has also has demonstrated activity against Neisseria gonorrhoeae and Mycoplasma genitalium.11 D0EB5N DB12834 Secnidazole small molecule approved 3366-95-8 185.183 C7H11N3O3 imidazole ring.4 Upon entering the target pathogen, the nitro group of secnidazole is reduced by bacterial or parasitic nitroreductase enzymes, producing radical anions and reactive intermediates. Radical anions and reactive intermediates cause the depletion of thiols, DNA helix damage, disruption of bacterial or parasitic protein synthesis and replication, and ultimately, cell death of susceptible isolates of Gram positive bacteria, Gram negative bacteria and T. vaginalis.4,6 D0V5IW DB12839 Pegvaliase small molecule approved 1585984-95-7 318.414 C15H30N2O5 D0T8HZ DB12865 Etelcalcetide small molecule approved 1262780-97-1 1048.26 C38H73N21O10S2 P41180#Extracellular calcium-sensing receptor Following a single intravenous bolus administration of etelcalcetide, PTH levels decreased within 30 minutes post dose. In the single-dose study, the extent and duration of the reduction in PTH increased with increasing dose. Reduction in PTH levels correlated with plasma etelcalcetide concentrations in hemodialysis patients. The reduction in PTH resulted in reductions in calcium and attenuation of post-dialytic phosphate elevation. The effect of reducing PTH levels was maintained throughout the 6-month dosing period when etelcalcetide was administered by intravenous bolus three times a week. D07RYI DB12867 Benperidol small molecule approved 2062-84-2 381.451 C22H24FN3O2 Not Available D0X7QQ DB12877 Oxatomide small molecule approved 60607-34-3 426.564 C27H30N4O Not Available D0AJ5L DB12887 Tazemetostat small molecule approved 1403254-99-8 572.75 C34H44N4O4 Q15910#Histone-lysine N-methyltransferase EZH2@Q92800#Histone-lysine N-methyltransferase EZH1 Tazemetostat is a methyltransferase inhibitor that prevents hyper-trimethylation of histones and inhibits cancer cell de-differentiation.6 The duration of action is long as it is given twice daily.6 Patients should be counselled regarding the risk of secondary malignancies and embryo-fetal toxicity.6 D00EQL DB12911 Nicoboxil small molecule approved 13912-80-6 223.272 C12H17NO3 Topical applications consisting of the individual active ingredients of nicoboxil and nonivamide at doses considered to be therapeutic are generally not considered readily available commercially 1. Subsequently, the pharmacodynamics of nicoboxil are considered useful in commercially available combination products largely because they combine with those of nonivamide to offer a synergistic effect from the unique complementary actions of these two agents 5. DB12924 Ozenoxacin small molecule approved 245765-41-7 363.417 C21H21N3O3 P0AFI2#DNA topoisomerase 4 subunit A Although the exposure response relationship for ozenoxacin after it has been applied topically has not yet been studied, a formal relationship is unlikely because systemic exposure of ozenoxacin following its topical application has been measured to be negligible 1. D0X1HE DB12938 Isoxaflutole small molecule approved 141112-29-0 359.32 C15H12F3NO4S Not Available DB12941 Darolutamide small molecule approved 1297538-32-9 398.85 C19H19ClN6O2 P10275#Androgen receptor@P06401#Progesterone receptor Darolutamide, through its downstream effects on cancer cell growth, treats castrate-resistant prostate cancer. It inhibits cancer cell growth and markedly lowers prostate specific antigen (PSA) levels through potent androgen receptor antagonism.3,4,6 D0DV6D DB12942 Lactitol small molecule approved 585-86-4 344.3124 C12H24O11 Lactitol helps to facilitate bowel movements by drawing water into the gastrointestinal tract.4 The oral administration of lactitol may reduce the absorption of concomitant medications - other oral medications should be administered at least 2 hours before or 2 hours after lactitol.4 D0C1BG DB12945 Dihydralazine small molecule approved 484-23-1 190.21 C8H10N6 Not Available D0QS1U DB12952 Methylprednisone small molecule approved 91523-05-6 372.461 C22H28O5 Not Available DB12954 Terizidone small molecule approved 25683-71-0 302.29 C14H14N4O4 Not Available DB12965 Silver small molecule approved 7440-22-4 107.8682 Ag P02768#Serum albumin@P01023#Alpha-2-macroglobulin@P00450#Ceruloplasmin@P02795#Metallothionein-2@P25713#Metallothionein-3 Silver exhibits a broad-spectrum antimicrobial activity. Silver ions were shown to mediate an effective antibacterial action against Streptococcus mutans, one of major bacteria present in the human oral cavity and one of etiological microorganism of dental caries 3. A study reported a dose-dependent antimicrobial activity of silver nanoparticles against MRSA and non-MRSA bacteria 2. Silver nanoparticles were also shown to mediate antibacterial activity against Gram-positive S. aureus and Gram-negative E. coli by inhibiting the growth 4. DB12978 Pexidartinib small molecule approved 1029044-16-3 417.82 C20H15ClF3N5 P07333#Macrophage colony-stimulating factor 1 receptor@P10721#Mast/stem cell growth factor receptor Kit@P36888#Receptor-type tyrosine-protein kinase FLT3@P09619#Platelet-derived growth factor receptor beta Pexidartinib works by suppressing the growth of tenosynovial giant cell tumors. In clinical trials comprising of patients with symptomatic tenosynovial giant cell tumor, pexidartinib had a higher overall response rate, characterized by improved patient symptoms and functional outcomes, compared to placebo.2 Pexidartinib works by inhibiting the activation and signaling of tumor-permissive cytokines and receptor tyrosine kinases that play a central role in tumor cell proliferation and survival.3 D09TAB DB12982 Silicon small molecule approved 7440-21-3 28.085 Si Not Available DB13063 Parthenolide small molecule approved 20554-84-1 248.3175 C15H20O3 Not Available D0M4KE DB13074 Macimorelin small molecule approved 381231-18-1 474.565 C26H30N6O3 Q92847#Growth hormone secretagogue receptor type 1 Maximum GH levels from stimulation are observed between 30 to 90 minutes after administration of macimorelin Label. Increase in the QTcF interval may be observed from macimorelin administration Label. D0BV3J DB13076 Yttrium Y-90 small molecule approved 10098-91-6 89.9072 Y Not Available DB13100 Biguanide small molecule approved 56-03-1 101.113 C2H7N5 Not Available DB13114 Amitriptylinoxide small molecule approved 4317-14-0 293.41 C20H23NO Not Available DB13116 Norflurane small molecule approved 811-97-2 102.032 C2H2F4 Not Available DB13117 Pentafluoropropane small molecule approved 460-73-1 134.049 C3H3F5 Not Available DB13125 Lusutrombopag small molecule approved 1110766-97-6 591.54 C29H32Cl2N2O5S P40238#Thrombopoietin receptor The AUC of lusutrombopag was found to correlate the increased platelet counts. Following administration of 3 mg daily dose in patients with chronic liver disease and thrombocytopenia, the mean (standard deviation) maximum platelet count in patients (N=74) without platelet transfusion was 86.9 (27.2) × 10^9/L, and the median time to reach the maximum platelet count was 12.0 (5 to 35) days Label. Lusutrombopag was not shown to induce any clinically significant QTc prolongation at a dose 8 times the recommended dosage Label. D0TD1R DB13136 Fluindione small molecule approved 957-56-2 240.233 C15H9FO2 DB13139 Levosalbutamol small molecule approved 34391-04-3 239.3107 C13H21NO3 P07550#Beta-2 adrenergic receptor It acts by relaxing smooth muscle in the bronchial tubes to increase air flow and relieve acute shortness of breath. DB13142 Calcium glubionate anhydrous small molecule approved 97635-31-9 592.513 C18H32CaO19 Not Available DB01121 Phenacemide small molecule approved 63-98-9 178.1879 C9H10N2O2 P35498#Sodium channel protein type 1 subunit alpha Phenacemide is a ureal anticonvulsant indicated for control of severe epilepsy, particularly mixed forms of complex partial (psychomotor or temporal lobe) seizures, refractory to other anticonvulsants. Phenacemide elevates the threshold for minimal electroshock convulsions and abolishes the tonic phase of maximal electroshock seizures. It also prevents or modifies seizures induced by pentylenetetrazol or other convulsants. D07ONP DB01122 Ambenonium small molecule approved 7648-98-8 537.565 C28H42Cl2N4O2 P22303#Acetylcholinesterase Ambenonium, similar to pyridostigmine and neostigmine, is used for the treatment of muscle weakness and fatigue in people with myasthenia gravis. It is postulated to exert its therapeutic effect by enhancing cholinergic function through the inhibition of the acetylcholine hydrolysis by acetylcholinesterase. Increased levels of acetylcholine has peripheral effects, as acetylcholine is also used in the brain, where it tends to cause excitatory actions. The glands that receive impulses from the parasympathetic part of the autonomic nervous system are also stimulated in the same way. This is why an increase in acetylcholine causes a decreased heart rate and increased production of saliva. Ambenonium is used less commonly than neostigmine or pyridostigmine but may be preferred in patients hypersensitive to the bromide ion. Ambenonium produces fewer muscarinic side effects than neostigmine, but more than pyridostigmine. D06IAQ DB01123 Proflavine small molecule approved 92-62-6 209.2465 C13H11N3 P00734#Prothrombin@P0A0N4#HTH-type transcriptional regulator QacR@Q58L87#TetR family transcriptional regulator Proflavine is an acriflavine derivative which is a disinfectant bacteriostatic against many gram-positive bacteria. Proflavine is toxic and carcinogenic in mammals and so it is used only as a surface disinfectant or for treating superficial wounds. D08GSF DB01124 Tolbutamide small molecule approved 64-77-7 270.348 C12H18N2O3S Q09428#ATP-binding cassette sub-family C member 8@P48048#ATP-sensitive inward rectifier potassium channel 1 Tolbutamide, a first-generation sulfonylurea antidiabetic agent, is used with diet to lower blood glucose levels in patients with diabetes mellitus type II. Tolbutamide is twice as potent as the related second-generation agent glipizide. Tolbutamide lowers blood sugar by stimulating the pancreas to secrete insulin and helping the body use insulin efficiently. The pancreas must be able to produce insulin for this drug to work. D06OIV DB01125 Anisindione small molecule approved 117-37-3 252.2647 C16H12O3 P38435#Vitamin K-dependent gamma-carboxylase Anisindione is a synthetic anticoagulant and an indanedione derivative. It is prescribed only if you cannot take coumarin-type anticoagulants such as coumadin as anisindione is a powerful drug with serious potential side effects. Anticoagulants decrease the clotting ability of the blood and therefore help to prevent harmful clots from forming in the blood vessels. These medicines are sometimes called blood thinners, although they do not actually thin the blood. They also will not dissolve clots that already have formed, but they may prevent the clots from becoming larger and causing more serious problems. D09WKB DB01126 Dutasteride small molecule approved 164656-23-9 528.5297 C27H30F6N2O2 P18405#3-oxo-5-alpha-steroid 4-dehydrogenase 1@P31213#3-oxo-5-alpha-steroid 4-dehydrogenase 2 Dutasteride is a synthetic 4-azasteroid compound that selectively inhibits both the type I and type II isoforms of steroid 5α-reductase, an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone (DHT). Dutasteride works by reducing the levels of circulating DHT. It was also shown to reduce the size of the prostate gland, improve urinary flow, and symptoms of benign prostatic hyperplasia alone or in combination with tamsulosin.14 The effect of the reduction of DHT by dutasteride is dose-dependent, with the maximum effect observed within 1-2 weeks following initial administration.15 D0A9YA DB01127 Econazole small molecule approved 27220-47-9 381.684 C18H15Cl3N2O O75469#Nuclear receptor subfamily 1 group I member 2 Econazole is an antifungal medication related to fluconazole (Diflucan), ketoconazole (Nizoral), itraconazole (Sporanox), and clotrimazole (Lotrimin, Mycelex). Econazole prevents fungal organisms from producing vital substances required for growth and function. This medication is effective only for infections caused by fungal organisms. It will not work for bacterial or viral infections. D0EV8E DB01128 Bicalutamide small molecule approved 90357-06-5 430.373 C18H14F4N2O4S P10275#Androgen receptor Bicalutamide is an antineoplastic hormonal agent primarily used in the treatment of prostate cancer. Bicalutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently, Bicalutamide blocks the action of androgens of adrenal and testicular origin which stimulate the growth of normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen monotherapy has not consistently been shown to be equivalent to castration. D0V9BD DB01129 Rabeprazole small molecule approved 117976-89-3 359.443 C18H21N3O3S P20648#Potassium-transporting ATPase alpha chain 1 Rabeprazole prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Rabeprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Rabeprazole may also be used with antibiotics to get rid of bacteria that are associated with some ulcers. Rabeprazole is a selective and irreversible proton pump inhibitor, suppresses gastric acid secretion by specific inhibition of the H+, K+ -ATPase, which is found at the secretory surface of parietal cells. In doing so, it inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen. D0KL4J DB01130 Prednicarbate small molecule approved 73771-04-7 488.577 C27H36O8 P04150#Glucocorticoid receptor Corticosteroids diffuse across cell membranes and complex with specific cytoplasmic receptors. These complexes then enter the cell nucleus, bind to DNA (chromatin), and stimulate transcription of messenger RNA (mRNA) and subsequent protein synthesis of various inhibitory enzymes responsible for the anti-inflammatory effects of topical corticosteroids. These anti-inflammatory effects include inhibition of early processes such as edema, fibrin deposition, capillary dilatation, movement of phagocytes into the area, and phagocytic activities. Later processes, such as capillary production, collagen deposition, and keloid formation also are inhibited by corticosteroids. D09IEE DB01131 Proguanil small molecule approved 500-92-5 253.731 C11H16ClN5 P00374#Dihydrofolate reductase@P13922#Bifunctional dihydrofolate reductase-thymidylate synthase Proguanil is a biguanide derivative that is converted to an active metabolite called cycloguanil. It exerts its antimalarial action by inhibiting parasitic dihydrofolate reductase enzyme. It has causal prophylactic and suppressive activity against P. falciparum and cures the acute infection. It is also effective in suppressing the clinical attacks of vivax malaria. However it is slower compared to 4-aminoquinolines. D0P8RS DB01132 Pioglitazone small molecule approved 111025-46-8 356.439 C19H20N2O3S P37231#Peroxisome proliferator-activated receptor gamma@P27338#Amine oxidase [flavin-containing] B Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal, and improves impaired glucose homeostasis.1 In patients with type 2 diabetes mellitus, these effects result in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c values.1 D03OFF DB01133 Tiludronic acid small molecule approved 89987-06-4 318.608 C7H9ClO6P2S Q05209#Tyrosine-protein phosphatase non-receptor type 12@P29350#Tyrosine-protein phosphatase non-receptor type 6@P23469#Receptor-type tyrosine-protein phosphatase epsilon Tiludronic acid is a bisphosphonate that prevents osteoclasts from resorbing bone.8 The duration of action is quite long due to the slow clearance from the bone, and the therapeutic window is wide.8 Patients should be counselled regarding the risk of upper GI mucosal irritation as well as gastric and duodenal ulcers.8 D0Q8CS DB01135 Doxacurium small molecule approved 106791-39-3 1035.2223 C56H78N2O16 Q15822#Neuronal acetylcholine receptor subunit alpha-2@P08172#Muscarinic acetylcholine receptor M2 Doxacurium chloride is a long-acting, nondepolarizing skeletal muscle relaxant. The neuromuscular block produced by doxacurium chloride may be antagonized by anticholinesterase agents. As with other nondepolarizing neuromuscular blocking agents, the more profound the neuromuscular block at reversal, the longer the time and the greater the dose of anticholinesterase required for recovery of neuromuscular function. Doxacurium chloride is approximately 2.5 to 3 times more potent than pancuronium and 10 to 12 times more potent than metocurine. D0Y7TO DB01136 Carvedilol small molecule approved 72956-09-3 406.4742 C24H26N2O4 P08588#Beta-1 adrenergic receptor Carvedilol reduces tachycardia through beta adrenergic antagonism and lowers blood pressure through alpha-1 adrenergic antagonism.5,6 It has a long duration of action as it is generally taken once daily and has a broad therapeutic index as patients generally take 10-80mg daily.5,6 Patients taking carvedilol should not abruptly stop taking this medication as this may exacerbate coronary artery disease.5,6 D0W9LX DB01137 Levofloxacin small molecule approved 100986-85-4 361.3675 C18H20FN3O4 Levofloxacin is bactericidal and exerts its antimicrobial effects via inhibition of bacterial DNA replication.9 It has a relatively long duration of action in comparison with other antibiotics that allows for once or twice daily dosing. Levofloxacin is associated with QTc-interval prolongation and should be used with caution in patients with other risk factors for prolongation (e.g. hypokalemia, concomitant medications).9 D02RSN DB01138 Sulfinpyrazone small molecule approved 57-96-5 404.482 C23H20N2O3S Q96S37#Solute carrier family 22 member 12@P33527#Multidrug resistance-associated protein 1@Q92887#Canalicular multispecific organic anion transporter 1@O75469#Nuclear receptor subfamily 1 group I member 2 Sulfinpyrazone's pharmacologic activity is the potentiation of the urinary excretion of uric acid. It is useful for reducing the blood urate levels in patients with chronic tophaceous gout and acute intermittent gout, and for promoting the resorption of tophi. D03DEI DB01139 Cefapirin small molecule approved 21593-23-7 423.463 C17H17N3O6S2 Cephapirin is a first-generation cephalosporin that has a wide spectrum of activity against gram-positive and gram-negative organisms. Cephapirin is more resistant to beta-lactamases than are the penicillins and so is effective against staphylococci, with the exception of methicillin-resistant staphylococci. DB01140 Cefadroxil small molecule approved 50370-12-2 363.388 C16H17N3O5S P0A3M6#Penicillin-binding protein 2B@Q8DR59#Penicillin-binding protein 1A@Q7CRA4#Penicillin-binding protein 1b Cefadroxil, a first-generation cephalosporin antibiotic, is used to treat urinary tract infections, skin and skin structure infections, pharyngitis, and tonsillitis. D0X9ZC DB01141 Micafungin small molecule approved 235114-32-6 1270.274 C56H71N9O23S Formerly known as FK463, micafungin is a semisynthetic lipopeptide synthesized from a fermentation product of Coleophoma empetri that works as an antifungal agent. It is a glucan synthesis inhibitor of the echinocandin structural class. The U.S. Food and Drug Administration approved micafungin in March 2005. Micafungin inhibits an enzyme essential for fungal cell-wall synthesis. Depending on its concentration, micafungin may be fungicidal against some Candida, but is usually fungistatic against Apergillus. Micafungin can be used concomitantly with a variety of other drugs, including the HIV protease inhibitor ritonavir and the transplant medications cyclosporine and tacrolimus. D06TOE DB01142 Doxepin small molecule approved 1668-19-5 279.3761 C19H21NO P20309#Muscarinic acetylcholine receptor M3@Q12809#Potassium voltage-gated channel subfamily H member 2@P41595#5-hydroxytryptamine receptor 2B@P35367#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2 D06FES DB01143 Amifostine small molecule approved 20537-88-6 214.223 C5H15N2O3PS D06CIE DB01144 Diclofenamide small molecule approved 120-97-8 305.159 C6H6Cl2N2O4S2 P00918#Carbonic anhydrase 2@P00915#Carbonic anhydrase 1@P22748#Carbonic anhydrase 4@P43166#Carbonic anhydrase 7@P07451#Carbonic anhydrase 3 Dichlorphenamide is an oral carbonic anhydrase inhibitor indicated for adjunctive treatment of: chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. Carbonic anhydrase inhibitors reduce intraocular pressure by partially suppressing the secretion of aqueous humor (inflow). DB01145 Sulfoxone small molecule approved 144-76-3 404.482 C14H16N2O6S3 Q27738#Dihydropteroate synthetase Sulfoxone is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus. D0PI2E DB01146 Diphenylpyraline small molecule approved 147-20-6 281.392 C19H23NO P70174#Histamine H1 receptor@Q01959#Sodium-dependent dopamine transporter Diphenylpyraline is an antihistamine that prevents, but does not reverse, responses mediated by histamine alone. Diphenylpyraline antagonizes most of the pharmacological effects of histamine, including urticaria and pruritus. Also, diphenylpyraline may exhibit anticholinergic actions (as do most of the antihistamines) and may thus provide a drying effect on the nasal mucosa. D0W6DY DB01147 Cloxacillin small molecule approved 61-72-3 435.881 C19H18ClN3O5S P59676#Penicillin-binding protein 2X@P0AEB2#D-alanyl-D-alanine carboxypeptidase DacA@Q8DR59#Penicillin-binding protein 1A Cloxacillin is a semisynthetic antibiotic in the same class as penicillin. Cloxacillin is for use against staphylococci that produce beta-lactamase. D04KTZ DB01148 Flavoxate small molecule approved 15301-69-6 391.4596 C24H25NO4 P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2 Flavoxate is a spasmolytic flavone derivative that acts by relaxing the smooth muscle in the urinary tract. Flavoxate is a competitive muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Muscarinic receptors play an important role in several major cholin-ergically mediated functions, including contractions of urinary bladder smooth muscle and stimulation of salivary secretion. D0ND2J DB01149 Nefazodone small molecule approved 83366-66-9 470.007 C25H32ClN5O2 P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P31645#Sodium-dependent serotonin transporter@P08908#5-hydroxytryptamine receptor 1A@P23975#Sodium-dependent noradrenaline transporter@Q01959#Sodium-dependent dopamine transporter@P35368#Alpha-1B adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P35348#Alpha-1A adrenergic receptor@Q12809#Potassium voltage-gated channel subfamily H member 2 Nefazodone, an antidepressant synthetically derived phenylpiperazine, is used to treat major depression. Although it is structurally similar to trazodone, nefazodone has a mechanism of action different from other antidepressants and, hence, lacks the risk for major cardiovascular toxicity seen with tricyclics and insomnia and inhibition of REM sleep seen with the selective serotonin reuptake inhibitors. D0X7DE DB01150 Cefprozil small molecule approved 92665-29-7 389.426 C18H19N3O5S P14677#Penicillin-binding protein 2x@Q04707#Penicillin-binding protein 1A Cefprozil, a semisynthetic, second-generation cephalosporin, is used to treat otitis media, soft-tissue infections, and respiratory tract infections. D0YX4S DB01151 Desipramine small molecule approved 50-47-5 266.3807 C18H22N2 P20309#Muscarinic acetylcholine receptor M3@P08588#Beta-1 adrenergic receptor@P35367#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2@P07550#Beta-2 adrenergic receptor@P14416#D(2) dopamine receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Desipramine, a secondary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. It is the active metabolite of imipramine, a tertiary amine TCA. The acute effects of desipramine include inhibition of noradrenaline re-uptake at noradrenergic nerve endings and inhibition of serotonin (5-hydroxy tryptamine, 5HT) re-uptake at the serotoninergic nerve endings in the central nervous system. Desipramine exhibits greater noradrenergic re-uptake inhibition compared to the tertiary amine TCA imipramine. In addition to inhibiting neurotransmitter re-uptake, desipramine down-regulates beta-adrenergic receptors in the cerebral cortex and sensitizes serotonergic receptors with chronic use. The overall effect is increased serotonergic transmission. Antidepressant effects are typically observed 2 - 4 weeks following the onset of therapy though some patients may require up to 8 weeks of therapy prior to symptom improvement. Patients experiencing more severe depressive episodes may respond quicker than those with mild depressive symptoms. D01UTL DB01152 Candicidin small molecule approved 1403-17-4 1109.317 C59H84N2O18 Candicidin is a polyene antifungal antibiotic produced by a strain of Streptomyces griseus. It is especially effective against Candida albicans (more effective than amphotericin B), and is administered intravaginally in the treatment of vulvovaginal candidiasis. D0I6IP DB01153 Sertaconazole small molecule approved 99592-32-2 437.77 C20H15Cl3N2OS Sertaconazole is an imidazole/triazole type antifungal agent. Sertaconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Sertaconazole exhibits in vitro activity against Cryptococcus neoformans and Candida spp. Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans. D0O6UZ DB01154 Thiamylal small molecule approved 77-27-0 254.349 C12H18N2O2S Q15842#ATP-sensitive inward rectifier potassium channel 8@Q14654#ATP-sensitive inward rectifier potassium channel 11@P14867#Gamma-aminobutyric acid receptor subunit alpha-1 Thiamylal, a barbiturate, is used in combination with acetaminophen or aspirin and caffeine for its sedative and relaxant effects in the treatment of tension headaches, migraines, and pain. Barbiturates act as nonselective depressants of the central nervous system (CNS), capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. In sufficiently high therapeutic doses, barbiturates induce anesthesia. D06NSA DB01155 Gemifloxacin small molecule approved 175463-14-6 389.3809 C18H20FN5O4 Gemifloxacin is a quinolone/fluoroquinolone antibiotic. Gemifloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Gemifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. D0VR7W DB01156 Bupropion small molecule approved 34911-55-2 239.741 C13H18ClNO P32297#Neuronal acetylcholine receptor subunit alpha-3 D0X4ZR DB01157 Trimetrexate small molecule approved 52128-35-5 369.4176 C19H23N5O3 P00378#Dihydrofolate reductase Trimetrexate, a non-classical folate antagonist, is a synthetic inhibitor of the enzyme dihydrofolate reductase (DHFR). During DNA synthesis and cellular reproduction, folic acid is reduced to tetrahydrofolic acid by the enzyme folic acid reductase. By interfering with the reduction of folic acid, trimetrexate interferes with tissue cell reproduction. Generally, the most sensitive cells to the antimetabolite effect of trimetrexate are those cells which are most actively proliferating such as malignant cells, dermal epithelium, buccal and intestinal mucosa, bone marrow, fetal cells, and cells of the urinary bladder. Because the proliferation of cells in malignant tissues is greater than in most normal tissues, trimetrexate may impair the growth of the malignant tissues without causing irreversible damage to normal tissues. Due to very serious and potentially life-threatening side-effects of this drug, leucovorin must be co-administered for at least 72 hours after the last dose. D0Y7TS DB01158 Bretylium small molecule approved 59-41-6 243.163 C11H17BrN P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Bretylium is a bromobenzyl quaternary ammonium compound which selectively accumulates in sympathetic ganglia and their postganglionic adrenergic neurons where it inhibits norepinephrine release by depressing adrenergic nerve terminal excitability. Bretylium also suppresses ventricular fibrillation and ventricular arrhythmias. D02YYF DB01159 Halothane small molecule approved 151-67-7 197.382 C2HBrClF3 P23415#Glycine receptor subunit alpha-1@Q12791#Calcium-activated potassium channel subunit alpha-1@Q12879#Glutamate receptor ionotropic, NMDA 2A@P59768#Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2@P08100#Rhodopsin@Q9NPC2#Potassium channel subfamily K member 9@P28472#Gamma-aminobutyric acid receptor subunit beta-3@P20020#Plasma membrane calcium-transporting ATPase 1@P23634#Plasma membrane calcium-transporting ATPase 4 Halothane is a general inhalation anesthetic used for induction and maintenance of general anesthesia. It reduces the blood pressure and frequently decreases the pulse rate and depresses respiration. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. It does so by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential. D0D8VE DB01160 Dinoprost tromethamine small molecule approved 38562-01-5 475.616 C24H45NO8 DB01161 Chloroprocaine small molecule approved 133-16-4 270.755 C13H19ClN2O2 Q9Y5Y9#Sodium channel protein type 10 subunit alpha@Q01959#Sodium-dependent dopamine transporter Chloroprocaine is an ester type anesthetic agent indicated for production of local or regional anesthesia, particularly for oral surgery. Chloroprocaine (like cocaine) has the advantage of constricting blood vessels which reduces bleeding, unlike other local anesthetics like lidocaine. D07NAJ DB01162 Terazosin small molecule approved 63590-64-7 387.4329 C19H25N5O4 P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor@P01137#Transforming growth factor beta-1@Q12809#Potassium voltage-gated channel subfamily H member 2@Q9H252#Potassium voltage-gated channel subfamily H member 6@Q9NS40#Potassium voltage-gated channel subfamily H member 7 Terazosin is a quinazoline derivative alpha-1-selective adrenergic blockerLabel1,2. D0P9RF DB01164 Calcium chloride small molecule approved 10043-52-4 110.984 CaCl2 Q99584#Protein S100-A13 Calcium is the fifth most abundant element in the body and the major fraction is in the bony structure. Calcium plays important physiological roles, many of which are poorly understood. It is essential for the functional integrity of the nervous and muscular systems. It is necessary for normal cardiac function and is one of the factors that operates in the mechanisms involved in the coagulation of blood. DB01165 Ofloxacin small molecule approved 82419-36-1 361.3675 C18H20FN3O4 P11388#DNA topoisomerase 2-alpha Ofloxacin is a quinolone/fluoroquinolone antibiotic. Ofloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Ofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. D03NHW DB01166 Cilostazol small molecule approved 73963-72-1 369.4607 C20H27N5O2 Q14432#cGMP-inhibited 3',5'-cyclic phosphodiesterase A Cilostazol reduces the symptoms of intermittent claudication, as indicated by an increased walking distance. Intermittent claudication is pain in the legs that occurs with walking and disappears with rest. The pain occurs due to reduced blood flow to the legs. D03VPC DB01167 Itraconazole small molecule approved 84625-61-6 705.633 C35H38Cl2N8O4 Q16850#Lanosterol 14-alpha demethylase@Q16850#Lanosterol 14-alpha demethylase Itraconazole is an imidazole/triazole type antifungal agent. Itraconazole is a highly selective inhibitor of fungal cytochrome P-450 sterol C-14 α-demethylation via the inhibition of the enzyme cytochrome P450 14α-demethylase. This enzyme converts lanosterol to ergosterol, and is required in fungal cell wall synthesis. The subsequent loss of normal sterols correlates with the accumulation of 14 α-methyl sterols in fungi and may be partly responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition. Itraconazole exhibits in vitro activity against Cryptococcus neoformans and Candida spp. Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans. D0V4IB DB01168 Procarbazine small molecule approved 671-16-9 221.2988 C12H19N3O P21397#Amine oxidase [flavin-containing] A@P27338#Amine oxidase [flavin-containing] B Procarbazine is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Procarbazine is cell-phase specific for the S phase of cell division. D08GYO DB01169 Arsenic trioxide small molecule approved 1327-53-3 197.84 As2O3 O14920#Inhibitor of nuclear factor kappa-B kinase subunit beta@Q16881#Thioredoxin reductase 1, cytoplasmic@P05412#Transcription factor AP-1@P24385#G1/S-specific cyclin-D1@P27361#Mitogen-activated protein kinase 3@P28482#Mitogen-activated protein kinase 1@P31749#RAC-alpha serine/threonine-protein kinase@P38936#Cyclin-dependent kinase inhibitor 1@Q13547#Histone deacetylase 1@P29590#Protein PML Arsenic Trioxide is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy. D07VIK DB01170 Guanethidine small molecule approved 55-65-2 198.3085 C10H22N4 P23975#Sodium-dependent noradrenaline transporter High blood pressure can cause the heart and arteries to not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled. Guanethidine works by decreasing the heart rate and relaxing the blood vessels so that blood can flow more easily through the body, thereby reducing these risks. It is a postganglionic sympathetic nerve terminal blocker that prevents the release of norepinephrine from nerve terminals. D0N3PE DB01171 Moclobemide small molecule approved 71320-77-9 268.739 C13H17ClN2O2 P27338#Amine oxidase [flavin-containing] B@P21397#Amine oxidase [flavin-containing] A@P21397#Amine oxidase [flavin-containing] A@P27338#Amine oxidase [flavin-containing] B A selective, reversible inhibitor of monoamine oxidase (MAO) which increases the 1. Besides its presence in sympathetic nerves, there is an abundant evidence that MAO-A is localized in noradrenergic neurons in the locus coeruleus and MAO-B is closely associated with serotonergic neurons of the raphe nucleus 1. D01ZSO DB01172 Kanamycin small molecule approved 59-01-8 484.4986 C18H36N4O11 P0A7S3#30S ribosomal protein S12 Kanamycin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses. D0YV1Q DB01173 Orphenadrine small molecule approved 83-98-7 269.3813 C18H23NO O15399#Glutamate receptor ionotropic, NMDA 2D@Q05586#Glutamate receptor ionotropic, NMDA 1@O60391#Glutamate receptor ionotropic, NMDA 3B@Q8TCU5#Glutamate receptor ionotropic, NMDA 3A@P70174#Histamine H1 receptor@P23975#Sodium-dependent noradrenaline transporter@Q9Y5Y9#Sodium channel protein type 10 subunit alpha Orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Orphenadrine is an anticholinergic with a predominantly central effect and only a weak peripheral effect. In addition, it has mild antihistaminic and local anaesthetic properties. Parkinson's syndrome is the consequence of a disturbed balance between cholinergic and dopaminergic neurotransmission in the basal ganglia caused by a decrease in dopamine. Orphenadrine restores the physiological equilibrium and has a favourable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. The effect is somewhat less on bradykinesia. D0D9FV DB01174 Phenobarbital small molecule approved 50-06-6 232.2353 C12H12N2O3 Q13002#Glutamate receptor ionotropic, kainate 2@P42262#Glutamate receptor 2@P43681#Neuronal acetylcholine receptor subunit alpha-4@O75469#Nuclear receptor subfamily 1 group I member 2@P36544#Neuronal acetylcholine receptor subunit alpha-7@Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B Phenobarbital, the longest-acting barbiturate, is used for its anticonvulsant and sedative-hypnotic properties in the management of all seizure disorders except absence (petit mal). D0Y7RW DB01175 Escitalopram small molecule approved 128196-01-0 324.3919 C20H21FN2O P31645#Sodium-dependent serotonin transporter@P11229#Muscarinic acetylcholine receptor M1@P70174#Histamine H1 receptor@P08908#5-hydroxytryptamine receptor 1A@P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P23975#Sodium-dependent noradrenaline transporter@Q01959#Sodium-dependent dopamine transporter Escitalopram belongs to a class of medications called selective serotonin re-uptake inhibitors (SSRIs). These agents cause an increase in serotonin levels in neuronal synapses by preventing the re-uptake of serotonin (5-HT) into the presynaptic terminals of serotonergic neurons.11,6,18,19 As compared to other SSRIs, it appears to have a relatively quick onset of effect due to its potency.14,15 D08RBC DB01176 Cyclizine small molecule approved 82-92-8 266.3807 C18H22N2 P70174#Histamine H1 receptor@P49888#Estrogen sulfotransferase Cyclizine is a piperazine-derivative antihistamine used as an antivertigo/antiemetic agent. Cyclizine is used in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. Additionally, it has been used in the management of vertigo in diseases affecting the vestibular apparatus. Although the mechanism by which cyclizine exerts its antiemetic and antivertigo effects has not been fully elucidated, its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone. It also possesses anticholinergic, antihistaminic, central nervous system depressant, and local anesthetic effects. D08HRJ DB01177 Idarubicin small molecule approved 58957-92-9 497.4939 C26H27NO9 P11388#DNA topoisomerase 2-alpha Idarubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Idarubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Idarubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific. D01XDL DB01178 Chlormezanone small molecule approved 80-77-3 273.736 C11H12ClNO3S P30536#Translocator protein Chlormezanone is a non-benzodiazepine muscle relaxant. It was discontinued worldwide in 1996 by its manufacturer due to confirmed serious and rare cutaneous reactions (toxic epidermal necrolysis). D0S1OE DB01179 Podofilox small molecule approved 518-28-5 414.4053 C22H22O8 P68366#Tubulin alpha-4A chain@Q7KQL5#Tubulin beta chain@P11388#DNA topoisomerase 2-alpha Podofilox, also called podophyllotoxin, is a purer and more stable form of podophyllin in which only the biologically active portion of the compound is present. Podofilox is used to remove certain types of warts on the outside skin of the genital areas. D0D4HN DB01180 Rescinnamine small molecule approved 24815-24-5 634.716 C35H42N2O9 P12821#Angiotensin-converting enzyme Used to treat hypertension. Rescinnamine inhibits angiotensin-converting enzyme. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex and general vasoconstriction, both of which lead to increases vascular resistance. By inhibiting angiotensin II, aldosterone reabsorption is decreased as well as vasoconstriction. This combined effect serves to decrease blood pressure. D0G8NJ DB01181 Ifosfamide small molecule approved 3778-73-2 261.086 C7H15Cl2N2O2P O75469#Nuclear receptor subfamily 1 group I member 2 Ifosfamide requires activation by microsomal liver enzymes to active metabolites in order to exert its cytotoxic effects. Activation occurs by hydroxylation at the ring carbon atom 4 to form the unstable intermediate 4-hydroxyifosfamide. This metabolite than rapidly degrades to the stable urinary metabolite 4-ketoifosfamide. The stable urinary metabolite, 4-carboxyifosfamide, is formed upon opening of the ring. These urinary metabolites have not been found to be cytotoxic. N, N-bis (2-chloroethyl)-phosphoric acid diamide (ifosphoramide) and acrolein are also found. The major urinary metabolites, dechloroethyl ifosfamide and dechloroethyl cyclophosphamide, are formed upon enzymatic oxidation of the chloroethyl side chains and subsequent dealkylation. It is the alkylated metabolites of ifosfamide that have been shown to interact with DNA. Ifosfamide is cycle-phase nonspecific. D02TLO DB01182 Propafenone small molecule approved 54063-53-5 341.444 C21H27NO3 Q14524#Sodium channel protein type 5 subunit alpha@Q12809#Potassium voltage-gated channel subfamily H member 2@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects, and a direct stabilizing action on myocardial membranes. It is used in the treatment of atrial and ventricular arrhythmias. It acts by inhibiting sodium channels to restrict the entry of sodium into cardiac cells resulting in reduced excitation. Propafenone has local anesthetic activity approximately equal to procaine. D0J2KV DB01183 Naloxone small molecule approved 465-65-6 327.3743 C19H21NO4 P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor@P16220#Cyclic AMP-responsive element-binding protein 1@O00206#Toll-like receptor 4@P23141#Liver carboxylesterase 1 Naloxone is an opioid receptor antagonist indicated in the reversal of opioid overdoses.7 Naloxone has a shorter duration of action than opioids and multiple doses may be required.3,7 The therapeutic window of naloxone is wide, as it has no effect if a patient has not taken opioids.4,7 Patients treated with naloxone may experience opioid withdrawal and a person administering naloxone should be aware that reversal of opioid overdoses may not resolve all the symptoms a patient is experiencing if other drugs are involved.7 D0X3FX DB01184 Domperidone small molecule approved 57808-66-9 425.911 C22H24ClN5O2 P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor Domperidone is a specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms. D0AV3G DB01185 Fluoxymesterone small molecule approved 76-43-7 336.4409 C20H29FO3 P10275#Androgen receptor@P04150#Glucocorticoid receptor@P80365#Corticosteroid 11-beta-dehydrogenase isozyme 2 Fluoxymesterone is a synthetic androgen, or male hormone, similar to testosterone. Fluoxymesterone works by attaching itself to androgen receptors; this causes it to interact with the parts of the cell involved in the making of proteins. It may cause an increase in the synthesis of some proteins or a decrease in the synthesis of others. These proteins have a variety of effects, including blocking the growth of some types of breast cancer cells, stimulating cells that cause male sexual characteristics, and stimulating the production of red blood cells. D0L2LS DB01186 Pergolide small molecule approved 66104-22-1 314.488 C19H26N2S P08908#5-hydroxytryptamine receptor 1A@P41595#5-hydroxytryptamine receptor 2B@P28223#5-hydroxytryptamine receptor 2A@P28221#5-hydroxytryptamine receptor 1D@P28222#5-hydroxytryptamine receptor 1B@P28335#5-hydroxytryptamine receptor 2C@P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor Pergolide stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1 and D5 subreceptors and are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3 and D4 subreceptors and has been associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2 and D3 receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2 stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2 stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2- and D3-receptors. It also exhibits agonist activity on dopamine D4, D1, and D5, 5-hydroxytryptamine (5-HT)1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, α2A-, α2B-, α2C-, α1A-, α1B-, and α1D-adrenergic receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2A agonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion. Pergolide also causes transient increases in somatotropin (growth hormone) secretion and decreases in luteinizing hormone (LH) concentrations. D04JCN DB01187 Iophendylate small molecule approved 99-79-6 416.3368 C19H29IO2 Iophendylate is a myelographic oil-ester initially introduced for use in small amounts (1-2cc) for locating spinal tumors. Later, it was found to cause adhesive arachnoiditis. Because these substances are hyperbaric once they were placed in the subarachnoid space they would migrate to the distal portion, where they remained, producing progressive scarring. D0G2KD DB01188 Ciclopirox small molecule approved 29342-05-0 207.2689 C12H17NO2 P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Ciclopirox is a broad-spectrum antifungal medication that also has antibacterial and anti-inflammatory properties. Its main mode of action is thought to be its high affinity for trivalent cations, which inhibit essential co-factors in enzymes. Ciclopirox exhibits either fungistatic or fungicidal activity in vitro against a broad spectrum of fungal organisms, such as dermatophytes, yeasts, dimorphic fungi, eumycetes, and actinomycetes. In addition to its broad spectrum of action, ciclopirox also exerts antibacterial activity against many Gram-positive and Gram-negative bacteria. Furthermore, the anti-inflammatory effects of ciclopirox have been demonstrated in human polymorphonuclear cells, where ciclopirox has inhibited the synthesis of prostaglandin and leukotriene. Ciclopirox can also exhibit its anti-inflammatory effects by inhibiting the formation of 5-lipoxygenase and cyclooxygenase. D07GRH DB01189 Desflurane small molecule approved 57041-67-5 168.0378 C3H2F6O P23415#Glycine receptor subunit alpha-1@P42261#Glutamate receptor 1@Q09470#Potassium voltage-gated channel subfamily A member 1@P03886#NADH-ubiquinone oxidoreductase chain 1@P30049#ATP synthase subunit delta, mitochondrial Desflurane is a general inhalation anesthetic.22 It has a short duration of action as it is rapidly cleared.22 Patients should be counselled regarding the risks of malignant hyperthermia, perioperative hyperkalemia, respiratory adverse reactions in pediatric patients, QTc prolongation, hepatobiliary disorders, pediatric neurotoxicity, and postoperative agitation in children.22 D0H4GN DB01190 Clindamycin small molecule approved 18323-44-9 424.983 C18H33ClN2O5S Clindamycin exerts its bacteriostatic effect via inhibition of microbial protein synthesis.8 Clindamycin has a relatively short Tmax and half-life necessitating administration every six hours to ensure adequate antibiotic concentrations.20 D0R0ZL DB01191 Dexfenfluramine small molecule approved 3239-44-9 231.2573 C12H16F3N P31645#Sodium-dependent serotonin transporter@P28335#5-hydroxytryptamine receptor 2C Used to treat diabetes and obesity, Dexfenfluramine decreases caloric intake by increasing serotonin levels in the brain’s synapses. Dexfenfluramine acts as a serotonin reuptake inhibitor. It also causes release of serotonin from the synaptosomes. D0F9SG DB01192 Oxymorphone small molecule approved 76-41-5 301.3371 C17H19NO4 P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor Oxymorphone is a semi-synthetic opioid substitute for morphine. It is a potent analgesic. Opioid analgesics exert their principal pharmacologic effects on the CNS and the gastrointestinal tract. The principal actions of therapeutic value are analgesia and sedation. Opioids produce respiratory depression by direct action on brain stem respiratory centers. The mechanism of respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation. D02NSF DB01193 Acebutolol small molecule approved 37517-30-9 336.4259 C18H28N2O4 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor D0HD9K DB01194 Brinzolamide small molecule approved 138890-62-7 383.507 C12H21N3O5S3 P00918#Carbonic anhydrase 2@P00915#Carbonic anhydrase 1@P22748#Carbonic anhydrase 4@P35218#Carbonic anhydrase 5A, mitochondrial@P07451#Carbonic anhydrase 3 Used in the treatment of glaucoma, brinzolamide inhibits aqueous humor formation and reduces elevated intraocular pressure. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. Brinzolamide can decrease intraocular pressure by approximately 16-19% in patients with elevated intraocular pressure. D01MUR DB01195 Flecainide small molecule approved 54143-55-4 414.3427 C17H20F6N2O3 P35499#Sodium channel protein type 4 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha@Q12809#Potassium voltage-gated channel subfamily H member 2@Q92736#Ryanodine receptor 2 Flecainide inhibits the action of sodium and potassium ion channels in the heart, raising the threshold for depolarization and correcting arrhythmias.10 Flecainide has a long duration of action, allowing for once daily dosing.12 The therapeutic index is narrow.8 Patients should not take this medication if there is already structural heart disease or left ventricular systolic dysfunction.12 D03DAP DB01196 Estramustine small molecule approved 2998-57-4 440.403 C23H31Cl2NO3 Q92731#Estrogen receptor beta@P11137#Microtubule-associated protein 2@P78559#Microtubule-associated protein 1A Estramustine is an antineoplastic agent indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a combination of estradiol with nitrogen mustard. In vivo, the nitrogen-mustard moiety becomes active and participates in alkylation of DNA or other cellular components.. This causes DNA damage in rapidly dividing cancerous cells leading to cell death and ideally, tumor shrinkage. D03SRY DB01197 Captopril small molecule approved 62571-86-2 217.285 C9H15NO3S P12821#Angiotensin-converting enzyme@P08253#72 kDa type IV collagenase@P14780#Matrix metalloproteinase-9@P09960#Leukotriene A-4 hydrolase@P46663#B1 bradykinin receptor Captopril, an ACE inhibitor, antagonizes the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain its effects by causing increased vasodilation and decreased blood pressure. D0I0EG DB01198 Zopiclone small molecule approved 43200-80-2 388.808 C17H17ClN6O3 P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P47869#Gamma-aminobutyric acid receptor subunit alpha-2@P34903#Gamma-aminobutyric acid receptor subunit alpha-3@P31644#Gamma-aminobutyric acid receptor subunit alpha-5@P30536#Translocator protein Zopiclone is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zopiclone is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex. Subunit modulation of the GABABZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zopiclone binds selectively to the brain alpha subunit of the GABA A omega-1 receptor. D0ZB7K DB01199 Tubocurarine small molecule approved 57-95-4 609.7312 C37H41N2O6 Q15822#Neuronal acetylcholine receptor subunit alpha-2@P46098#5-hydroxytryptamine receptor 3A@P22303#Acetylcholinesterase@P36544#Neuronal acetylcholine receptor subunit alpha-7 Not Available D05HSC DB01200 Bromocriptine small molecule approved 25614-03-3 654.595 C32H40BrN5O5 P21728#D(1A) dopamine receptor@P08913#Alpha-2A adrenergic receptor@P41595#5-hydroxytryptamine receptor 2B@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor@P28222#5-hydroxytryptamine receptor 1B Bromocriptine stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1 and D5 subreceptors, which are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3 and D4 subreceptors, which are associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2 and D3 receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2 stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2 stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2-receptors. It also exhibits agonist activity (in order of decreasing binding affinity) on 5-hydroxytryptamine (5-HT)1D, dopamine D3, 5-HT1A, 5-HT2A, 5-HT1B, and 5-HT2C receptors, antagonist activity on α2A-adrenergic, α2C, α2B, and dopamine D1 receptors, partial agonist activity at receptor 5-HT2B, and inactivates dopamine D4 and 5-HT7 receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2A agonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion making bromocriptine an effective agent for treating disorders associated with hypersecretion of prolactin. Pulmonary fibrosis may be associated bromocriptine’s agonist activity at 5-HT1B and 5-HT2B receptors. D06YFA DB01201 Rifapentine small molecule approved 61379-65-5 877.0307 C47H64N4O12 P0A8T7#DNA-directed RNA polymerase subunit beta' Rifapentine is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifampin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency. D0G9IU DB01202 Levetiracetam small molecule approved 102767-28-2 170.212 C8H14N2O2 Q00975#Voltage-dependent N-type calcium channel subunit alpha-1B@Q7L0J3#Synaptic vesicle glycoprotein 2A Levetiracetam appears to prevent seizure activity via the selective inhibition of hypersynchronized epileptiform burst firing without affecting normal neuronal transmission, though the exact mechanism through which this occurs is unclear.11,15 The therapeutic index of levetiracetam is wide,15,9 making it relatively unique amongst other anti-epileptic medications. D0E1XL DB01203 Nadolol small molecule approved 42200-33-9 309.4006 C17H27NO4 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor Nadolol is a nonselective beta adrenal receptor blocker that is used to lower blood pressure.8,9 It has a long duration of action as it is usually taken once daily and a wide therapeutic index as patients start at doses of 40mg daily but may be increased to doses as high as 240mg daily.8,9 Patients taking nadolol should not aburptly stop taking it as this may lead to exacerbation of ischemic heart disease.8,9 D05SHK DB01204 Mitoxantrone small molecule approved 65271-80-9 444.4809 C22H28N4O6 P11388#DNA topoisomerase 2-alpha Mitoxantrone has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2. D0R3JB DB01205 Flumazenil small molecule approved 78755-81-4 303.2884 C15H14FN3O3 P18507#Gamma-aminobutyric acid receptor subunit gamma-2@P31644#Gamma-aminobutyric acid receptor subunit alpha-5@P14867#Gamma-aminobutyric acid receptor subunit alpha-1 Flumazenil antagonizes the CNS effects produced by benzodiazepines, but does not antagonize the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, or general anesthetics) and does not reverse the effects of opioids. D0D5GD DB01206 Lomustine small molecule approved 13010-47-4 233.695 C9H16ClN3O2 Q9H169#Stathmin-4 Lomustine is an alkylating agent of the nitrosourea type. Lomustine and its metabolites interferes with the function of DNA and RNA. It is cell cycle–phase nonspecific. Cancers form when some cells within the body multiply uncontrollably and abnormally. These cells then spread and destroy nearby tissues. Lomustine acts by slowing this process down. It kills cancer cells by damaging the DNA (the genetic material inside the cells) and stops them from dividing. D04JPJ DB01208 Sparfloxacin small molecule approved 110871-86-8 392.3998 C19H22F2N4O3 P11388#DNA topoisomerase 2-alpha Sparfloxacin is a synthetic fluoroquinolone broad-spectrum antimicrobial agent in the same class as ofloxacin and norfloxacin. Sparfloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Sparfloxacin exerts its antibacterial activity by inhibiting DNA gyrase, a bacterial topoisomerase. DNA gyrase is an essential enzyme which controls DNA topology and assists in DNA replication, repair, deactivation, and transcription. Quinolones differ in chemical structure and mode of action from (beta)-lactam antibiotics. Quinolones may, therefore, be active against bacteria resistant to (beta)-lactam antibiotics. Although cross-resistance has been observed between sparfloxacin and other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to sparfloxacin. In vitro tests show that the combination of sparfloxacin and rifampin is antagonistic against Staphylococcus aureus. D0K6GZ DB01209 Dezocine small molecule approved 53648-55-8 245.3599 C16H23NO P35372#Mu-type opioid receptor@P41145#Kappa-type opioid receptor Dezocine is a parenteral narcotic analgesic possessing both agonist and antagonist activity. It is similar to morphine with respect to analgesic potency and onset and duration of action. The narcotic antagonist activity is greater than that of pentazocine. D0P6VV DB01210 Levobunolol small molecule approved 47141-42-4 291.3853 C17H25NO3 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor Levobunolol is an ophthalmic beta-blocker, equally effective at β(1)- and β(2)-receptor sites. Levobunolol reduces both elevated and normal IOP in patients with or without glaucoma. In patients with elevated IOP, levobunolol reduces mean IOP by approximately 25-40% from baseline. As the drug is a nonselective &beta-adrenergic blocking agent, it can produce both systemic pulmonary and cardiovascular effects following topical application to the eye. These effects include adverse pulmonary effects (eg. bronchoconstriction, increased airway resistance), and a decrease in blood pressure and heart rate. D00IUG DB01211 Clarithromycin small molecule approved 81103-11-9 747.9534 C38H69NO13 P0A7J6#50S ribosomal protein L10@Q12809#Potassium voltage-gated channel subfamily H member 2@Q9Y6L6#Solute carrier organic anion transporter family member 1B1@Q9NPD5#Solute carrier organic anion transporter family member 1B3 Clarithromycin is a macrolide antibiotic whose spectrum of activity includes many gram-positive (Staphylococcus aureus, S. pneumoniae, and S. pyogenes) and gram-negative aerobic bacteria (Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis), many anaerobic bacteria, some mycobacteria, and some other organisms including Mycoplasma, Ureaplasma, Chlamydia, Toxoplasma, and Borrelia. Other aerobic bacteria that clarithromycin has activity against include C. pneumoniae and M. pneumoniae. Clarithromycin has an in-vitro activity that is similar or greater than that of erythromycin against erythromycin-susceptible organisms. Clarithromycin is usually bacteriostatic, but may be bactericidal depending on the organism and the drug concentration. D0Z1ZM DB01212 Ceftriaxone small molecule approved 73384-59-5 554.58 C18H18N8O7S3 Q9NSA0#Solute carrier family 22 member 11@Q4U2R8#Solute carrier family 22 member 6@Q8TCC7#Solute carrier family 22 member 8@P46059#Solute carrier family 15 member 1 Ceftriaxone is a cephalosporin/cephamycin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms.11 Ceftriaxone has in vitro activity against gram-positive aerobic, gram-negative aerobic, and anaerobic bacteria.12 The bactericidal activity of ceftriaxone results from the inhibition of cell wall synthesis and is mediated through ceftriaxone binding to penicillin-binding proteins (PBPs).10 Ceftriaxone is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended-spectrum beta-lactamases.11 However, resistance to ceftriaxone usually occurs through beta-lactamase hydrolysis, altered PBPs, or reduced bacterial cell permeability.10 Ceftriaxone should not be mixed with or giving in the same IV line as diluents/products containing calcium as they may cause ceftriaxone to precipitate.11 Ceftriaxone use may also cause biliary sludge or gallbladder pseudolithiasis.11,2 D07ACT DB01213 Fomepizole small molecule approved 7554-65-6 82.1038 C4H6N2 P07327#Alcohol dehydrogenase 1A@P00325#Alcohol dehydrogenase 1B@P00326#Alcohol dehydrogenase 1C@P04040#Catalase Fomepizole is a competitive inhibitor of alcohol dehydrogenase, the enzyme that catalyzes the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites. Ethylene glycol is first metabolized to glycoaldehyde which then undergoes further oxidation to glycolate, glyoxylate, and oxalate. Glycolate and oxalate are primarily responsible for metabolic acidosis and renal damage seen in ethylene glycol toxicity. {01}{03} Methanol is first metabolized to formaldehyde and then undergoes subsequent oxidation via formaldehyde dehydrogenase to become formic acid. It is formic acid that is primarily responsible for the metabolic acidosis and visual disturbances that are associated with methanol poisoning. D02NJA DB01214 Metipranolol small molecule approved 22664-55-7 309.4006 C17H27NO4 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor Metipranolol is a beta1 and beta2 (non-selective) adrenergic receptor-blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. Metipranolol is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. Metipranolol, when applied topically to the eye, has the action of reducing elevated, as well as normal, intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss and optic nerve damage. Metipranolol reduces intraocular pressure with little or no effect on pupil size or accommodation in contrast to the miosis which cholinergic agents are known to produce. D0L5FY DB01215 Estazolam small molecule approved 29975-16-4 294.738 C16H11ClN4 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Estazolam, a triazolobenzodiazepine derivative, is an oral hypnotic agent with anticonvulsant, hypnotic, and muscle relaxant properties. It has been shown in some cases to be more potent than diazepam or nitrazepam. D0P2CK DB01216 Finasteride small molecule approved 98319-26-7 372.5441 C23H36N2O2 P31213#3-oxo-5-alpha-steroid 4-dehydrogenase 2@P18405#3-oxo-5-alpha-steroid 4-dehydrogenase 1@P51857#3-oxo-5-beta-steroid 4-dehydrogenase Finasteride is an antiandrogenic compound that works by suppressing the production of serum and intraprostatic dihydrotestosterone (DHT) in men via inhibiting the enzyme responsible for the biosynthesis of DHT. The maximum effect of a rapid reduction in serum DHT concentration is expected to be observed 8 hours following administration of the first dose.13 In a single man receiving a single oral dose of 5 mg finasteride for up to 4 years, there was a reduction in the serum DHT concentrations by approximately 70% and the median circulating level of testosterone increased by approximately 10-20% within the physiologic range. 13 In a double-blind, placebo-controlled study, finasteride reduced intraprostatic DHT level by 91.4% but finasteride is not expected to decrease the DHT levels to castrate levels since circulating testosterone is also converted to DHT by the type 1 isoenzyme expressed in other tissues.1 It is expected that DHT levels return to normal within 14 days upon discontinuation of the drug.12 In a study of male patients with benign prostatic hyperplasia prior to prostatectomy, the treatment with finasteride resulted in an approximate 80% lower DHT content was measured in prostatic tissue removed at surgery compared to placebo.13 While finasteride reduces the size of the prostate gland by 20%, this may not correlate well with improvement in symptoms.8 The effects of finasteride are reported to be more pronounced in male patients with enlarged prostates (>25 mL) who are at the greatest risk of disease progression.1 D08IWD DB01217 Anastrozole small molecule approved 120511-73-1 293.3663 C17H19N5 P11511#Aromatase Anastrozole prevents the conversion of adrenal androgens (e.g. testosterone) to estrogen in peripheral and tumour tissues. As the growth of many breast cancers is stimulated and/or maintained by the presence of estrogen, anastrozole helps to treat these cancers by decreasing the levels of circulating estrogens.12,9 Anastrozole has a relatively long duration of action allowing for once daily dosing - serum estradiol is reduced by approximately 70% within 24 hours of beginning therapy with 1mg once daily, and levels remain suppressed for up to 6 days following cessation of therapy.10 D0W0BF DB01218 Halofantrine small molecule approved 69756-53-2 500.424 C26H30Cl2F3NO Q12809#Potassium voltage-gated channel subfamily H member 2@P46925#Plasmepsin-2 Halofantrine is a synthetic antimalarial which acts as a blood schizonticide. It is effective against multi drug resistant (including mefloquine resistant) P. falciparum malaria. D07MVK DB01219 Dantrolene small molecule approved 7261-97-4 314.257 C14H10N4O5 P21817#Ryanodine receptor 1 Dantrolene is classified as a direct-acting skeletal muscle relaxant. It is currently the only specific and effective treatment for malignant hyperthermia. In isolated nerve-muscle preparation, Dantrium has been shown to produce relaxation by affecting the contractile response of the muscle at a site beyond the myoneural junction. In skeletal muscle, Dantrium dissociates excitation-contraction coupling, probably by interfering with the release of Ca2+ from the sarcoplasmic reticulum. In the anesthetic-induced malignant hyperthermia syndrome, evidence points to an intrinsic abnormality of skeletal muscle tissue. In selected humans, it has been postulated that “triggering agents” (e.g.,general anesthetics and depolarizing neuromuscular blocking agents) produce a change within the cell which results in an elevated myoplasmic calcium. This elevated myoplasmic calcium activates acute cellular catabolic processes that cascade to the malignant hyperthermia crisis. It is hypothesized that addition of Dantrium to the “triggered” malignant hyperthermic muscle cell reestablishes a normal level of ionized calcium in the myoplasm. D0I8DD DB01220 Rifaximin small molecule approved 80621-81-4 785.8785 C43H51N3O11 P0A8V2#DNA-directed RNA polymerase subunit beta@O75469#Nuclear receptor subfamily 1 group I member 2 Rifaximin is a structural analog of rifampin and a non-systemic, gastrointestinal site-specific antibiotic. This non-systemic property of the drug is due to the addition of a pyridoimidazole ring, which renders it non-absorbable. Rifaximin acts by inhibiting bacterial ribonucleic acid (RNA) synthesis and contributes to restore intestinal microflora imbalance. Other studies have also shown rifaximin to be an pregnane X receptor (PXR) activator. As PXR is responsible for inhibiting the proinflammatory transcription factor NF-kappa B (NF-κB) and is inhibited in inflammatory bowel disease (IBD), rifaximin was proven to be effective for the treatment of IBS-D. D04ITO DB13145 Nedaplatin small molecule approved 95734-82-0 303.181 C2H8N2O3Pt Nedaplatin damages DNA and induces cell death in cancer cells 3. It also functions as a radiosensitizer, increasing the susceptibility of the affected cells to radiation therapy 2. D00UTD DB13146 Fluciclovine (18F) small molecule approved 222727-39-1 132.125 C5H8FNO2 Q9UM01#Y+L amino acid transporter 1@Q8WY07#Cationic amino acid transporter 3@P42261#Glutamate receptor 1@P42262#Glutamate receptor 2@P42263#Glutamate receptor 3@P48058#Glutamate receptor 4 Following intravenous administration, the tumor-to-normal tissue contrast is highest between 2 and 10 minutes after injection, with a 63% reduction in mean tumor uptake at 90 minutes after injection.6 The scanning time point should be evaluated carefully as an early scanning can present an increased blood pool and a late scanning will translate into an increased muscle uptake. These variations should always be considered in the image interpretation.8 DB13153 Levomenol small molecule approved 23089-26-1 222.372 C15H26O DB13154 Parachlorophenol small molecule approved 106-48-9 128.556 C6H5ClO P35499#Sodium channel protein type 4 subunit alpha Not Available DB13155 Esculin small molecule approved 531-75-9 340.284 C15H16O9 P10275#Androgen receptor Topically applied Esculine increases the “capillary density” (the number of capillaries open to flow per surface unit) and improves the morphological aspect of the smallest blood vessels. DB13156 Inosine pranobex small molecule approved 36703-88-5 1115.249 C52H78N10O17 Works by slowing the growth and spread of the virus in the body. It may also stimulate the immune system in the body, which helps to increase the body's ability to fight these infections. D0Q2QU DB13157 Sodium lauryl sulfoacetate small molecule approved 1847-58-1 330.41 C14H27NaO5S Sodium lauryl sulfoacetate acts as a wetting agent and surfactant in pharmaceutical preparations 1. It is currently used in enema-type laxatives. DB13158 Clobetasone small molecule approved 54063-32-0 408.89 C22H26ClFO4 P04150#Glucocorticoid receptor Topical corticosteroid like clobetasone are synthetic derivatives of cortisone which produce anti-inflammatory, antiproliferative, immunosuppressive and vasoconstrictor effects when applied to the skin. DB13163 Terpin hydrate small molecule approved 2451-01-6 190.283 C10H22O3 It acts to facilitate the removal of mucus from the respiratory tract. It prevents the exacerbation of excessive mucus production and secretion due to airway bacterial or viral infections, asthma or chronic bronchitis. Expectorants like terpin hydrate change mucus consistency and make coughing more productive. D07QKN DB13166 Zofenopril small molecule approved 81872-10-8 429.55 C22H23NO4S2 P12821#Angiotensin-converting enzyme Not Available DB13167 Alclofenac small molecule approved 22131-79-9 226.66 C11H11ClO3 P35354#Prostaglandin G/H synthase 2 Not Available D0C6OQ DB13170 Plecanatide small molecule approved 467426-54-6 1681.89 C65H104N18O26S4 P33402#Guanylate cyclase soluble subunit alpha-2 Food Effect Subjects who received either a low-fat, low calorie (LF-LC) meal or a high fat, high calorie (HF-HC) meal reported looser stools than fasted subjects up to 24 hours after a single dose of 9 mg (3 times the recommended dose). In clinical studies, Plecanatide was administered with or without food. D07FEC DB13178 Inositol small molecule approved 87-89-8 180.1559 C6H12O6 Inositol can stimulate glucose uptake in skeletal muscle cells which allows the decrease in blood sugar levels. This effect is later seen as a reduction in urine glucose concentration and indicates a decrease in high blood sugar levels.8 DB13179 Troleandomycin small molecule approved 2751-09-9 813.9684 C41H67NO15 O75469#Nuclear receptor subfamily 1 group I member 2@P60723#50S ribosomal protein L4@P49228#50S ribosomal protein L32 Troleandomycin, like other macrolide antibiotics, inhibits bacterial protein synthesis to prevent growth. D06IGU DB13180 Gluconic Acid small molecule approved 526-95-4 196.1553 C6H12O7 Used as part of electrolyte salts to maintain cation-anion balance in solutions. DB13209 Bismuth subnitrate small molecule approved 1304-85-4 1461.98 Bi5H9N4O22 Bismuth subnitrate acts as an antacid that exert protective effects on the gastric mucosa 1. In a double-blind endoscopically controlled study, bismuth substrate was demonstrated to be effective for symptomatic relief in duodenal ulcers 2. In the alcohol model of mucosal injury in the rat, bismuth substrate was shown to be cytoprotective 2. In a randomized clinical study consisting of patients with H. pylori-associated duodenal ulcer, adjunctive use of colloidal bismuth subnitrate in a short treatment regimen with omeprazole and clarithromycin resulted in improved eradication rate of H. pylori 3. DB13211 Guanoxan small molecule approved 2165-19-7 207.233 C10H13N3O2 Not Available DB13213 Butaperazine small molecule approved 653-03-2 409.59 C24H31N3OS Not Available DB13216 Oxolamine small molecule approved 959-14-8 245.326 C14H19N3O Not Available DB13218 Mandelic acid small molecule approved 90-64-2 152.149 C8H8O3 Not Available DB13219 Medifoxamine small molecule approved 32359-34-5 257.333 C16H19NO2 Not Available DB13221 Apronalide small molecule approved 528-92-7 184.239 C9H16N2O2 Not Available DB13222 Tilbroquinol small molecule approved 7175-09-9 238.084 C10H8BrNO Not Available DB13225 Dibenzepin small molecule approved 4498-32-2 295.386 C18H21N3O Not Available D0P8AY DB13228 Flosequinan small molecule approved 76568-02-0 239.26 C11H10FNO2S Not Available D0MP1C DB13231 Calcium lactate small molecule approved 814-80-2 218.218 C6H10CaO6 Both components of calcium lactate, calcium ion and lactic acid, play essential roles in the human body as a skeletal element an energy source, respectively 4. DB13235 Perboric acid small molecule approved 14034-78-7 59.82 BHO3 No systemic effects are expected as it is highly unlikely that the substance will be systemically available.9 DB13245 Thiram small molecule approved 137-26-8 240.433 C6H12N2S4 Not Available DB13246 Quinupramine small molecule approved 31721-17-2 304.437 C21H24N2 Not Available DB13247 Pramiracetam small molecule approved 68497-62-1 269.389 C14H27N3O2 Not Available D0P7VJ DB13248 Phthalylsulfathiazole small molecule approved 85-73-4 403.43 C17H13N3O5S2 Not Available DB13249 Magnesium silicate small molecule approved 1343-88-0 100.387 MgO3Si Not Available DB13253 Proxibarbal small molecule approved 2537-29-3 226.232 C10H14N2O4 Not Available DB13256 Clothiapine small molecule approved 2058-52-8 343.87 C18H18ClN3S Not Available D0PX8L DB13257 Ferrous sulfate anhydrous small molecule approved 7720-78-7 151.908 FeO4S P69905#Hemoglobin subunit alpha@P02786#Transferrin receptor protein 1 Ferrous sulfate replenishes iron, an essential component in hemoglobin, myoglobin, and various enzymes. It replaces the iron that is usually found in hemoglobin and myoglobin. Iron participates in oxygen transport and storage, electron transport and energy metabolism, antioxidant and beneficial pro-oxidant functions, oxygen sensing, tissue proliferation and growth, as well as DNA replication and repair.6,9 DB13258 Etofamide small molecule approved 25287-60-9 427.28 C19H20Cl2N2O5 Not Available DB13259 Ethyl chloride small molecule approved 75-00-3 64.514 C2H5Cl Not Available D05KEZ DB13262 Aceclidine small molecule approved 827-61-2 169.224 C9H15NO2 Not Available DB13265 Hexobendine small molecule approved 54-03-5 592.686 C30H44N2O10 Not Available DB13267 Ritiometan small molecule approved 34914-39-1 286.33 C7H10O6S3 Not Available DB13268 Acetarsol small molecule approved 97-44-9 275.0903 C8H10AsNO5 Some reports indicate a certain infection remission with the use of acetarsol but this reports also demonstrate the absorption of systemic arsenic which can be physiologically dangerous.3 DB13269 Dichlorobenzyl alcohol small molecule approved 1777-82-8 177.02 C7H6Cl2O Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha@Q9NY72#Sodium channel subunit beta-3@Q8IWT1#Sodium channel subunit beta-4 In vitro studies with the combination of dichlorobenzyl alcohol and amylmetacresol have shown a virucidal against a number of viruses associated with the common cold which is observed by a reduction in the viral load.2 In clinical trials, administration of dichlorobenzyl alcohol lozenges has been shown to generate a reduced throat soreness and to provide pain relief and relief from difficulty in swallowing 5 minutes after administration. This effect can last for even 2 hours.7 The relief effect was shown to reach a steady-state after 45 minutes.8 DB13270 Dibekacin small molecule approved 34493-98-6 451.521 C18H37N5O8 Not Available DB13273 Sultopride small molecule approved 53583-79-2 354.47 C17H26N2O4S Not Available DB13274 Micronomicin small molecule approved 52093-21-7 463.576 C20H41N5O7 Not Available DB13277 Benziodarone small molecule approved 68-90-6 518.089 C17H12I2O3 Not Available DB13278 Bucetin small molecule approved 1083-57-4 223.272 C12H17NO3 Not Available DB13279 Carbocromen small molecule approved 804-10-4 361.438 C20H27NO5 Not Available DB13282 Benzododecinium small molecule approved 10328-35-5 304.541 C21H38N Not Available DB13284 Meticrane small molecule approved 1084-65-7 275.34 C10H13NO4S2 Not Available DB13286 Bumadizone small molecule approved 3583-64-0 326.396 C19H22N2O3 Not Available DB13288 Tromantadine small molecule approved 53783-83-8 280.412 C16H28N2O2 Not Available DB13292 Pimethixene small molecule approved 314-03-4 293.43 C19H19NS Not Available DB13306 Chlorquinaldol small molecule approved 72-80-0 228.07 C10H7Cl2NO Chlorquinaldol is bacteriocidal in both gram positive and gram negative bacteria. It is more effective in targeting gram positive bacteria, particularly staphylococci.1 DB13322 Hydrotalcite small molecule approved 12304-65-3 619.973 CH24Al2Mg6O24 Not Available DB13323 Trichloroethylene small molecule approved 79-01-6 131.388 C2HCl3 Not Available DB13337 Pheneticillin small molecule approved 147-55-7 364.42 C17H20N2O5S Not Available DB13345 Dihydroergocristine small molecule approved 17479-19-5 611.743 C35H41N5O5 P28222#5-hydroxytryptamine receptor 1B@P41595#5-hydroxytryptamine receptor 2B@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P21728#D(1A) dopamine receptor@P14416#D(2) dopamine receptor@P35462#D(3) dopamine receptor Dihydroergocristine has been shown to present effect on memory and cognition. This activity in the brain is been reported by an increase in glutathione in age-related brain states.2 The reported effect on serotonin and adrenergic receptors has also been correlated to an inhibition of platelet aggregation.8 It has also been reported that individuals exposed to dihydroergocristine may present an amphoteric vasoregulating activity either hypotensive in hypertensive individuals or hypertensive in hypotensive individuals.1 This action is performed by promoting a dilating action in the contracted arteries and a tonic action in the dilated arteries and arterioles.8 The vasoregulating effect causes an increase in cerebral blood flow and oxygen consumption by the brain, which correlates with the brain protective function of dihydroergocristine.2 In Alzheimer studies, dihydroergocristine reduced the amyloid-beta levels in different cell types.4 To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit Ergoloid mesylate. D09NNH DB13346 Bufexamac small molecule approved 2438-72-4 223.272 C12H17NO3 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2@Q9UBN7#Histone deacetylase 6@Q969S8#Histone deacetylase 10 Bufexamac is a topically-active anti-inflammatory agent that inhibits the cyclooxygenase enzyme. In cutaneous and deep experimental inflammation, topical administration of bufexamac exerted a dose-related anti-inflammatory effect 1. In guinea pigs, bufexamax was shown to be more active than topical acetylsalicylic acid 5% or phenylbutazone 5% in delaying the local increase in temperature resulting from UV exposure 1. Bufexamac is unlikely to have any effect on wound healing 1. D02HXS DB13381 Sodium feredetate small molecule approved 15708-41-5 367.047 C10H12FeN2NaO8 Not Available DB13421 Edoxudine small molecule approved 15176-29-1 256.258 C11H16N2O5 P0DOO6#DNA polymerase In reports, it has been indicated that at antivirally active doses, edoxudine is phosphorylated to a much greater extent by hepatitis-infected cells when compared to mock-infected cells. Once phosphorylated, edoxudine is more highly incorporated into viral DNA than cellular DNA. The level of incorporation into viral DNA highly seems to be correlated with the concentration of edoxudine. The suppression of viral DNA synthesis caused a shutoff of viral replication and the viral titration is significantly reduced.2The effect of edoxudine is also proven to reduce significantly the lesion area produced by the viral activity to an even 44% reduction.1 D0Y4MD DB13444 Ioxitalamic acid small molecule approved 28179-44-4 643.942 C12H11I3N2O5 Ioxitalamate presents a very large osmolality which is related to the presence of renal toxicity, vasodilatation, bradycardia and pulmonary hypertension. This large osmolality allows ioxitalamate to move slowly in the bowel allowing for analysis for later follow excretion in the feces.3 DB13501 Bendazac small molecule approved 20187-55-7 282.299 C16H14N2O3 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Bendazac principally demonstrates an antidenaturant action on proteins 1,2. This effect has been shown to inhibit the denaturation of various proteins like ocular lens proteins by heat, ultraviolet radiation, free radicals, and other chemicals 1,2. The medication may be administered to patients via a number of different formulations, including orally as the lysine salt, as eye drops, or even topical applications for the skin 1,2. DB13520 Metergoline small molecule approved 17692-51-2 403.526 C25H29N3O2 Q99250#Sodium channel protein type 2 subunit alpha Not Available DB13532 Cyclopenthiazide small molecule approved 742-20-1 379.87 C13H18ClN3O4S2 Not Available DB13583 Mephenesin small molecule approved 59-47-2 182.219 C10H14O3 Mephenesin reduced neuronal excitability leading to decreases action potentials to muscle fibers which ultimately produces a reduction in spasticity 2. DB13595 Almasilate small molecule approved 71205-22-6 280.445 Al2H2MgO9Si2 Various non-prescription antacid products are available to the general public to purchase and use as a treatment for relieving the occasional, limited, and non-severe sensation of heartburn (or acid indigestion) that may frequently be associated with stomach indigestion (or dyspepsia) or gastroesophageal reflux disease (when stomach contents may rise back up into the esophagus and cause a taste of acid in the back of the mouth, among other symptoms) 3. DB13615 Mifamurtide small molecule approved 838853-48-8 1277.515 C59H110N6NaO20P O00206#Toll-like receptor 4@Q9HC29#Nucleotide-binding oligomerization domain-containing protein 2 Mifamurtide stimulates the innate immunity by activating monocytes and macrophages. Within hours following administration of mifamurtide in healthy adults or patients with osteosarcoma NOS, elevated plasma levels of proinflammatory molecules, such as TNF-α, IL-6, and IL-1β, and other indicators of immune stimulation like C-reactive protein and neopterine were observed 2. In vivo administration of mifamurtide in rat and mouse model resulted in inhibition of tumour growth of lung metastasis, skin and liver cancer, and fibrosarcoma 5. In addition, increased disease-free survival rate was demonstrated when mifamurtide was given as an adjuvant in dog models of osteosarcoma and hemangiosarcoma. Administration of mifamurtide was associated with transient neutropenia, usually when used in conjunction with chemotherapy. Pronounced inflammatory responses are uncommon 5. D01NTX DB13620 Potassium gluconate small molecule approved 299-27-4 234.245 C6H11KO7 Potassium is an essential nutrient. It is the most abundant cation in intracellular fluid, where it plays a key role in maintaining cell function, especially in excitable cells such as skeletal muscles, the heart, and nerves 3. DB13624 Methoxyphenamine small molecule approved 93-30-1 179.2588 C11H17NO P07550#Beta-2 adrenergic receptor Not Available DB13628 Ethyl hydroxybenzoate small molecule approved 120-47-8 166.1739 C9H10O3 Not Available DB13657 Benorilate small molecule approved 5003-48-5 313.309 C17H15NO5 Not Available D08GJO DB13680 Naftazone small molecule approved 15687-37-3 215.212 C11H9N3O2 Not Available DB13682 Cefpirome small molecule approved 84957-29-9 514.577 C22H22N6O5S2 Not Available DB13707 Sodium tartrate small molecule approved 868-18-8 194.05 C4H4Na2O6 Not Available DB13711 Tritoqualine small molecule approved 14504-73-5 500.548 C26H32N2O8 Not Available DB13720 Diphemanil small molecule approved 15394-62-4 278.418 C20H24N P20309#Muscarinic acetylcholine receptor M3 Diphemanil Methylsulfate is a quaternary ammonium anticholinergic. It binds muscarinic acetycholine receptors and thereby decreases secretory excretion of stomach acids as well as saliva and sweat. DB13743 Sodium aurotiosulfate small molecule approved 33614-49-2 526.2 AuH4Na3O8S4 Not Available DB13747 Trolamine small molecule approved 102-71-6 149.1882 C6H15NO3 Acts as a surfactant or alkalizing agent to aid in emulsification and solubilizing of compounds or in raising the pH of a solution 1 DB13749 Magnesium gluconate small molecule approved 59625-89-7 450.629 C12H26MgO16 Magnesium is a cofactor in over 300 enzyme systems that regulate a variety of biochemical reactions in the body, including protein synthesis, muscle and nerve function, blood glucose control, and blood pressure regulation. Magnesium is necessary for energy production, oxidative phosphorylation, and glycolysis 9. DB13751 Glycyrrhizic acid small molecule approved 1405-86-3 822.942 C42H62O16 P28845#Corticosteroid 11-beta-dehydrogenase isozyme 1@P01375#Tumor necrosis factor@P42574#Caspase-3@Q00653#Nuclear factor NF-kappa-B p100 subunit@P19838#Nuclear factor NF-kappa-B p105 subunit Glycyrrhizic acid was reported to present antiallergic, antiviral and anti-inflammatory activities as well as improvements in glucose tolerance.1 DB13766 Lidoflazine small molecule approved 3416-26-0 491.627 C30H35F2N3O Not Available DB13781 Xamoterol small molecule approved 81801-12-9 339.392 C16H25N3O5 P08588#Beta-1 adrenergic receptor Not Available DB13783 Acemetacin small molecule approved 53164-05-9 415.83 C21H18ClNO6 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 The effect of acemetacin causes a weak reduction of prostaglandin synthesis which generates an anti-inflammatory and analgesic effect. The weak inhibition of prostaglandin reduces significantly the damage caused in the mucous membrane of the gastrointestinal tract. Studies have shown that acemetacin strongly inhibits the release of histamine from mast cells and the generation of hyperthermia. Acemetacin effect also causes changes in systolic and diastolic blood pressure as well as inhibition of platelet aggregation.2 DB13800 Calcium levulinate small molecule approved 591-64-0 270.294 C10H14CaO6 P0DP23#Calmodulin@P31415#Calsequestrin-1@P22676#Calretinin The relatively new calcium levulinate is produced from a direct reaction between L- or levulinic acid levulose and calcium hydroxide 3. The resultant calcium levulinate formulation, when used as a calcium supplement, possesses a high calcium content that is observed to be 14.8% higher than the content typically found in calcium lactate 3. Moreover, this formulation also demonstrates a high solubility of more than 30% at 25℃ 3. Furthermore, the calcium levulinate is believed to be non-toxic and non-allergic, making it especially suitable for injection or infusion administrations 3. Additionally, this levulinate formulation is reported as having a good taste, little irritation with a pH value of 7, and good stability such that no precipitation or deterioration occurs during use 3. Finally, this calcium levulinate formulation is also believed to have good compatibility with calcium lactate, calcium chloride, and other material complexes which allows the formulation to also complex effectively with a diverse variety of foodstuffs and pharmaceutical dosage forms 3. DB13801 Muzolimine small molecule approved 55294-15-0 272.13 C11H11Cl2N3O Not Available DB13813 Iodoform small molecule approved 75-47-8 393.732 CHI3 Iodoform exhibits antibacterial activities after topical application. In a comparative study of wound dressing agents, iodoform gauze exerted an antibacterial effect 3 hours after the start of bacterial growth of E. coli and subsequently maintained the strong antibacterial effectiveness 5. A study demonstrated that direct and indirect exposure to high concentrations of iodoform induces a cytotoxic effect on cultures of macrophages and epithelial cells in vitro, while cell proliferation was enhanced at low concentrations of iodoform 4. This cytotoxic effect of iodoform in root canals may further lead to long-term local irritation to follicles of permanent successors and formation of cyst-like radiolucent defects 4. DB13838 Noxytiolin small molecule approved 15599-39-0 120.17 C3H8N2OS Not Available DB13848 Fluorodopa (18F) small molecule approved 92812-82-3 214.183 C9H10FNO4 Not Available DB13851 Artemotil small molecule approved 75887-54-6 312.406 C17H28O5 Not Available DB13853 Anethole trithione small molecule approved 532-11-6 240.35 C10H8OS3 Anethol trithione (ATT) possesses a high lipophilicity (log P = 3.8) but an extremely low water solubility (0.38 ug/mL), which limits its dissolution and absorption 2,4. Furthermore, ATT is quickly metabolized into 4-hydroxy-anethole trithione (ATX, which demonstrates a similar pharmacological activity to ATT) by way of O-demethylation 2,4. As a consequence, the plasma concentration of ATT is usually fairly low, resulting in a limited oral bioavailability as well 2,4. Given this pharmacodynamic profile, there is continued interest and study in developing vehicles with which ATT can be administered in larger availabilities into the body 2,4. DB13854 Gamolenic acid small molecule approved 506-26-3 278.4296 C18H30O2 Gamolenic acid is converted to PGE1, which exhibits anti-inflammatory, antithrombotic, antiproliferative, and lipid-lowering effects 8. PGE1 also induces smooth muscle relaxation and vasodilation. Gamolenic acid is an essential component of membrane phospholipids, including the mitochondrial membrane, where it enhances the the integrity and the fluidity of the membrane 8. D0UE9X DB13858 Dimazole small molecule approved 95-27-2 293.43 C15H23N3OS Not Available DB13867 Fluticasone small molecule approved 90566-53-3 444.51 C22H27F3O4S P04150#Glucocorticoid receptor@P06401#Progesterone receptor@P47712#Cytosolic phospholipase A2@P08235#Mineralocorticoid receptor Systemically, in vitro experiments show Fluticasone furoate activates glucocorticoid receptors, inhibits nuclear factor kappa b, and inhibits lung eosinophilia in rats12,13,7. Fluticasone propionate performs similar activity but is not stated to affect nuclear factor kappa b11Label. Fluticasone propionate as a topical formulation is also associated with vasoconstriction in the skin10,3. D0LC6K DB13872 Lormetazepam small molecule approved 848-75-9 335.185 C16H12Cl2N2O2 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Lormetazepam is a benzodiazepine which reduces central nervous system (CNS) activity 2,1. It produces anxiolytic, muscle relaxant, sedative and hypnotic effects. Because it is a short-acting benzodiapine, it does not produce significant sedation after waking. DB13873 Fenofibric acid small molecule approved 42017-89-0 318.75 C17H15ClO4 Q07869#Peroxisome proliferator-activated receptor alpha@Q9NPA2#Matrix metalloproteinase-25@P37231#Peroxisome proliferator-activated receptor gamma@Q03181#Peroxisome proliferator-activated receptor delta@O75469#Nuclear receptor subfamily 1 group I member 2 Various clinical studies have shown that elevated levels of total cholesterol, low-desnsity-lipoprotein (LDL-C), and apolipoprotein B (apo B) - an LDL membrane complex - are associated with human atherosclerosis Label. Concurrently, decreased levels of high-density-lioprotein (HDL-C) and its transport complex, apolipoproteins apo AI and apo AII, are associated with the development of atherosclerosis Label. Furthermore, epidemiological investigations demonstrate that cardiovascular morbidity and mortality vary directly with the levels of total cholesterol, LDL-C, and triglycerides, and inversely with the level of HDL-C Label. DB13874 Enasidenib small molecule approved 1446502-11-9 473.383 C19H17F6N7O P48735#Isocitrate dehydrogenase [NADP], mitochondrial In a study involving adult patients with relapsed or refractory AML, overall response rate of 40.3% was achieved in enasidenib therapy which was associated with cellular differentiation and maturation, typically without evidence of aplasia 2. Enasidenib is not shown to cause QTc prolongation. DB13878 Pibrentasvir small molecule approved 1353900-92-1 1113.201 C57H65F5N10O8 Q5L478#Nonstructural protein 5A Pibrentasvir is a pan-genotypic . According to HCV replicon assays, pibrentasvir has EC50 values ranging from 0.08-4.6 nM agaisnt laboratory and clinical isolates from subtypes 1a, 1b, 2a, 2b, 3a, 4a, 4d, 5a, and 6a, or EC50 values of 0.5-4.3 pM against laboratory and clinical isolates from subtypes 1a, 1b, 2a, 2b, 3a, 4a, 4b, 4d, 5a, 6a, 6e and 6p Label. It is active against common resistance-conferring substitutions in HCV genotypes 1 to 6 that confers resistance and decreased therapeutic response from other NS5A inhibitors, inluding positions 24, 28, 30, 31, 58, 92, or 93 in NS5A Label,1. In a QT study, pibrentasvir is not shown to prolong the QTc interval. DB13879 Glecaprevir small molecule approved 1365970-03-1 838.87 C38H46F4N6O9S Q91RS4#NS3 protease In a biochemical assay studying clinical isolates of HCV genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, and 6a, glecaprevir displayed IC50 values ranging from 3.5 to 11.3 nM that resulted in inhibition of the proteolytic activity of recombinant NS3/4A enzymes. In HCV replicon assays, glecaprevir had median EC50 values of 0.08-4.6 nM against laboratory and clinical isolates from subtypes 1a, 1b, 2a, 2b, 3a, 4a, 4d, 5a, and 6a Label. In a QT study, glecaprevir is not shown to prolong the QTc interval. DB13882 Methyl nicotinate small molecule approved 93-60-7 137.136 C7H7NO2 Following topical administration, methyl nicotinate acts as a peripheral vasodilator to enhance local blood flow at the site of application. It induced vasodilation of the peripheral blood capillaries which are located in the dermal papillae of upper dermis layers adjacent to the epidermis–dermis junction 1. During tissue penetration at the dermis, methyl nicotinate is hydrolyzed to nicotinic acid 1. In human volunteers, topical administration of methyl nicotinate caused vasodilation-induced generalized cutaneous erythema 1. DB13908 Amylmetacresol small molecule approved 1300-94-3 178.275 C12H18O Q99250#Sodium channel protein type 2 subunit alpha The mixture of amylmetacresol throat lozenge medications markedly reduces the infectivity of certain infectious viruses in the throat and in cough droplets, thus reducing opportunities for person-to-person transmission 9. In addition, it relieves symptoms of sore throat/irritation of the throat 1, 2. DB13909 Bismuth subgallate small molecule approved 99-26-3 394.091 C7H5BiO6 Bismuth subgallate is a heavy metal salt that is relatively insoluble and poorly absorbed 4,14. As a result, systemic absorption is not necessary 14 or possibly even desired when the agent is administered orally or onto specific otorhinolaryngology and/or dermatologic wound sites where it can execute its pharmacologic action directly within the gastrointestinal lumen 14 to deodorize flatulence and stools or potentially elicit a hemostatic effect on wounds 4. DB13910 Valproate bismuth small molecule approved 60364-28-5 638.598 C24H45BiO6 Not Available DB13911 Phloxine B small molecule approved 18472-87-2 829.63 C20H2Br4Cl4Na2O5 Not Available DB13925 Dotatate gallium Ga-68 small molecule approved 1027785-90-5 1500.54 C65H87GaN14O19S2 P30874#Somatostatin receptor type 2 The overexpression of somatostatin receptor in tumor tissue has been widely studied and the usage of scintigraphy for the diagnostic of neuroendocrine tumors has been happening since the beggining of the 90s. The development of positron-emission tomography there has been an emerging and growing field for the discovery of tracer labeled somatostatin analogues like dotatate gallium 68.3 Even after all the reportes, the pharmacodynamic profile of dotatate gallium 68 has not been studied. DB13928 Semaglutide small molecule approved 910463-68-2 4113.641 C187H291N45O59 P43220#Glucagon-like peptide 1 receptor Semaglutide reduces HbA1c, systolic blood pressure, and body weight.6 After 12 weeks of treatment, semaglutide decreased fasting and postprandial glucose by increasing insulin production and decreasing glucagon secretion (which is normally associated with increases in blood sugar). Semaglutide also lowers fasting triglycerides and VLDL cholesterol, exerting beneficial effects on cardiovascular health.5,12 D02ULU DB13931 Netarsudil small molecule approved 1254032-66-0 453.542 C28H27N3O3 Q13464#Rho-associated protein kinase 1@O75116#Rho-associated protein kinase 2@P23975#Sodium-dependent noradrenaline transporter Aqueous humour flows out of the eye via two pathways: 1) the conventional trabecular pathway and 2) the unconventional uveoscleral pathway. And, although it has been shown that the conventional trabecular pathway accounts for most aqueous outflow due to various pathologies, most medications available for treating glaucoma target the uveoscleral pathway for treatment and leave the diseased trabecular pathway untreated and unhindered in its progressive deterioration and dysfunction 2. D04WYX DB13943 Testosterone cypionate small molecule approved 58-20-8 412.614 C27H40O3 P03372#Estrogen receptor@P10275#Androgen receptor@P08235#Mineralocorticoid receptor Administration of ester derivatives of testosterone as testosterone cypionate generates an increase in serum testosterone to levels reaching 400% from the baseline within 24 hours of administration. These androgen levels remain elevated for 3-5 days after initial administration.3 The continuous variation in plasma testosterone after intramuscular administration of testosterone cypionate results in fluctuations in mood and libido as well as some local inflammation.4 DB13944 Testosterone enanthate small molecule approved 315-37-7 400.594 C26H40O3 P03372#Estrogen receptor@P10275#Androgen receptor@P08235#Mineralocorticoid receptor Administration of ester derivatives of testosterone as testosterone enanthate generates an increase in serum testosterone to levels reaching 400% from the baseline within 24 hours of administration. These androgen levels remain elevated for 3-5 days after initial administration.5 Continuous administration of testosterone enanthate shows a significant suppression of dihydrotestosterone, serum PSA, HDL and FSH, as well as a slight increase in serum estradiol. The levels of dihydrotestosterone and FSH can remain suppressed even 14 days after treatment termination. There are no changes in mood and sexual activity by the presence of testosterone enanthate.6 DB13946 Testosterone undecanoate small molecule approved 5949-44-0 456.711 C30H48O3 P03372#Estrogen receptor@P10275#Androgen receptor@P08235#Mineralocorticoid receptor Once in circulation, testosterone undecanoate is cleaved to release testosterone, which mediates a range of biological actions. Testosterone is an endogenous male hormone that plays a key role in male sexual differentiation: it is involved in the regulation of hematopoiesis, body composition, and bone metabolism. As a hormone replacement therapy, testosterone undecanoate is an exogenous source of testosterone in males with hypogonadism. Testosterone therapy aims to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, and loss of muscle and bone mass.3 D02AXG DB13947 Testosterone enantate benzilic acid hydrazone small molecule approved 18625-33-7 624.866 C40H52N2O4 Not Available DB13949 Ferric cation small molecule approved 20074-52-6 55.845 Fe P07822#Iron(3+)-hydroxamate-binding protein FhuD@P02786#Transferrin receptor protein 1 When Fe3+ is converted to soluble Fe2+, it primarily exists in the circulation in the complex forms bound to protein (hemoprotein) as heme compounds (hemoglobin or myoglobin), heme enzymes, or nonheme compounds (flavin-iron enzymes, transferring, and ferritin) 1. Once converted, Fe2+ serves to support various biological functions. Iron promotes the synthesis of oxygen transport proteins such as myoglobin and hemoglobin, and the formation of heme enzymes and other iron-containing enzymes involved in electron transfer and redox reactions 1. It also acts as a cofactor in many non-heme enzymes including hydroxylases and ribonucleotide reductase 8. Iron-containing proteins are responsible in mediating antioxidant actions, energy metabolism, oxygen sensing actions, and DNA replication and repair 8. Saturation of transferrin from high concentrations of unstable iron preparations may elevate the levels of weakly transferrin-bound Fe3+, which may induce oxidative stress by catalyzing lipid peroxidation and reactive oxygen species formation 5. DB13952 Estradiol acetate small molecule approved 4245-41-4 314.4186 C20H26O3 Q92731#Estrogen receptor beta@O75469#Nuclear receptor subfamily 1 group I member 2@P43681#Neuronal acetylcholine receptor subunit alpha-4@Q15596#Nuclear receptor coactivator 2@Q99527#G-protein coupled estrogen receptor 1@P00846#ATP synthase subunit a@Q14457#Beclin-1@P37059#Estradiol 17-beta-dehydrogenase 2@P62508#Estrogen-related receptor gamma Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular effects 9. DB13953 Estradiol benzoate small molecule approved 50-50-0 376.488 C25H28O3 Q92731#Estrogen receptor beta@O75469#Nuclear receptor subfamily 1 group I member 2@P43681#Neuronal acetylcholine receptor subunit alpha-4@Q15596#Nuclear receptor coactivator 2@Q99527#G-protein coupled estrogen receptor 1@P00846#ATP synthase subunit a@Q14457#Beclin-1@P37059#Estradiol 17-beta-dehydrogenase 2@P62508#Estrogen-related receptor gamma Estradiol, the principal intracellular human estrogen, is substantially more active than its metabolites, estrone and estriol, at the cellular level. DB13954 Estradiol cypionate small molecule approved 313-06-4 396.5622 C26H36O3 Q92731#Estrogen receptor beta@O75469#Nuclear receptor subfamily 1 group I member 2@P43681#Neuronal acetylcholine receptor subunit alpha-4@Q15596#Nuclear receptor coactivator 2@Q99527#G-protein coupled estrogen receptor 1@P00846#ATP synthase subunit a@Q14457#Beclin-1@P37059#Estradiol 17-beta-dehydrogenase 2@P62508#Estrogen-related receptor gamma Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular effects 9. DB13955 Estradiol dienanthate small molecule approved 7732-97-0 496.732 C32H48O4 Q92731#Estrogen receptor beta@O75469#Nuclear receptor subfamily 1 group I member 2@P43681#Neuronal acetylcholine receptor subunit alpha-4@Q15596#Nuclear receptor coactivator 2@Q99527#G-protein coupled estrogen receptor 1@P00846#ATP synthase subunit a@Q14457#Beclin-1@P37059#Estradiol 17-beta-dehydrogenase 2@P62508#Estrogen-related receptor gamma Estradiol, the principal intracellular human estrogen, is substantially more active than its metabolites, estrone and estriol, at the cellular level. DB13956 Estradiol valerate small molecule approved 979-32-8 356.4984 C23H32O3 Q92731#Estrogen receptor beta@O75469#Nuclear receptor subfamily 1 group I member 2@P43681#Neuronal acetylcholine receptor subunit alpha-4@Q15596#Nuclear receptor coactivator 2@Q99527#G-protein coupled estrogen receptor 1@P00846#ATP synthase subunit a@Q14457#Beclin-1@P37059#Estradiol 17-beta-dehydrogenase 2@P62508#Estrogen-related receptor gamma Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular effects 11. DB13960 Bronopol small molecule approved 52-51-7 199.988 C3H6BrNO4 At concentrations of 12.5 to 50 μg/mL, bronopol mediated an inhibitory activity against various strains of Gram negative and positive bacteria in vitro 3. The bactericidal activity is reported to be greater against Gram-negative bacteria than against Gram-positive cocci 3. Bronopol was also demonstrated to be effective against various fungal species, but the inhibitory action is reported to be minimal compared to that of against bacterial species 3. The inhibitory activity of bronopol decreases with increasing pH of the media 3,9. Bronopol also elicits an anti-protozoal activity, as demonstrated with Ichthyophthirius multifiliis in vitro and in vivo 2. It is proposed that bronopol affects the survival of all free-living stages of I. multifiliis 2. DB13962 Calcium saccharate small molecule approved 5793-88-4 248.2 C6H8CaO8 Not Available DB13966 Isopropyl myristate small molecule approved 110-27-0 270.4507 C17H34O2 Isopropyl myristate is an emollient vehicle that is effective at enhancing the penetration of other medical agents that may be incorporated into the vehicle as active agents 7. In one study, a 50:50 isopropanol-isopropyl myristate binary enhancer synergistically increased the transport of estradiol across a two-layer human epidermis in vitro 2. DB13967 Patent Blue small molecule approved 25305-77-5 561.69 C27H33N2O7S2 P02768#Serum albumin Administration of patent blue has been reported to cause hypersensitivity reactions in approximately 1% of the patients. It also presents a localized blue coloration which has made patent blue a sensitive and specific option for the detection of micrometastatic cancer in lymph nodes.4 DB13970 Dioctyldimonium small molecule approved 20256-55-7 270.524 C18H40N Not Available DB13971 Vanadium small molecule approved 7440-62-2 50.9415 V Not Available DB13972 Racemethionine small molecule approved 59-51-8 149.211 C5H11NO2S Not Available DB13977 Potassium carbonate small molecule approved 584-08-7 138.2055 CK2O3 Not Available DB13982 Lutetium Lu-177 small molecule approved 14265-75-9 176.9438 Lu Not Available DB13985 Lutetium Lu 177 dotatate small molecule approved 437608-50-9 1609.55 C65H87LuN14O19S2 P30874#Somatostatin receptor type 2@P30872#Somatostatin receptor type 1@P32745#Somatostatin receptor type 3@P31391#Somatostatin receptor type 4@P35346#Somatostatin receptor type 5 Clinically significant myelosuppression occurred in less than 10% of patients in the Lutetium Lu 177 dotatate (177Lu-Dotatate) group in one clinical trial 2. According to an open label study involving 20 patients with somatostatin receptor-positive midgut carcinoid tumors, the treatment with did not result in any large changes in the mean QTc interval (i.e., >20 ms).8 Due to high expression of SSTR2, pancreas was the primary target in animal studies using a non-radioactive form of lutetium Lu 177 dotatate (lutetium Lu 175 dotatate) 8. D0DQ7V DB13987 Strontium chloride small molecule approved 10476-85-4 158.52 Cl2Sr As an active ingredient in a toothpaste formulation, strontium chloride and the rest of the toothpaste product that it is incorporated into is designed to come into contact with and topically coat the teeth 1,2,3 that are being brushed and is not supposed to be swallowed. The regular use of the toothpaste maintains protection that strontium chloride provides against tooth sensitivity despite the normal everyday wear, tear, and cleaning of teeth. DB13995 Ferric pyrophosphate citrate small molecule approved 1802359-96-1 1321.571 C18H24Fe4O42P6 P02792#Ferritin light chain@P02794#Ferritin heavy chain@P69905#Hemoglobin subunit alpha@P68871#Hemoglobin subunit beta Iron supplementation typically results in increases in serum iron, transferrin-bound iron, and iron-stored in the form of ferritin in hepatocytes and macrophages. The available iron is usually used in bone marrow for the synthesis of hemoglobin.8 DB13996 Magnesium acetate small molecule approved 142-72-3 142.393 C4H6MgO4 P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Not Available DB13997 Baloxavir marboxil small molecule approved 1985606-14-1 571.55 C27H23F2N3O7S P03433#Polymerase acidic protein Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease which prevents polymerase function and therefore influenza virus mRNA replication 5, 3. It has shown therapeutic activity against influenza A and B virus infections, including strains resistant to current antiviral agents 1. This drug inhibits an enzyme required for viral replication, thus rapidly treating flu virus infection 5, Label and alleviating the symptoms associated with infection. A single dose of this agent was shown to be superior to placebo in relieving influenza symptoms and superior to both oseltamivir and placebo drug in virologic outcomes (marked by decreased viral load) 1. The safety profile of Baloxavir marboxil compared favorably with that of oseltamivir, making it an effective treatment option for treatment of the flu virus, in one single dose 5, 1. D0O5AG DB14001 alpha-Tocopherol succinate small molecule approved 4345-03-3 530.79 C33H54O5 P09917#Arachidonate 5-lipoxygenase@O76054#SEC14-like protein 2@Q9UDX4#SEC14-like protein 3@P05771#Protein kinase C beta type@O75469#Nuclear receptor subfamily 1 group I member 2@P17252#Protein kinase C alpha type@P23743#Diacylglycerol kinase alpha@Q16760#Diacylglycerol kinase delta@Q13574#Diacylglycerol kinase zeta Of the eight separate variants of vitamin E, alpha-tocopherol is the predominant form of vitamin E in human and animal tissues, and it has the highest bioavailability 16. This is because the liver preferentially resecretes only alpha-tocopherol by way of the hepatic alpha-tocopherol transfer protein (alpha-TTP); the liver metabolizes and excretes all the other vitamin E variants, which is why blood and cellular concentrations of other forms of vitamin E other than alpha-tocopherol are ultimately lower 15. DB14002 D-alpha-Tocopherol acetate small molecule approved 58-95-7 472.7428 C31H52O3 Q9UDX4#SEC14-like protein 3@O76054#SEC14-like protein 2@O75469#Nuclear receptor subfamily 1 group I member 2@P05771#Protein kinase C beta type@P09917#Arachidonate 5-lipoxygenase@P17252#Protein kinase C alpha type In addition to any following information, owing to d-alpha-Tocopherol acetate's closely related chemical nature with alpha-Tocopherol acetate, please also refer to the drug information page for alpha-Tocopherol acetate for further data. DB14006 Choline salicylate small molecule approved 2016-36-6 241.287 C12H19NO4 Q9Y5K3#Choline-phosphate cytidylyltransferase B@P22303#Acetylcholinesterase@P49585#Choline-phosphate cytidylyltransferase A@O14939#Phospholipase D2@P06276#Cholinesterase@Q13393#Phospholipase D1@P36544#Neuronal acetylcholine receptor subunit alpha-7 This is an anti-inflammatory and antipyretic medication 11, 12. D05QPW DB14007 Pentetic acid small molecule approved 67-43-6 393.349 C14H23N3O10 There are reports in vivo of low stability of complexes of DPTA with uranium and neptunium which is being reported to cause deposition of the radionuclides into the tissues.5 In the case of plutonium, some preclinical studies have shown a very high urine elimination efficacy 1 hour after initial contamination. This efficacy is conserved for approximately 24 hours while the radiocontaminant is circulating. When the radionuclide is inhaled, it has been reported a DPTA-induced reduction of even 98% of the lung deposits. It is important to consider that pentetic acid can bind directly to other trace metals in the body which can cause deficiencies.3 DB14015 Sodium bisulfite small molecule approved 7631-90-5 104.061 HNaO3S Not Available DB14018 Bromotheophylline small molecule approved 10381-75-6 259.063 C7H7BrN4O2 Bromotheophylline diuretic action will produce an immediate increase in urination frequency. This effect aids in the relief of bloating and menstrual pain.1 This diuretic function is performed by the an increase in glomerular filtration and a potential effect in the tubular reabsorption as it is established that the administration of these agents produce a rise in the urinary concentration of sodium a chloride and thus, an increase in their rates of excretion.2 DB14019 Fosnetupitant small molecule approved 1703748-89-3 688.608 C31H35F6N4O5P P25103#Substance-P receptor DB14020 Benzoin small molecule approved 119-53-9 212.2439 C14H12O2 Not Available D0Z5KQ DB14033 Acetyl sulfisoxazole small molecule approved 80-74-0 309.34 C13H15N3O4S P0AC13#Dihydropteroate synthase Sulfisoxazole is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with action against most gram-positive and many gram-negative organisms. Many strains of an individual species may be resistant to this drugf. Sulfonamides inhibit the multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus 6. DB14048 Sodium zirconium cyclosilicate small molecule approved 17141-74-1 365.452 Na2O9Si3Zr Sodium zirconium cyclosilicate is capable of reducing serum potassium concentrations as quickly as one hour after ingestion and normokalaemia can be achieved typically within 24 to 48 hours.3,4 Sodium zirconium cyclosilicate does not affect serum calcium or magnesium concentrations, or urinary sodium excretion.3,4 A close correlation is observed between starting serum potassium levels and effect size; patients with higher starting serum potassium levels have greater reductions in serum potassium.3,4 As a consequence of the resultant reduction in serum potassium concentration, there is a reduction in urinary potassium excretion as well.3,4 In a study of healthy subjects given sodium zirconium cyclosilicate 5 or 10 grams daily for four days, a dose-dependent reduction in serum potassium concentration and total urinary potassium excretion were accompanied by mean increases in fecal potassium excretion.3,4 No statistically significant changes in urinary sodium excretion were observed.3,4 D03AZK DB14075 Imidurea small molecule approved 39236-46-9 388.297 C11H16N8O8 Not Available DB14078 Medronic acid small molecule approved 1984-15-2 176.0023 CH6O6P2 Not Available DB14082 Betiatide small molecule approved 103725-47-9 367.38 C15H17N3O6S Not Available DB14083 Bisphenol A diglycidyl ether small molecule approved 1675-54-3 340.4129 C21H24O4 Not Available DB14084 Butylparaben small molecule approved 94-26-8 194.2271 C11H14O3 Not Available DB14086 Cianidanol small molecule approved 154-23-4 290.2681 C15H14O6 Not Available DB14089 Dimercaptosuccinic acid small molecule approved 2418-14-6 182.218 C4H6O4S2 Not Available DB14096 1,2-icosapentoyl-sn-glycero-3-phosphoserine small molecule approved 842.064 C47H72NO10P Not Available DB14099 1,2-Distearoyllecithin small molecule approved 4539-70-2 790.161 C44H88NO8P Not Available DB14104 Linoleic acid small molecule approved 60-33-3 280.4455 C18H32O2 Not Available DB14105 Sodium 1,2-Dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) small molecule approved 200880-41-7 744.964 C38H74NaO10P Not Available DB14106 Tetrakis(2-methoxyisobutylisocyanide)copper(I) tetrafluoroborate small molecule approved 103694-84-4 602.99 C24H44BCuF4N4O4 Not Available DB14109 alpha-Arbutin small molecule approved 84380-01-8 272.253 C12H16O7 P10253#Lysosomal alpha-glucosidase Not Available DB14110 Butylene glycol small molecule approved 107-88-0 90.121 C4H10O2 Not Available DB14116 Silodrate small molecule approved 12408-47-8 380.832 Al2H2Mg2O12Si3 Not Available DB14120 Phenylethyl resorcinol small molecule approved 85-27-8 214.264 C14H14O2 Not Available DB14141 p-Phenylenediamine small molecule approved 106-50-3 108.144 C6H8N2 Not Available DB14143 Distearyldimonium small molecule approved 14357-21-2 551.064 C38H80N Not Available DB14150 Chloric acid small molecule approved 7790-93-4 84.459 ClHO3 Not Available DB14151 Phosphorus small molecule approved 7723-14-0 30.9738 P Not Available DB14156 Synthetic camphor small molecule approved 76-22-2 152.2334 C10H16O Not Available DB14159 Oxidronic acid small molecule approved 15468-10-7 192.0 CH6O7P2 Not Available DB14173 Diazolidinylurea small molecule approved 78491-02-8 278.2194 C8H14N4O7 Not Available DB14174 Dipentamethylenethiuram disulfide small molecule approved 94-37-1 320.55 C12H20N2S4 Not Available DB14175 alpha-Amyl cinnamaldehyde small molecule approved 122-40-7 202.2921 C14H18O Not Available DB14176 Benzylparaben small molecule approved 94-18-8 228.247 C14H12O3 Not Available DB14177 Propylparaben small molecule approved 94-13-3 180.2005 C10H12O3 Not Available DB14178 Tetramethylthiuram monosulfide small molecule approved 97-74-5 208.36 C6H12N2S3 Not Available DB01221 Ketamine small molecule approved 6740-88-1 237.725 C13H16ClNO P29475#Nitric oxide synthase, brain@P25103#Substance-P receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor@P14416#D(2) dopamine receptor@P06276#Cholinesterase@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P41595#5-hydroxytryptamine receptor 2B@P28222#5-hydroxytryptamine receptor 1B Ketamine is a rapid-acting general anesthetic producing an anesthetic state characterized by profound analgesia, normal pharyngeal-laryngeal reflexes, normal or slightly enhanced skeletal muscle tone, cardiovascular and respiratory stimulation, and occasionally a transient and minimal respiratory depression. The anesthetic state produced by Ketamine has been termed as "dissociative anesthesia" in that it appears to selectively interrupt association pathways of the brain before producing somesthetic sensory blockade. It may selectively depress the thalamoneocortical system before significantly obtunding the more ancient cerebral centers and pathways (reticular-activating and limbic systems).2 D0UM7O DB01222 Budesonide small molecule approved 51333-22-3 430.5339 C25H34O6 P04150#Glucocorticoid receptor@P04083#Annexin A1 Budesonide is a glucocorticoid used to treat respiratory and digestive conditions by reducing inflammation.9,10,11,12,14,15,16 It has a wide therapeutic index, as dosing varies highly from patient to patient.9,10,11,12,14,15,16 Patients should be counselled regarding the risk of hypercorticism and adrenal axis suppression.9,10,11,12,14,15,16 D0Y7IU DB01223 Aminophylline small molecule approved 317-34-0 420.4264 C16H24N10O4 Q14432#cGMP-inhibited 3',5'-cyclic phosphodiesterase A@P30542#Adenosine receptor A1@P0DMS8#Adenosine receptor A3@Q92769#Histone deacetylase 2 Aminophylline is the ethylenediamine salt of theophylline. Theophylline stimulates the CNS, skeletal muscles, and cardiac muscle. It relaxes certain smooth muscles in the bronchi, produces diuresis, and causes an increase in gastric secretion. D03TYI DB01224 Quetiapine small molecule approved 111974-69-7 383.507 C21H25N3O2S P21728#D(1A) dopamine receptor@P20309#Muscarinic acetylcholine receptor M3@P08913#Alpha-2A adrenergic receptor@P35367#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor@P28222#5-hydroxytryptamine receptor 1B Quetiapine improves the positive and negative symptoms of schizophrenia and major depression by acting on various neurotransmitter receptors, such as the serotonin and dopamine receptors. In bipolar disorder, it improves both depressive and manic symptoms.1,8,9 D0H7KF DB01226 Mivacurium small molecule approved 133814-19-4 1029.2608 C58H80N2O14 Q15822#Neuronal acetylcholine receptor subunit alpha-2@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P06276#Cholinesterase Mivacurium is a short-acting, nondepolarizing skeletal neuromuscular blocking agent which is hydrolyzed by plasma cholinesterase. Mivacurium results in a blockade of neuromuscular transmission by binding competitively with cholinergic receptors on the motor end-plate to antagonize the action of acetylcholine. The neuromuscular block produced by mivacurium is readily antagonized by anticholinesterase agents. The deeper the level of neuromuscular block at reversal, the longer the time required for recovery of neuromuscular function and the greater the dose of anticholinesterase agent required. Because spontaneous recovery after mivacurium is rapid, routine reversal may not always result in a clinical benefit. D0OB2M DB01227 Levacetylmethadol small molecule approved 1477-40-3 353.4977 C23H31NO2 P35372#Mu-type opioid receptor@P30926#Neuronal acetylcholine receptor subunit beta-4@P32297#Neuronal acetylcholine receptor subunit alpha-3 Levomethadyl acetate (also known as LAAM) is a synthetic synthetic opioid analgesic with multiple actions quantitatively similar to those as morphine, the most prominent of which involve the central nervous system and organs composed of smooth muscle. However, levomethadyl acetate is more active and more toxic than morphine. The principal actions of therapeutic value are analgesia and sedation and detoxification or temporary maintenance in narcotic addiction. In this respect, the drug is similar to Methadone and also has structural similarities to it. The levomethadyl acetate abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe. DB01228 Encainide small molecule approved 66778-36-7 352.4699 C22H28N2O2 Q14524#Sodium channel protein type 5 subunit alpha Used to treat irregular heartbeats, encainide decreases excitability, conduction velocity, and automaticity as a result of slowed atrial, atrioventricular (AV) nodal, His-Purkinje, and intraventricular conduction. It causes a slight but significant prolongation of refractory periods in these tissues. The greatest effect is on the His-Purkinje system. Encainide decreases the rate of rise of the action potential without markedly affecting its duration. D06PAZ DB01229 Paclitaxel small molecule approved 33069-62-4 853.9061 C47H51NO14 P10415#Apoptosis regulator Bcl-2@O75469#Nuclear receptor subfamily 1 group I member 2@P10636#Microtubule-associated protein tau DB01230 Pemoline small molecule approved 2152-34-3 176.172 C9H8N2O2 Pemoline belongs to the group of medicines called central nervous system (CNS) stimulants. It is used to treat attention deficit hyperactivity disorder (ADHD). Pemoline stimulates the brain, probably by affecting neurotransmitters, the chemicals in the brain that nerves use to communicate with each other. D0D5GG DB01231 Diphenidol small molecule approved 972-02-1 309.4452 C21H27NO P08172#Muscarinic acetylcholine receptor M2@P11229#Muscarinic acetylcholine receptor M1@P20309#Muscarinic acetylcholine receptor M3 Diphenidol is used for control of nausea and vomiting. It has an antivertigo effect on the vestibular apparatus, inhibiting the chemoreceptor trigger zone to control nausea and vomiting, thus preventing motion sickness. D0W9VB DB01232 Saquinavir small molecule approved 127779-20-8 670.8408 C38H50N6O5 Saquinavir exerts its antiviral activity by inhibiting an enzyme critical for the HIV-1 viral lifecycle.6 Like other protease inhibitors, saquinavir has a propensity for participating in drug interactions - use caution when administering saquinavir to patients maintained on other pharmaceutical agents as pharmacodynamic and pharmacokinetic interactions are common.6 Saquinavir is known to increase the QTc-interval in otherwise healthy individuals, and should therefore be used with caution in patients maintained on other QTc-prolonging medications or for whom prolongation of the QTc-interval may be of particular consequence (e.g. patients with pre-existing heart disease).6 Careful and regular monitoring of patient bloodwork is recommended, as saquinavir has been associated with the development of metabolic complications (e.g. diabetes mellitus, hyperlipidemia) and worsening of pre-existing liver disease.6 D0WI3T DB01233 Metoclopramide small molecule approved 364-62-5 299.796 C14H22ClN3O2 Q13639#5-hydroxytryptamine receptor 4@P46098#5-hydroxytryptamine receptor 3A@P11229#Muscarinic acetylcholine receptor M1 Metoclopramide increases gastric emptying by decreasing lower esophageal sphincter (LES) pressure. It also exerts effects on the area postrema of the brain, preventing and relieving the symptoms of nausea and vomiting. In addition, this drug increases gastrointestinal motility without increasing biliary, gastric, or pancreatic secretions.17,18,19 D08VYV DB01234 Dexamethasone small molecule approved 50-02-2 392.4611 C22H29FO5 P04150#Glucocorticoid receptor@P51843#Nuclear receptor subfamily 0 group B member 1@P04083#Annexin A1@P35228#Nitric oxide synthase, inducible@O75469#Nuclear receptor subfamily 1 group I member 2 Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.3 Dexamethasone's duration of action varies depending on the route.12,13,14,15,16,17,18,19,20,21 Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.3 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.3 D0IT2G DB01235 Levodopa small molecule approved 59-92-7 197.1879 C9H11NO4 P21728#D(1A) dopamine receptor@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor Levodopa is able to cross the blood-brain barrier while dopamine is notLabel,8. The addition of a peripheral dopa decarboxylase inhibitor prevents the conversion of levodopa to dopamine in the periphery so that more levodopa can reach the blood-brain barrierLabel,8. Once past the blood-brain barrier, levodopa is converted to dopamine by aromatic-L-amino-acid decarboxylaseLabel,8. D08HVR DB01236 Sevoflurane small molecule approved 28523-86-6 200.0548 C4H3F7O P23415#Glycine receptor subunit alpha-1@P42261#Glutamate receptor 1@P03886#NADH-ubiquinone oxidoreductase chain 1@Q96ER9#Mitochondrial potassium channel Sevoflurane induces muscle relaxation and reduces sensitivity by altering tissue excitability with a fast onset of action. It does so by decreasing the extent of gap junction-mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.6 Compared to halothane and isoflurane, sevoflurane has a shorter emergence time, as well as a shorter time to first analgesia.8 To reach an equilibrium between alveolar and arterial partial pressure, only a minimal amount of sevoflurane needs to be dissolved in blood.8 D0W6ZF DB01237 Bromodiphenhydramine small molecule approved 118-23-0 334.251 C17H20BrNO P70174#Histamine H1 receptor Bromodiphenhydramine is an antihistamine of the ethanolamine class. Ethanolamine antihistamines have significant antimuscarinic activity and produce marked sedation in most patients. In addition to the usual allergic symptoms, the drug also treats irritant cough and nausea, vomiting, and vertigo associated with motion sickness. It also is used commonly to treat drug-induced extrapyramidal symptoms as well as to treat mild cases of Parkinson's disease. Rather than preventing the release of histamine, as do cromolyn and nedocromil, Bromodiphenhydramine competes with free histamine for binding at HA-receptor sites. Bromodiphenhydramine competitively antagonizes the effects of histamine on HA-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Ethanolamine derivatives have greater anticholinergic activity than do other antihistamines, which probably accounts for the antidyskinetic action of Bromodiphenhydramine. This anticholinergic action appears to be due to a central antimuscarinic effect, which also may be responsible for its antiemetic effects, although the exact mechanism is unknown. D0Y5GK DB01238 Aripiprazole small molecule approved 129722-12-9 448.385 C23H27Cl2N3O2 P14416#D(2) dopamine receptor Aripiprazole has high affinity for serotonin type 2 (5HT2), dopamine type 2 (D2), alpha1 and 2 adrenergic, and H1 histaminergic receptorsLabel,1. It also acts on a number of other receptors with lower affinityLabel,1. The exact method by which aripiprazole's action on these receptors translates to a clinically relevant effect is not yet knownLabel. D0H3HM DB01239 Chlorprothixene small molecule approved 113-59-7 315.86 C18H18ClNS P21728#D(1A) dopamine receptor@P20309#Muscarinic acetylcholine receptor M3@P35367#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor@P28222#5-hydroxytryptamine receptor 1B@P41595#5-hydroxytryptamine receptor 2B Chlorprothixene is a typical antipsychotic drug of the thioxanthine class. It has a low antipsychotic potency (half to 2/3 of chlorpromazine). Chlorprothixene has not thoroughly demonstrated an antidepressant or analgesic effect but it has demonstrated antiemetic effects. It is used in the treatment of nervous, mental, and emotional conditions. Improvement in such conditions is thought to result from the effect of the medicine on nerve pathways in specific areas of the brain. Chlorprothixene has a similar side effect profile to chlorpromazine, though allergic side effects and liver damage are less frequent. D0B0CP DB01240 Epoprostenol small molecule approved 35121-78-9 352.4651 C20H32O5 Q16647#Prostacyclin synthase@Q9H244#P2Y purinoceptor 12@P43119#Prostacyclin receptor Epoprostenol has two major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally mediated brudycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension. No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying. No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol. D0V0IX DB01241 Gemfibrozil small molecule approved 25812-30-0 250.3334 C15H22O3 Q07869#Peroxisome proliferator-activated receptor alpha@Q9Y6L6#Solute carrier organic anion transporter family member 1B1@Q8TCC7#Solute carrier family 22 member 8@O94956#Solute carrier organic anion transporter family member 2B1@Q9NPD5#Solute carrier organic anion transporter family member 1B3 Gemfibrozil alters lipid metabolism to treat patients with hyperlipidemia.11 The duration of action requires twice daily dosing as the mean residence time of gemfibrozil is up to 9.6h in patients with chronic renal failure.7 Gemfibrozil has a wide therapeutic index as trials with twice the standard dose were not associated with severe side effects.8,11 Patients taking gemfibrozil may be at an increased risk of developing cholelithiasis and cholecystitis, as seen in patients taking clofibrate.11 D05VIX DB01242 Clomipramine small molecule approved 303-49-1 314.852 C19H23ClN2 P31645#Sodium-dependent serotonin transporter@P28223#5-hydroxytryptamine receptor 2A@P41595#5-hydroxytryptamine receptor 2B@P28335#5-hydroxytryptamine receptor 2C@P23975#Sodium-dependent noradrenaline transporter@P09211#Glutathione S-transferase P Clomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: α1 and β1 receptors are sensitized, α2 receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. D0ZS8P DB01243 Chloroxine small molecule approved 773-76-2 214.048 C9H5Cl2NO Chloroxine has an antibacterial action, inhibiting the growth of gram-positive as well as some gram-negative organisms. Also, chloroxine has shown some antifungal activity against certain dermatophytes and yeasts. DB01244 Bepridil small molecule approved 64706-54-3 366.5396 C24H34N2O O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A@O95180#Voltage-dependent T-type calcium channel subunit alpha-1H@Q9NY47#Voltage-dependent calcium channel subunit alpha-2/delta-2@P05023#Sodium/potassium-transporting ATPase subunit alpha-1@P51787#Potassium voltage-gated channel subfamily KQT member 1@P63316#Troponin C, slow skeletal and cardiac muscles@P0DP23#Calmodulin@Q01064#Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B@P54750#Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A@Q12809#Potassium voltage-gated channel subfamily H member 2 Bepridil is a calcium channel blocker that has well characterized anti-anginal properties and known but poorly characterized type 1 anti-arrhythmic and anti-hypertensive properties. It is not related chemically to other calcium channel blockers such as diltiazem hydrochloride, nifedipine and verapamil hydrochloride. D0Y4JJ DB01245 Decamethonium small molecule approved 156-74-1 258.4863 C16H38N2 Q15822#Neuronal acetylcholine receptor subunit alpha-2@P43681#Neuronal acetylcholine receptor subunit alpha-4@P17787#Neuronal acetylcholine receptor subunit beta-2@P22303#Acetylcholinesterase Decamethonium acts as a depolarizing muscle relaxant or neuromuscular blocking agent. It acts as an agonist of nicotinic acetycholine receptors in the motor endplate and causes depolarization. This class of drugs has its effect at the neuromuscular junction by preventing the effects of acetylcholine. Normally, when a nerve stimulus acts to contract a muscle, it releases acetylcholine. The binding of this acetylcholine to receptors causes the muscle to contract. Muscle relaxants play an important role in anesthesia even though they don't provide any pain relief or produce unconsciousness. D05QNO DB01246 Alimemazine small molecule approved 84-96-8 298.446 C18H22N2S P70174#Histamine H1 receptor Trimeprazine (also known as Alimemazine) is a tricyclic antihistamine, similar in structure to the phenothiazine antipsychotics, but differing in the ring-substitution and chain characteristics. Trimeprazine is in the same class of drugs as chlorpromazine (Thorazine) and trifluoperazine (Stelazine); however, unlike the other drugs in this class, trimeprazine is not used clinically as an anti-psychotic. It acts as an anti-histamine, a sedative, and an anti-emetic (anti-nausea). Trimeprazine is used principally as an anti-emetic, to prevent motion sickness or as an anti-histamine in combination with other medications in cough and cold preparations. Tricyclic antihistamines are also structurally-related to the tricyclic antidepressants, explaining the antihistaminergic adverse effects of these two drug classes and also the poor tolerability profile of tricyclic H1-antihistamines. DB01247 Isocarboxazid small molecule approved 59-63-2 231.2505 C12H13N3O2 P21397#Amine oxidase [flavin-containing] A@P27338#Amine oxidase [flavin-containing] B In vivo and in vitro studies demonstrated isocarboxazid-driven inhibition of MAO in the brain, heart, and liver. The reduced MAO activity, caused by isocarboxazid, results in an increased concentration of serotonin, epinephrine, norepinephrine, and dopamine in storage sites throughout the central nervous system (CNS) and sympathetic nervous system. The increase of one or more monoamines is the basis for the antidepressant activity of MAO inhibitors like isocarboxazid.1 D0I2VK DB01248 Docetaxel small molecule approved 114977-28-5 807.8792 C43H53NO14 Q9H4B7#Tubulin beta-1 chain@P11137#Microtubule-associated protein 2@P27816#Microtubule-associated protein 4@P10636#Microtubule-associated protein tau@P10415#Apoptosis regulator Bcl-2@O75469#Nuclear receptor subfamily 1 group I member 2 Docetaxel is a taxoid antineoplastic agent. It promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, docetaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis. D0O5WP DB01249 Iodixanol small molecule approved 92339-11-2 1550.1819 C35H44I6N6O15 Iodixanol is a contrast agent commonly used during coronary angiography, particularly in individuals with renal dysfunction, as it is believed to be less toxic to the kidneys than most other intravascular contrast agents. It is an imaging contrast agent with the same osmolality as blood (290mOsm/kg H20). D0Y4YG DB01250 Olsalazine small molecule approved 15722-48-2 302.239 C14H10N2O6 P51580#Thiopurine S-methyltransferase@P01579#Interferon gamma Olsalazine is an anti-inflammatory drug used in the treatment of Inflammatory Bowel Disease and Ulcerative Colitis. Olsalazine reduces the bowel inflammation, diarrhea (stool frequency), rectal bleeding, and abdominal pain. Olsalazine is thought to work like balsalazide, delivering mesalazine or 5-aminosalicylic acid past the small intestine to the large intestine to act on the site of disease. D00KRE DB01251 Gliquidone small molecule approved 33342-05-1 527.632 C27H33N3O6S Q09428#ATP-binding cassette sub-family C member 8@Q15842#ATP-sensitive inward rectifier potassium channel 8 Gliquidone is an anti-diabetic drug in the sulfonylurea class. In patients with diabetes mellitus, there is a deficiency or absence of a hormone manufactured by the pancreas called insulin. Insulin is the main hormone responsible for the control of sugar in the blood. Gliquidone is an antidiabetic medication which is used in those patients with adult maturity onset or non-insulin dependent diabetes (NIDDM). It works by lowering blood sugar levels by stimulating the production and release of insulin from the pancreas. It also promotes the movement of sugar from the blood into the cells in the body which need it. D06HBQ DB01253 Ergometrine small molecule approved 60-79-7 325.4048 C19H23N3O2 P35348#Alpha-1A adrenergic receptor Ergonovine belongs to the group of medicines known as ergot alkaloids. These medicines are usually given to stop excessive bleeding that sometimes occurs after abortion or a baby is delivered. They work by causing the muscle of the uterus to contract. DB01254 Dasatinib small molecule approved 302962-49-8 488.006 C22H26ClN7O2S P00519#Tyrosine-protein kinase ABL1@P12931#Proto-oncogene tyrosine-protein kinase Src@P07947#Tyrosine-protein kinase Yes@P29317#Ephrin type-A receptor 2@P06239#Tyrosine-protein kinase Lck Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor D0E6XR DB01255 Lisdexamfetamine small molecule approved 608137-32-2 263.3785 C15H25N3O Q96RJ0#Trace amine-associated receptor 1 Lisdexamfetamine dimesylate is a prodrug of d-amphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulating properties Label. This agent works primarily by inducing the release of the neurotransmitters dopamine and norepinephrine from their storage areas in presynaptic nerve terminals 10. Both of these transmitters contribute to alertness, increased concentration, in addition to effort and motivation. D00DEF DB01256 Retapamulin small molecule approved 224452-66-8 517.763 C30H47NO4S Q9A1X4#50S ribosomal protein L3 Retapamulin is a semisynthetic pleuromutilin antibiotic. This drug is usually bacteriostatic in action, but may become bactericidal at highed concentrations (when MBC is 1000 times higher than MIC). Retapamulin acts by selectively inhibiting the initiation of protein synthesis in bacteria at the level of bacterial 50S ribosome. D03UQM DB01259 Lapatinib small molecule approved 231277-92-2 581.058 C29H26ClFN4O4S P00533#Epidermal growth factor receptor@P04626#Receptor tyrosine-protein kinase erbB-2 Lapatinib is a small molecule and a member of the 4-anilinoquinazoline class of kinase inhibitors. An anti-cancer drug, lapatinib was developed by GlaxoSmithKline (GSK) as a treatment for solid tumours such as breast and lung cancer. It was approved by the FDA on March 13, 2007, for use in patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug capecitabine. D08CDI DB01260 Desonide small molecule approved 638-94-8 416.5073 C24H32O6 P04150#Glucocorticoid receptor Desonide is a synthetic nonfluorinated corticosteroid for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents. D02JNM DB01261 Sitagliptin small molecule approved 486460-32-6 407.3136 C16H15F6N5O P27487#Dipeptidyl peptidase 4 Sitagliptin inhibits DPP-4 which leads to increased levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide(GIP), decreased levels of glucagon, and a stronger insulin response to glucoseLabel,4,1,2. D0U2JP DB01262 Decitabine small molecule approved 2353-33-5 228.2053 C8H12N4O4 P26358#DNA (cytosine-5)-methyltransferase 1@Q9Y6K1#DNA (cytosine-5)-methyltransferase 3A@Q9UBC3#DNA (cytosine-5)-methyltransferase 3B D0X5XU DB01263 Posaconazole small molecule approved 171228-49-2 700.7774 C37H42F2N8O4 Posaconazole is an antifungal agent structurally related to itraconazole. It is a drug derived from itraconzaole through the replacement of the chlorine substituents with flourine in the phenyl ring, as well as hydroxylation of the triazolone side chain. These modifications enhance the potency and spectrum of activity of the drug. Posaconazole can be either fungicial or fungistatic in action. D07ABV DB01264 Darunavir small molecule approved 206361-99-1 547.664 C27H37N3O7S Darunavir is an inhibitor of the human immunodeficiency virus (HIV) protease, which prevents HIV viral replication.17 When administered with ritonavir in combination antiretroviral therapy, darunavir significantly decreases viral load and increases CD4 cell counts, decreasing the morbidity and mortality of HIV infection.2,5,8 D03IGH DB01265 Telbivudine small molecule approved 3424-98-4 242.2286 C10H14N2O5 Q05486#Protein P Telbivudine is a synthetic thymidine nucleoside analogue with activity against hepatitis B virus (HBV). Telbivudine is the unmodified β–L enantiomer of the naturally occurring nucleoside, thymidine. It undergoes phosphorylation via interaction with cellular kinases to form the active metabolite, telbivudine 5'-triphosphate. D0CL9S DB01267 Paliperidone small molecule approved 144598-75-4 426.4839 C23H27FN4O3 P21728#D(1A) dopamine receptor@P08913#Alpha-2A adrenergic receptor@P35367#Histamine H1 receptor@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor Paliperidone is an atypical antipsychotic developed by Janssen Pharmaceutica. Chemically, paliperidone is primary active metabolite of the older antipsychotic risperidone (paliperidone is 9-hydroxyrisperidone). The mechanism of action is unknown but it is likely to act via a similar pathway to risperidone. D0B3UJ DB01268 Sunitinib small molecule approved 557795-19-4 398.4738 C22H27FN4O2 P09619#Platelet-derived growth factor receptor beta@P17948#Vascular endothelial growth factor receptor 1@P10721#Mast/stem cell growth factor receptor Kit@P35968#Vascular endothelial growth factor receptor 2@P35916#Vascular endothelial growth factor receptor 3@P36888#Receptor-type tyrosine-protein kinase FLT3@P07333#Macrophage colony-stimulating factor 1 receptor@P16234#Platelet-derived growth factor receptor alpha@P08581#Hepatocyte growth factor receptor Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA on January 26, 2006. D0R0MW DB01273 Varenicline small molecule approved 249296-44-4 211.268 C13H13N3 P43681#Neuronal acetylcholine receptor subunit alpha-4@P36544#Neuronal acetylcholine receptor subunit alpha-7@P32297#Neuronal acetylcholine receptor subunit alpha-3@Q15825#Neuronal acetylcholine receptor subunit alpha-6@P17787#Neuronal acetylcholine receptor subunit beta-2 Varenicline is a partial nicotinic acetylcholine receptor agonist, designed to partially activate this system while displacing nicotine at its sites of action in the brain. D0LM4A DB01274 Arformoterol small molecule approved 67346-49-0 344.4049 C19H24N2O4 P07550#Beta-2 adrenergic receptor Arformoterol, the active (R,R)-enantiomer of formoterol, is a selective long-acting β2-adrenergic receptor agonist (beta2-agonist) that has two-fold greater potency than racemic formoterol (which contains both the (S,S) and (R,R)-enantiomers). The (S,S)-enantiomer is about 1,000-fold less potent as a β2-agonist than the (R,R)-enantiomer. Arformoterol seems to have little or no effect on β1-adrenergic receptors. D0D1DI DB01275 Hydralazine small molecule approved 86-54-4 160.1759 C8H8N4 Q16853#Membrane primary amine oxidase@Q16665#Hypoxia-inducible factor 1-alpha@P13674#Prolyl 4-hydroxylase subunit alpha-1 Hydralazine interferes with calcium transport to relax arteriolar smooth muscle and lower blood pressure.19 Hydralazine has a short duration of action of 2-6h.10 This drug has a wide therapeutic window, as patients can tolerate doses of up to 300mg.19 Patients should be cautioned regarding the risk of developing systemic lupus erythematosus syndrome.19 D0K1XK DB01278 Pramlintide small molecule approved 151126-32-8 3949.44 C171H267N51O53S2 P30988#Calcitonin receptor@O60894#Receptor activity-modifying protein 1@O60895#Receptor activity-modifying protein 2@O60896#Receptor activity-modifying protein 3 Pramlintide is a synthetic analog of amylin, a glucoregulatory hormone that is synthesized by pancreatic β-cells and released into the bloodstream, in a similar pattern as insulin, after a meal. Like insulin, amylin is deficient in individuals with diabetes. It is provided as an acetate salt. Pramlintide is a 37-amino acid polypeptide that differs structurally from human amylin by the replacement of alanine, serine, and serine at positions 25, 28, and 29 respectively with proline. D0C4AM DB01280 Nelarabine small molecule approved 121032-29-9 297.2673 C11H15N5O5 P09884#DNA polymerase alpha catalytic subunit D0B8UJ DB01282 Carbetocin small molecule approved 37025-55-1 988.161 C45H69N11O12S P30559#Oxytocin receptor Carbetocin is a drug used to control postpartum hemorrhage, bleeding after giving birth. It is sold under the trade name Duratocin. It is an analogue of oxytocin, and its action is similar to that of oxytocin; it causes contraction of the uterus. D08FJL DB01283 Lumiracoxib small molecule approved 220991-20-8 293.721 C15H13ClFNO2 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Lumiracoxib has a different structure from the standard COX-2 inhibitors (e.g. celecoxib). It more closely resembles the structure of diclofenac (one chlorine substituted by fluorine, the phenylacetic acid has another methyl group in meta position), making it a member of the arylalkanoic acid family of NSAIDs. It binds to a different site on the COX-2 receptor than the standard COX-2 inhibitors. It displays extremely high COX-2 selectivity. D04YMH DB01284 Tetracosactide small molecule approved 16960-16-0 2933.49 C136H210N40O31S Q01718#Adrenocorticotropic hormone receptor Cosyntropin exhibits the full corticosteroidogenic activity of natural ACTH. Various studies have shown that the biologic activity of ACTH resides in the N- terminal portion of the molecule and that the 1-20 amino acid residue is the minimal sequence retaining full activity. Partial or complete loss of activity is noted with progressive shortening of the chain beyond 20 amino acid residue. For example, the decrement from 20 to 19 results in a 70% loss of potency. The pharmacologic profile of Cosyntropin is similar to that of purified natural ACTH. It has been established that 0.25 mg of Cosyntropin will stimulate the adrenal cortex maximally and to the same extent as 25 units of natural ACTH. Cosyntropin has less immunogenic activity than ACTH because the amino acid sequence having most of the antigenic activity of ACTH, i.e., amino acids 25-39, is not present in cosyntropin. The extra-adrenal effects which natural ACTH and Cosyntropin have in common include increased melanotropic activity, increased growth hormone secretion and an adipokinetic effect. These are considered to be without physiological or clinical significance. DB01288 Fenoterol small molecule approved 13392-18-2 303.3529 C17H21NO4 P07550#Beta-2 adrenergic receptor@P08588#Beta-1 adrenergic receptor@P13945#Beta-3 adrenergic receptor Fenoterol is a beta agonist designed to open up the airways to the lungs by decreasing bronchconstriction. D04XEG DB01291 Pirbuterol small molecule approved 38677-81-5 240.2988 C12H20N2O3 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor D0SS4P DB01294 Bismuth subsalicylate small molecule approved 14882-18-9 362.0926 C7H5BiO4 Bismuth subsalicylate is an antacid and antimicrobial, gastroprotective, anti-secretory, and anti-inflammatory actions.1,2,4 It works to reduce the severity and incidence of flatulence and diarrhea, and consequently relieving gastrointestinal discomfort.2 In one study, bismuth subsalicylate was prevented traveler's diarrhea with a protection rate >60%.8 DB01296 Glucosamine small molecule approved 3416-24-8 179.1711 C6H13NO5 P01579#Interferon gamma@Q04206#Transcription factor p65 The administration of glucosamine, in theory, provides a building block towards the synthesis of glycosaminoglycans, slowing the progression of osteoarthritis and relieving symptoms of joint pain. Studies to this date examining the efficacy of glucosamine sulfate have been inconclusive. Glycosaminoglycans contribute to joint cartilage elasticity, strength, and flexibility.11 A systematic review of various studies and guidelines determined that modest improvements were reported for joint pain and function in patients taking glucosamine. A consistent joint space narrowing was observed, but with an unclear clinical significance.6 D07NSU DB01297 Practolol small molecule approved 6673-35-4 266.3361 C14H22N2O3 P08588#Beta-1 adrenergic receptor Practolol is a beta-adrenergic receptor antagonist that has been used in the emergency treatment of cardiac arrhythmias. Beta blockers inhibit normal epinephrine-mediated sympathetic actions, but have minimal effect on resting subjects. That is, they reduce the effect of excitement/physical exertion on heart rate and force of contraction and dilation of blood vessels. D0KD1U DB01298 Sulfacytine small molecule approved 17784-12-2 294.33 C12H14N4O3S P0AC13#Dihydropteroate synthase Sulfacytine is a short-acting sulfonamide. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus. D0T1GT DB01299 Sulfadoxine small molecule approved 2447-57-6 310.329 C12H14N4O4S Q27738#Dihydropteroate synthetase Sulfadoxine helps inhibit the enzyme dihydropteroate synthetase which is an enzyme necessary in the conversion of PABA to folic acid. As folic acid is vital to the synthesis, repair, and methylation of DNA which is vital to cell growth in Plasmodium falciparum. With this vital nutrient lacking, the parasite has difficulty in reproducing. DB01301 Rolitetracycline small molecule approved 751-97-3 527.5662 C27H33N3O8 P0A7X3#30S ribosomal protein S9 Not Available D05AFR DB01303 Oxtriphylline small molecule approved 4499-40-5 283.3268 C12H21N5O3 Q14432#cGMP-inhibited 3',5'-cyclic phosphodiesterase A@P27815#cAMP-specific 3',5'-cyclic phosphodiesterase 4A@P29274#Adenosine receptor A2a@P30542#Adenosine receptor A1@Q92769#Histone deacetylase 2 Oxtriphylline is a bronchodilator. Oxtriphylline works in several ways: it relaxes muscles in your lungs and chest to allow more air in, decreases the sensitivity of your lungs to allergens and other substances that cause inflammation, and increases the contractions of your diaphragm to draw more air into the lungs. D0B0SH DB01319 Fosamprenavir small molecule approved 226700-79-4 585.607 C25H36N3O9PS Fosamprenavir is hydrolyzed by cellular phosphatases to the antiretroviral protease inhibitor amprenavir. This hydrolysis allows for the slow release of amprenavir, reducing the number of pills a patient must take. D0F5MT DB01320 Fosphenytoin small molecule approved 93390-81-9 362.2739 C16H15N2O6P Q14524#Sodium channel protein type 5 subunit alpha Fosphenytoin is a water-soluble phenytoin prodrug used for the treatment of epileptic seizures. Following parenteral administration of fosphenytoin, fosphenytoin is converted to the anticonvulsant phenytoin by endogenous phosphatases. Each 1.5 mg of fosphenytoin sodium is equivalent to 1.0mg of phenytoin sodium (PE equivalents); care should be taken to calculate the dose required in PE equivalents properly. Serious adverse effects such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN), and hematopoietic complications may occur and indicate an alternate antiepileptic should be used. Withdrawal of fosphenytoin sodium may precipitate seizures and should be done gradually.6 D0J5YC DB01322 Kava small molecule approved 9000-38-8 232.275 C14H16O3 Not Available DB01324 Polythiazide small molecule approved 346-18-9 439.882 C11H13ClF3N3O4S3 P55017#Solute carrier family 12 member 3 As a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure D06TNG DB01325 Quinethazone small molecule approved 73-49-4 289.739 C10H12ClN3O3S Q13621#Solute carrier family 12 member 1@P55011#Solute carrier family 12 member 2@P55017#Solute carrier family 12 member 3@P00915#Carbonic anhydrase 1@P00918#Carbonic anhydrase 2 Quinethazone is a thiazide diuretic used to treat hypertension. It inhibits Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. D0J8ZA DB01326 Cefamandole small molecule approved 34444-01-4 462.503 C18H18N6O5S2 D6R448#Penicillin-binding protein 2 The parenteral prodrug formate ester cefamandole nafate is a broad-spectrum cephalosporin antibiotic. The bactericidal action of cefamandole results from inhibition of cell-wall synthesis. Cephalosporins have in vitro activity against a wide range of gram-positive and gram-negative organisms. D06YHL DB01327 Cefazolin small molecule approved 25953-19-9 454.507 C14H14N8O4S3 P02919#Penicillin-binding protein 1B@P27169#Serum paraoxonase/arylesterase 1@P60568#Interleukin-2@P40933#Interleukin-15 Cefazolin (also known as cefazoline or cephazolin) is a semi-synthetic first generation cephalosporin for parenteral administration. Cefazolin has broad-spectrum antibiotic action due to inhibition of bacterial cell wall synthesis. It attains high serum levels and is excreted quickly via the urine. D09KDN DB01328 Cefonicid small molecule approved 61270-58-4 542.566 C18H18N6O8S3 P02919#Penicillin-binding protein 1B@P24228#D-alanyl-D-alanine carboxypeptidase DacB Cefonicid is a second-generation cephalosporin administered intravenously or intramuscularly. Its bactericidal action results from inhibition of cell wall synthesis. It is used for urinary tract infections, lower respiratory tract infections, and soft tissue and bone infections. D01BQC DB01329 Cefoperazone small molecule approved 62893-19-0 645.67 C25H27N9O8S2 P02919#Penicillin-binding protein 1B@P24228#D-alanyl-D-alanine carboxypeptidase DacB@P0AEB2#D-alanyl-D-alanine carboxypeptidase DacA@P08506#D-alanyl-D-alanine carboxypeptidase DacC@Q07806#Penicillin-binding protein 1A Cefoperazone is a third generation cephalosporin antibiotic. Cefoperazone exerts its bactericidal effect by inhibiting the bacterial cell wall synthesis D0C2YB DB01330 Cefotetan small molecule approved 69712-56-7 575.619 C17H17N7O8S4 A0A0E1R3H3#Penicillin-binding protein 3 Cefotetan is a semisynthetic cephamycin antibiotic that is administered intravenously or intramuscularly. The drug is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative microorganisms. D0AP9T DB01331 Cefoxitin small molecule approved 35607-66-0 427.452 C16H17N3O7S2 P02919#Penicillin-binding protein 1B@P24228#D-alanyl-D-alanine carboxypeptidase DacB@P0AEB2#D-alanyl-D-alanine carboxypeptidase DacA@P0A3M6#Penicillin-binding protein 2B@P08506#D-alanyl-D-alanine carboxypeptidase DacC@Q8DR59#Penicillin-binding protein 1A@Q7CRA4#Penicillin-binding protein 1b Cefoxitin is a cephamycin antibiotic often grouped with the second-generation cephalosporins. It is active against a broad range of gram-negative bacteria including anaerobes. The methoxy group in the 7a position provides cefoxitin with a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative bacteria. D02VFC DB01332 Ceftizoxime small molecule approved 68401-81-0 383.403 C13H13N5O5S2 P02919#Penicillin-binding protein 1B@P08506#D-alanyl-D-alanine carboxypeptidase DacC Ceftizoxime is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative organisms. It has few side effects and is reported to be safe and effective in aged patients and in patients with hematologic disorders. D0Y7BD DB01333 Cefradine small molecule approved 38821-53-3 349.405 C16H19N3O4S Not Available D06KKS DB01336 Metocurine small molecule approved 5152-30-7 652.8189 C40H48N2O6 Q15822#Neuronal acetylcholine receptor subunit alpha-2@P08172#Muscarinic acetylcholine receptor M2 Not Available DB01337 Pancuronium small molecule approved 16974-53-1 572.8619 C35H60N2O4 Q15822#Neuronal acetylcholine receptor subunit alpha-2@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3 Pancuronium is a non-depolarising muscle relaxant similar to curare. It acts as a competitive acetylcholine antagonist on neuromuscular junctions, displacing acetylcholine (hence competitive) from its post-synaptic nicotinic acetylcholine receptors. It is, unlike suxamethonium, a non-depolarising agent, which means, that it causes no spontaneous depolarisations upon association with the nicotinic receptor in neuromuscular junction, thus producing no muscle fasciculations upon administration. Pancuronium has no hormonal activity. It exerts slight vagolytic activity (i.e. diminishing activity of the vagus nerve) and no ganglioplegic (i.e., blocking ganglions) activity. D0AA0L DB01338 Pipecuronium small molecule approved 68399-58-6 602.8912 C35H62N4O4 Q15822#Neuronal acetylcholine receptor subunit alpha-2@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3 Pipecuronium is a nondepolarizing neuromuscular blocking agent. Neuromuscular blocking agents produce skeletal muscle paralysis by blocking neural transmission at the myoneural junction. The paralysis is selective initially and usually appears in the following muscles consecutively: levator muscles of eyelids, muscles of mastication, limb muscles, abdominal muscles, muscles of the glottis, and finally, the intercostal muscles and the diaphragm. Neuromuscular blocking agents have no clinically significant effect on consciousness or the pain threshold. D0XX6Y DB01339 Vecuronium small molecule approved 86029-43-8 557.8274 C34H57N2O4 Q15822#Neuronal acetylcholine receptor subunit alpha-2 The principal pharmacologic effects demonstrated by vecuronium revolve around its competitive binding of cholinergic receptors located at motor end plates. This competitive binding results in muscle relaxant effects that are typically employed as an adjunct to general anesthesia. D0Z8HG DB01340 Cilazapril small molecule approved 88768-40-5 417.4986 C22H31N3O5 P12821#Angiotensin-converting enzyme Cilazapril inhibits the production angiotensin II. By doing so, it decreases sodium and water reabsorption (via aldosterone) and it decreases vasoconstriction. The combined effect of this is a decrease in vascular resistance, and therefore, blood pressure. The absolute bioavailability of cilazaprilat after oral administration of cilazapril is 57% based on urinary recovery data. (The absolute bioavailability of cilazaprilat after oral administration of cilazaprilat is 19%.) Ingestion of food immediately before the administration of cilazapril reduces the average peak plasma concentration of cilazaprilat by 29%, delays the peak by one hour and reduces the bioavailability of cilazaprilat by 14%. These pharmacokinetic changes have little influence on plasma ACE inhibition. D04GKO DB14180 Nickel sulfate small molecule approved 7786-81-4 154.756 NiO4S Not Available DB14182 Dichromate small molecule approved 13907-47-6 215.986 Cr2O7 Not Available DB14183 Geraniol small molecule approved 106-24-1 154.253 C10H18O Not Available DB14184 Cinnamaldehyde small molecule approved 14371-10-9 132.1592 C9H8O Not Available DB14185 Aripiprazole lauroxil small molecule approved 1259305-29-7 660.72 C36H51Cl2N3O4 P21728#D(1A) dopamine receptor@P20309#Muscarinic acetylcholine receptor M3@P08913#Alpha-2A adrenergic receptor@P35367#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor@P28222#5-hydroxytryptamine receptor 1B DB14186 Cinnamyl alcohol small molecule approved 4407-36-7 134.1751 C9H10O Not Available DB14187 Hydroxycitronellal small molecule approved 107-75-5 172.2646 C10H20O2 Not Available DB14188 Isoeugenol small molecule approved 97-54-1 164.204 C10H12O2 Not Available DB14189 Ethylenediamine small molecule approved 107-15-3 60.0983 C2H8N2 Not Available DB14191 Diphenylguanidine small molecule approved 102-06-7 211.268 C13H13N3 Not Available DB14193 Ditiocarb zinc small molecule approved 14324-55-1 361.948 C10H20N2S4Zn Not Available DB14194 Zinc dibutyldithiocarbamate small molecule approved 136-23-2 474.12 C18H36N2S4Zn Not Available DB14195 4-(Isopropylamino)diphenylamine small molecule approved 101-72-4 226.323 C15H18N2 Not Available DB14196 N-Cyclohexyl-N'-phenyl-1,4-phenylenediamine small molecule approved 101-87-1 266.388 C18H22N2 Not Available DB14197 Methylchloroisothiazolinone small molecule approved 26172-55-4 149.59 C4H4ClNOS Not Available DB14198 Quaternium-15 small molecule approved 4080-31-3 251.156 C9H16Cl2N4 Not Available DB14199 Bromothalonil small molecule approved 35691-65-7 265.936 C6H6Br2N2 Not Available DB14200 Thiohexam small molecule approved 95-33-0 264.41 C13H16N2S2 Not Available DB14201 2,2'-Dibenzothiazyl disulfide small molecule approved 120-78-5 332.47 C14H8N2S4 Not Available DB14202 Morpholinylmercaptobenzothiazole small molecule approved 102-77-2 252.35 C11H12N2OS2 Not Available DB14203 Disperse Blue 106 small molecule approved 68516-81-4 335.38 C14H17N5O3S Not Available DB14206 Cobalt chloride small molecule approved 7646-79-9 129.839 Cl2Co Not Available DB14212 Methylparaben small molecule approved 99-76-3 152.1473 C8H8O3 Not Available DB14476 DL-alpha-Tocopherol small molecule approved 10191-41-0 430.717 C29H50O2 Not Available DB14481 Calcium phosphate dihydrate small molecule approved 7789-77-7 172.086 CaH5O6P P41180#Extracellular calcium-sensing receptor@P27797#Calreticulin@Q99828#Calcium and integrin-binding protein 1@O75340#Programmed cell death protein 6@P30626#Sorcin@Q99653#Calcineurin B homologous protein 1@P09486#SPARC@P27824#Calnexin@P35556#Fibrillin-2@P04271#Protein S100-B Calcium phosphate reacts with acid in the stomach to raise the pH 3. In toothpaste it provides a source of calcium and phosphate ions to support remineralization of the teeth 1. As a supplement it provides a source of calcium and phospate, both of which are important ions in bone homeostasis. DB14482 Sodium ascorbate small molecule approved 134-03-2 198.106 C6H7NaO6 Not Available DB14483 Calcium ascorbate small molecule approved 5743-27-1 390.31 C12H14CaO12 Not Available DB14484 Magnesium ascorbate small molecule approved 15431-40-0 374.537 C12H14MgO12 Not Available DB14485 Zinc ascorbate small molecule approved 331242-75-2 415.61 C12H14O12Zn Not Available DB14486 Niacinamide ascorbate small molecule approved 1987-71-9 298.251 C12H14N2O7 Not Available DB14487 Zinc acetate small molecule approved 557-34-6 183.497 C4H6O4Zn P46663#B1 bradykinin receptor@P16455#Methylated-DNA--protein-cysteine methyltransferase@P04075#Fructose-bisphosphate aldolase A@P68104#Elongation factor 1-alpha 1@P06733#Alpha-enolase@O14556#Glyceraldehyde-3-phosphate dehydrogenase, testis-specific@P15531#Nucleoside diphosphate kinase A@C0H4Y6#Protein disulfide-isomerase@P30101#Protein disulfide-isomerase A3@Q06830#Peroxiredoxin-1 Zinc is involved in various aspects of cellular metabolism. It has been estimated that approximately 10% of human proteins may bind zinc, in addition to hundreds of proteins that transport and traffic zinc. It is required for the catalytic activity of more than 200 enzymes, and it plays a role in immune function wound healing, protein synthesis, DNA synthesis, and cell division. Zinc is an essential element for a proper sense of taste and smell and supports normal growth and development during pregnancy, childhood, and adolescence. It is thought to have antioxidant properties, which may be protective against accelerated aging and helps to speed up the healing process after an injury; however, studies differ as to its effectiveness. Zinc ions are effective antimicrobial agents even if administered in low concentrations 29. DB14488 Ferrous gluconate small molecule approved 299-29-6 446.139 C12H22FeO14 P02786#Transferrin receptor protein 1@Q9GZT9#Egl nine homolog 1@Q9BY41#Histone deacetylase 8@Q9NZD4#Alpha-hemoglobin-stabilizing protein@P69905#Hemoglobin subunit alpha@Q16595#Frataxin, mitochondrial@P02794#Ferritin heavy chain@P39748#Flap endonuclease 1@Q96FI4#Endonuclease 8-like 1@Q969S2#Endonuclease 8-like 2 The major activity of supplemental iron is in the prevention and treatment of iron deficiency anemia. Iron has putative immune-enhancing, anticarcinogenic and cognition-enhancing activities. DB14489 Ferrous succinate small molecule approved 10030-90-7 171.917 C4H4FeO4 P02786#Transferrin receptor protein 1@Q9GZT9#Egl nine homolog 1@Q9BY41#Histone deacetylase 8@Q9NZD4#Alpha-hemoglobin-stabilizing protein@P69905#Hemoglobin subunit alpha@Q16595#Frataxin, mitochondrial@P02794#Ferritin heavy chain@P39748#Flap endonuclease 1@Q96FI4#Endonuclease 8-like 1@Q969S2#Endonuclease 8-like 2 The major activity of supplemental iron is in the prevention and treatment of iron deficiency anemia. Iron has putative immune-enhancing, anticarcinogenic and cognition-enhancing activities. DB14490 Ferrous ascorbate small molecule approved 24808-52-4 406.077 C12H14FeO12 P02786#Transferrin receptor protein 1@Q9GZT9#Egl nine homolog 1@Q9BY41#Histone deacetylase 8@Q9NZD4#Alpha-hemoglobin-stabilizing protein@P69905#Hemoglobin subunit alpha@Q16595#Frataxin, mitochondrial@P02794#Ferritin heavy chain@P39748#Flap endonuclease 1@Q96FI4#Endonuclease 8-like 1@Q969S2#Endonuclease 8-like 2 The major activity of supplemental iron is in the prevention and treatment of iron deficiency anemia. Iron has putative immune-enhancing, anticarcinogenic and cognition-enhancing activities. DB14491 Ferrous fumarate small molecule approved 141-01-5 169.901 C4H2FeO4 P02786#Transferrin receptor protein 1@Q9GZT9#Egl nine homolog 1@Q9BY41#Histone deacetylase 8@Q9NZD4#Alpha-hemoglobin-stabilizing protein@P69905#Hemoglobin subunit alpha@Q16595#Frataxin, mitochondrial@P02794#Ferritin heavy chain@P39748#Flap endonuclease 1@Q96FI4#Endonuclease 8-like 1@Q969S2#Endonuclease 8-like 2 The major activity of supplemental iron is in the prevention and treatment of iron deficiency anemia. Iron has putative immune-enhancing, anticarcinogenic and cognition-enhancing activities. DB14496 Sodium molybdate small molecule approved 7631-95-0 205.93 MoNa2O4 Not Available DB14498 Potassium acetate small molecule approved 127-08-2 98.1423 C2H3KO2 P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Not Available DB14499 Potassium sulfate small molecule approved 7778-80-5 174.259 K2O4S P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Not Available DB14500 Potassium small molecule approved 7440-09-7 39.0983 K P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Potassium maintains an electrolyte gradient on cell surfaces, keeping at specific concentrations inside and outside of the cell; this impacts fluid and electrolyte balance, nerve transmission, muscle contraction, as well as cardiac and kidney function. Clinical evidence has associated potassium intake with lower blood pressure in adults, reducing the risk stroke and heart disease. Dietary potassium may exert beneficial effects on bone loss in the elderly and kidney stones. Consumption of white vegetables, which are normally high in potassium, is associated with a lower risk of stroke.9 D0RN2W DB14501 Ferrous glycine sulfate small molecule approved 14729-84-1 302.041 C4H10FeN2O8S P02786#Transferrin receptor protein 1@Q9GZT9#Egl nine homolog 1@Q9BY41#Histone deacetylase 8@Q9NZD4#Alpha-hemoglobin-stabilizing protein@P69905#Hemoglobin subunit alpha@Q16595#Frataxin, mitochondrial@P02794#Ferritin heavy chain@P39748#Flap endonuclease 1@Q96FI4#Endonuclease 8-like 1@Q969S2#Endonuclease 8-like 2 The major activity of supplemental iron is in the prevention and treatment of iron deficiency anemia. Iron has putative immune-enhancing, anticarcinogenic and cognition-enhancing activities. DB14502 Sodium phosphate, dibasic small molecule approved 7558-79-4 141.9588 HNa2O4P Sodium phosphate inceases fecal water content to increase mobility through the large intestine 1. DB14505 Sodium borate small molecule approved 1330-43-4 201.219 B4Na2O7 Boric acid exhibits minimal bacteriostatic and antifungal activities 4. Boric acid is likely to mediate antifungal actions at high concentrations over prolonged exposures 3. DB14506 Lithium hydroxide small molecule approved 1310-65-2 23.95 HLiO Not Available DB14507 Lithium citrate small molecule approved 919-16-4 209.92 C6H5Li3O7 O14732#Inositol monophosphatase 2@P29218#Inositol monophosphatase 1@P49841#Glycogen synthase kinase-3 beta@P42263#Glutamate receptor 3 Although lithium has been used for over 50 years in treatment of bipolar disorder, the mechanism of action is still unknown. Lithium's therapeutic action may be due to a number of effects, ranging from inhibition of enzymes such as glycogen synthase kinase 3, inositol phosphatases, or modulation of glutamate receptors. DB14509 Lithium carbonate small molecule approved 554-13-2 73.89 CLi2O3 O14732#Inositol monophosphatase 2@P29218#Inositol monophosphatase 1@P49841#Glycogen synthase kinase-3 beta@P42263#Glutamate receptor 3 Lithium's mechanism of action is still unknownLabel. Lithium's therapeutic action may be due to a number of effects, ranging from inhibition of enzymes such as glycogen synthase kinase 3, inositol phosphatases, or modulation of glutamate receptors3,4. DB14512 Mometasone furoate small molecule approved 83919-23-7 521.429 C27H30Cl2O6 P04150#Glucocorticoid receptor@P06401#Progesterone receptor Mometasone is a synthetic corticosteroid with an affinity for glucocorticoid receptors 22 times higher than that of dexamethasone2. Mometasone furoate also has a lower affinity to mineralocorticoid receptors than natural corticosteroids, making it more selective in its action2. Mometasone furoate diffuses across cell membranes to activate pathways responsible for reducing inflammationLabel1,2,3,12,13. DB14513 Magnesium small molecule approved 7439-95-4 26.321 H2Mg Magnesium is important for many biochemical processes and is therefore quite common in humans.5 The majority of magnesium is stored in the bones (>50%), while the remainder is stored in muscle, soft tissue, red blood cells and serum.1 This is functionally important since the bones behave as a magnesium exchange reservoir and help maintain healthy levels of magnesium.1 D0B8QB DB14517 Aluminium phosphate small molecule approved 7784-30-7 121.9529 AlO4P P02787#Serotransferrin@P05023#Sodium/potassium-transporting ATPase subunit alpha-1@P06870#Kallikrein-1@P05067#Amyloid beta A4 protein Not Available DB14518 Aluminum acetate small molecule approved 139-12-8 204.1136 C6H9AlO6 P02787#Serotransferrin@P05023#Sodium/potassium-transporting ATPase subunit alpha-1@P06870#Kallikrein-1@P05067#Amyloid beta A4 protein Not Available DB14520 Tetraferric tricitrate decahydrate small molecule approved 967.803 C18H32Fe4O31 P07822#Iron(3+)-hydroxamate-binding protein FhuD@P02786#Transferrin receptor protein 1 Tetraferric tricitrate decahydrate is an iron containing product indicated to treat iron deficiency anemia and hyperphosphatemia.7 It has a wide therapeutic index, as doses can be varied significantly between patients.7 Tetraferric tricitrate decahydrate has a long duration of action in the treatment of iron deficiency anemia, due to the slow loss of iron from the body, and a moderate duration of action in the treatment of hyperphosphatemia, due to its action being dependant on residence time in the gastrointestinal tract.7 Patients should be counselled regarding the risk of iron overload.7 DB14527 Chromic nitrate small molecule approved 13548-38-4 238.0108 CrN3O9 P00167#Cytochrome b5 Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Chromium increases insulin binding to cells, increases insulin receptor density and activates insulin receptor kinase leading to enhanced insulin sensitivity 2. In chromium deficiency, intravenous administration of chromium resulted in normalization of the glucose tolerance curve from the diabetic-like curve typical of chromium deficiency Label. DB14528 Chromium gluconate small molecule approved 33661-40-4 637.437 C18H33CrO21 P00167#Cytochrome b5 Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Chromium increases insulin binding to cells, increases insulin receptor density and activates insulin receptor kinase leading to enhanced insulin sensitivity 2. In chromium deficiency, intravenous administration of chromium resulted in normalization of the glucose tolerance curve from the diabetic-like curve typical of chromium deficiency Label. DB14529 Chromium nicotinate small molecule approved 64452-96-6 418.305 C18H12CrN3O6 P00167#Cytochrome b5 Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Chromium increases insulin binding to cells, increases insulin receptor density and activates insulin receptor kinase leading to enhanced insulin sensitivity 2. In chromium deficiency, intravenous administration of chromium resulted in normalization of the glucose tolerance curve from the diabetic-like curve typical of chromium deficiency Label. DB14530 Chromous sulfate small molecule approved 13825-86-0 148.05 CrO4S P00167#Cytochrome b5 Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Chromium increases insulin binding to cells, increases insulin receptor density and activates insulin receptor kinase leading to enhanced insulin sensitivity 2. In chromium deficiency, intravenous administration of chromium resulted in normalization of the glucose tolerance curve from the diabetic-like curve typical of chromium deficiency Label. DB14533 Zinc chloride small molecule approved 7646-85-7 136.315 Cl2Zn P46663#B1 bradykinin receptor@P16455#Methylated-DNA--protein-cysteine methyltransferase@P04075#Fructose-bisphosphate aldolase A@P68104#Elongation factor 1-alpha 1@P06733#Alpha-enolase@O14556#Glyceraldehyde-3-phosphate dehydrogenase, testis-specific@P15531#Nucleoside diphosphate kinase A@C0H4Y6#Protein disulfide-isomerase@P30101#Protein disulfide-isomerase A3@Q06830#Peroxiredoxin-1 Zinc is a cofactor in many enzymes and mediates a number of catalytic, structural, and regulatory roles in the body.6 It has a wide therapeutic index and long duration of action, as most zinc in the body is reabsorbed.2,10 Patients should be counselled regarding the risk of administration in patients with severe kidney dysfunction.11 DB14539 Hydrocortisone acetate small molecule approved 50-03-3 404.4966 C23H32O6 P04083#Annexin A1@P04150#Glucocorticoid receptor@P80365#Corticosteroid 11-beta-dehydrogenase isozyme 2@P14060#3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated. DB14540 Hydrocortisone butyrate small molecule approved 13609-67-1 432.557 C25H36O6 P04083#Annexin A1@P04150#Glucocorticoid receptor@P80365#Corticosteroid 11-beta-dehydrogenase isozyme 2@P14060#3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated. DB14541 Hydrocortisone cypionate small molecule approved 508-99-6 486.649 C29H42O6 P04083#Annexin A1@P04150#Glucocorticoid receptor@P80365#Corticosteroid 11-beta-dehydrogenase isozyme 2@P14060#3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated. DB14542 Hydrocortisone phosphate small molecule approved 3863-59-0 442.445 C21H31O8P P04083#Annexin A1@P04150#Glucocorticoid receptor@P80365#Corticosteroid 11-beta-dehydrogenase isozyme 2@P14060#3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated. DB14543 Hydrocortisone probutate small molecule approved 72590-77-3 488.613 C28H40O7 P04083#Annexin A1@P04150#Glucocorticoid receptor@P80365#Corticosteroid 11-beta-dehydrogenase isozyme 2@P14060#3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated. DB14544 Hydrocortisone valerate small molecule approved 57524-89-7 446.5763 C26H38O6 P04083#Annexin A1@P04150#Glucocorticoid receptor@P80365#Corticosteroid 11-beta-dehydrogenase isozyme 2@P14060#3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated. DB14545 Hydrocortisone succinate small molecule approved 2203-97-6 462.539 C25H34O8 Not Available DB14550 Gallium chloride Ga-67 small molecule approved 173.28 Cl3Ga Not Available DB14554 Dotatate small molecule approved 177943-88-3 1435.63 C65H90N14O19S2 Not Available DB14568 Ivosidenib small molecule approved 1448347-49-6 582.97 C28H22ClF3N6O3 O75874#Isocitrate dehydrogenase [NADP] cytoplasmic Ivosidenib is an antineoplastic agent that is effective in cancers with a susceptible IDH1 mutation, which indicates increased levels of oncometabolite D-2-hydroxyglutarate (D-2HG) in cancer cells.5 Ivosidenib decreases D-2HG levels in a dose-dependent manner by inhibiting the IDH1 enzyme. Ivosidenib inhibits both the mutant and wild-type IDH1 but does not inhibit IDH2.7 D07DCG DB14569 Tedizolid small molecule approved 856866-72-3 370.344 C17H15FN6O3 D08KBK DB14574 Cobalt small molecule approved 7440-48-4 58.9332 Co Not Available DB14575 Eslicarbazepine small molecule approved 104746-04-5 254.2839 C15H14N2O2 Q99571#P2X purinoceptor 4 Not Available D04QZD DB14583 Segesterone acetate small molecule approved 7759-35-5 370.489 C23H30O4 P10275#Androgen receptor@P06401#Progesterone receptor@P04150#Glucocorticoid receptor DB00873 Loteprednol small molecule approved 129260-79-3 394.889 C21H27ClO5 Not Available DB14598 Edetate calcium disodium anhydrous small molecule approved 62-33-9 374.268 C10H12CaN2Na2O8 Edetate calcium disodium is a polyvalent ion chelator used to remove lead from the body after lead poisoning.7 It has a wide therapeutic index, as overdoses must be well in excess of the therapeutic dose to show symptoms.7 It has a long duration of action, as doses are given at least a day apart.7 Patients should be counselled regarding the risk of increased intracranial pressure with intravenous infusions.7 DB14600 Edetate disodium anhydrous small molecule approved 139-33-3 336.2063 C10H14N2Na2O8 Edetate disodium anhydrous is a polyvalent ion chelator that reduces blood concentrations of calcium or digitalis.2,3 It has a long duration of action as patients are generally given 1 daily dose.2,3 The therapeutic index is wide, as high doses are generally well tolerated.2,3 Patients should be counselled regarding the risk of postural hypotension, effects of myocardial contractility, hypokalemia, hypomagnesemia, and hypoglycemia.2,3 DB14627 Oxyphenisatin acetate small molecule approved 115-33-3 401.418 C24H19NO5 Not Available DB14631 Prednisolone phosphate small molecule approved 302-25-0 440.429 C21H29O8P P04150#Glucocorticoid receptor@P04083#Annexin A1 Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.2 Prednisolone has a short duration of action as the half life is 2-4 hours.5,6 Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces.2 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.2 DB14632 Prednisolone tebutate small molecule approved 7681-14-3 458.587 C27H38O6 Not Available DB14638 Diloxanide furoate small molecule approved 3736-81-0 328.147 C14H11Cl2NO4 Diloxanide is a luminal amebicide, however the mechanism of action of diloxanide is unknown. Diloxanide destroys the trophozoites of E. histolytica that eventually form into cysts. The cysts are then excreted by persons infected with asymptomatic amebiasis. Diloxanide furoate is a prodrug, and is hydrolyzed in the gastrointestinal tract to produce diloxanide, the active ingredient. DB14642 Lypressin small molecule approved 50-57-7 1056.23 C46H65N13O12S2 P37288#Vasopressin V1a receptor@P30518#Vasopressin V2 receptor@P47901#Vasopressin V1b receptor Not Available D09PZZ DB14643 Methylprednisolone aceponate small molecule approved 86401-95-8 472.578 C27H36O7 Not Available DB14644 Methylprednisolone hemisuccinate small molecule approved 2921-57-5 474.55 C26H34O8 Methylprednisolone sodium succinate (the sodium salt of methylprednisolone hemisuccinate) has the same metabolic and anti-inflammatory actions as methylprednisolone. When given parenterally and in equimolar quantities, the two compounds are equivalent in biologic activity. DB14646 Prednisone acetate small molecule approved 125-10-0 400.471 C23H28O6 Not Available DB14649 Dexamethasone acetate small molecule approved 1177-87-3 434.4977 C24H31FO6 P04150#Glucocorticoid receptor@P04083#Annexin A1@P35228#Nitric oxide synthase, inducible@P51843#Nuclear receptor subfamily 0 group B member 1@O75469#Nuclear receptor subfamily 1 group I member 2 Not Available DB14650 Menadiol diphosphate small molecule approved 84-98-0 334.1557 C11H12O8P2 Not Available DB14655 Drostanolone propionate small molecule approved 521-12-0 360.538 C23H36O3 Dromostanolone is a synthetic androgen, or male hormone, similar to testosterone. Dromostanolone works by attaching itself to androgen receptors; this causes it to interact with the parts of the cell involved in the making of proteins. It may cause an increase in the synthesis of some proteins or a decrease in the synthesis of others. These proteins have a variety of effects, including blocking the growth of some types of breast cancer cells, stimulating cells that cause male sexual characteristics, and stimulating the production of red blood cells. DB14656 Chlorphenesin carbamate small molecule approved 886-74-8 245.66 C10H12ClNO4 Not Available DB14657 Paramethasone acetate small molecule approved 1597-82-6 434.504 C24H31FO6 Not Available DB14658 Chloramphenicol palmitate small molecule approved 530-43-8 561.54 C27H42Cl2N2O6 Not Available DB14669 Betamethasone phosphate small molecule approved 360-63-4 472.446 C22H30FO8P P04150#Glucocorticoid receptor@P04083#Annexin A1 Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.2 Betamethasone phosphate has a short duration of action as it is rapidly hydrolyzed to betamethasone.5 Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.2 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.2 DB14674 Estramustine phosphate small molecule approved 4891-15-0 520.38 C23H32Cl2NO6P Not Available DB14677 Gestonorone caproate small molecule approved 1253-28-7 414.586 C26H38O4 Not Available DB14702 Sodium metavanadate small molecule approved 13718-26-8 121.9295 NaO3V Not Available DB14703 Dexamethasone metasulfobenzoate small molecule approved 16978-57-7 576.63 C29H33FO9S Not Available DB14723 Larotrectinib small molecule approved 1223403-58-4 428.444 C21H22F2N6O2 P04629#High affinity nerve growth factor receptor@Q16620#BDNF/NT-3 growth factors receptor@Q16288#NT-3 growth factor receptor At doses that are nine-fold greater than the recommended adult dose, larotrectinib does not elicit any QTc interval prolongation that is clinically relevant Label. D07TOK DB14725 Cefamandole nafate small molecule approved 57268-80-1 490.51 C19H18N6O6S2 Not Available DB00781 Polymyxin B small molecule approved 1404-26-8 1203.499 C56H98N16O13 Polymyxin B is an antibiotic that disrupts the outer cell membrane of Gram negative bacteria, binds and neutralizes lipopolysaccharide, and inhibits respiration of Gram-negative bacterial cells4. Polymyxin B can be given by a number of routes to treat susceptible Gram negative bacterial infections4. Absorption of the drug is poor (though not necessary for most of its activity) and the excreted drug is unchanged by metabolic processes6,1. Polymyxin B is generally indicated for susceptible Gram negative infections of the urinary tract, meninges, and blood streamLabel. DB14753 Hydroxystilbamidine small molecule approved 495-99-8 280.331 C16H16N4O Hydroxystilbamidine isethionate is a member of the diamidines, a large family of biochemially and pharmacologically interesting compounds. It has a rather unusual combination of properties, exhibiting antitrypanosomal, antimaliarial, antifungal and carcinostatic activities. It also appears to act as an immunosuppressant. This drug may be used in the treatment of blastomycosis, a disease cased by the dimorphic fungus or mold called Blastomyces dermatitids. Blastomycosis is a pulmonary infection that can lead to fever, cough and (rarely) symptoms similar to tuberculosis. Hydroxystilbamidine has largely been replaced with amphotericin B. DB14754 Solriamfetol small molecule approved 178429-62-4 194.234 C10H14N2O2 Q01959#Sodium-dependent dopamine transporter@P23975#Sodium-dependent noradrenaline transporter Solriamfetol weakly binds to dopamine and norepinephrine transporters but not serotonin transportersLabel2. Solriamfetol does not bind to dopamine, serotonin, norepinephrine, GABA, adenosine, histamine, orexin, benzodiazepines, or muscarinic and nicotinic receptorsLabel. D0M3CV DB14763 Cycloguanil small molecule approved 516-21-2 251.715 C11H14ClN5 Not Available D0O9YG DB14783 Diroximel fumarate small molecule approved 1577222-14-0 255.226 C11H13NO6 Q9GZZ6#Neuronal acetylcholine receptor subunit alpha-10 Diroximel fumarate relieves the neurological symptoms of relapsing MS with less gastrointestinal effects than its bioequivalent counterpart, dimethyl fumarate.2,7 It is important to note that diroximel fumarate can cause angioedema, anaphylaxis, hepatotoxicity, flushing, lymphopenia, and Progressive Multifocal Leukoencephalopathy (PML).7 DB14840 Ripretinib small molecule approved 1442472-39-0 510.367 C24H21BrFN5O2 P10721#Mast/stem cell growth factor receptor Kit@P09619#Platelet-derived growth factor receptor beta@Q02763#Angiopoietin-1 receptor@P35968#Vascular endothelial growth factor receptor 2@P15056#Serine/threonine-protein kinase B-raf@P16234#Platelet-derived growth factor receptor alpha As a broad-spectrum kinase inhibitor, ripretinib inhibits various gene mutations, increasing progression-free survival in patients with advanced gastrointestinal stromal tumors (GIST).10,11 It is effective in treating mutations that are resistant to chemotherapy with other kinase inhibitors, such as imatinib.7 D09AAK DB14879 Cefiderocol small molecule approved 1225208-94-5 752.21 C30H34ClN7O10S2 A0A0E1R3H3#Penicillin-binding protein 3@P02919#Penicillin-binding protein 1B@D6R448#Penicillin-binding protein 2 Similarly to other cephalosporins, cefiderocol exerts bactericidal activity against a range of bacterial species.Label,2 Cefiderocol has primarily shown efficacy against aerobic Gram negative bacteria including Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.2 D0Q7MA DB14914 Flortaucipir F-18 small molecule approved 1522051-90-6 262.278 C16H10FN3 P27338#Amine oxidase [flavin-containing] B@P21397#Amine oxidase [flavin-containing] A@P10636#Microtubule-associated protein tau DB14975 Voxelotor small molecule approved 1446321-46-5 337.379 C19H19N3O3 P69905#Hemoglobin subunit alpha Voxelotor modifies hemoglobin to prevent painful and dangerous sickle cell crises that normally lead to organ damage, hospitalization, and sometimes death.7 It prevents low hemoglobin, which is normally associated with the destruction of sickled blood cells in sickle cell disease. Voxelotor has led to up to a 40% increase in hemoglobin in clinical trials.1,2 D09RII DB15035 Zanubrutinib small molecule approved 1691249-45-2 471.561 C27H29N5O3 Q06187#Tyrosine-protein kinase BTK D0UT4W DB15091 Upadacitinib small molecule approved 1310726-60-3 380.375 C17H19F3N6O P23458#Tyrosine-protein kinase JAK1 Upadacitinib is a DMARD that works by inhibiting the Janus Kinases (JAKs), which are essential downstream cell signalling mediators of pro-inflammatory cytokines. It is believed that these pro-inflammatory cytokines play a role in many autoimmune inflammatory conditions, such as rheumatoid arthritis.6 In clinical trials, upadacitinib decreased the activity of pro-inflammatory interleukins, transiently increased the levels of lymphocytes, and insignificantly decreased the levels of immunoglobulins from the baseline.9 D07JAG DB15102 Pemigatinib small molecule approved 1513857-77-6 487.508 C24H27F2N5O4 P21802#Fibroblast growth factor receptor 2@P22455#Fibroblast growth factor receptor 4@P11362#Fibroblast growth factor receptor 1@P22607#Fibroblast growth factor receptor 3 D0O6UY DB01345 Potassium cation small molecule approved 24203-36-9 39.0983 K P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Not Available DB01346 Quinidine barbiturate small molecule approved 556.652 C32H36N4O5 P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P47869#Gamma-aminobutyric acid receptor subunit alpha-2@Q14524#Sodium channel protein type 5 subunit alpha@O00180#Potassium channel subfamily K member 1@P42262#Glutamate receptor 2 Not Available DB01348 Spirapril small molecule approved 83647-97-6 466.614 C22H30N2O5S2 P12821#Angiotensin-converting enzyme Spirapril is an angiotensin-converting enzyme (ACE) inhibitor. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. By blocking ACE, spirapril decreases angiotensin II which is a vasoconstrictor and inducer of aldosterone. So by inhibiting the enzymes, aldosterone secreation is decreased (so less sodium is reabsorbed) and there is a decrease in vasoconstriction. Combined, this leades to a decrease in blood pressure. D05MFG DB01351 Amobarbital small molecule approved 57-43-2 226.2722 C11H18N2O3 P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P47869#Gamma-aminobutyric acid receptor subunit alpha-2@P34903#Gamma-aminobutyric acid receptor subunit alpha-3@P48169#Gamma-aminobutyric acid receptor subunit alpha-4@P31644#Gamma-aminobutyric acid receptor subunit alpha-5@Q16445#Gamma-aminobutyric acid receptor subunit alpha-6@P43681#Neuronal acetylcholine receptor subunit alpha-4@P36544#Neuronal acetylcholine receptor subunit alpha-7@P42262#Glutamate receptor 2@Q13002#Glutamate receptor ionotropic, kainate 2 Not Available D0R6BR DB01353 Butobarbital small molecule approved 77-28-1 212.2456 C10H16N2O3 P47869#Gamma-aminobutyric acid receptor subunit alpha-2@P34903#Gamma-aminobutyric acid receptor subunit alpha-3@P48169#Gamma-aminobutyric acid receptor subunit alpha-4@P31644#Gamma-aminobutyric acid receptor subunit alpha-5@Q16445#Gamma-aminobutyric acid receptor subunit alpha-6@P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P43681#Neuronal acetylcholine receptor subunit alpha-4@P36544#Neuronal acetylcholine receptor subunit alpha-7@P42262#Glutamate receptor 2@Q13002#Glutamate receptor ionotropic, kainate 2 Butethal (also known as butobarbitone and butobarbital) belongs to a group of medicines called the barbiturates. It is thought to act on receptors in the brain (GABA receptors) causing the release of the chemical GABA. This chemical inhibits certain areas of the brain resulting in sleepiness. DB01357 Mestranol small molecule approved 72-33-3 310.4299 C21H26O2 P03372#Estrogen receptor Not Available D0J1ML DB01359 Penbutolol small molecule approved 38363-40-5 291.4284 C18H29NO2 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P28222#5-hydroxytryptamine receptor 1B D0W8SB DB01362 Iohexol small molecule approved 66108-95-0 821.1379 C19H26I3N3O9 Iohexol is an effective non-ionic, water-soluble contrast agent which is used in myelography, arthrography, nephroangiography, arteriography, and other radiographic procedures. Its low systemic toxicity is the combined result of low chemotoxicity and low osmolality. DB01364 Ephedrine small molecule approved 299-42-3 165.2322 C10H15NO P35348#Alpha-1A adrenergic receptor@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P23975#Sodium-dependent noradrenaline transporter Ephedrine is a sympathomimetic amine that activates adrenergic receptors, increasing heart rate and blood pressure, and causing bronchodilation.4 The therapeutic window is wide as patients can be given doses of 5mg up to 50mg.11 Patients should be counselled regarding the pressor effects of sympathomimetic amines and the risk of tachyphylaxis.4 D0LG8E DB01365 Mephentermine small molecule approved 100-92-5 163.2594 C11H17N P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Mephentermine is a sympathomimetic agent with mainly indirect effects on adrenergic receptors. It is used to maintain blood pressure in hypotensive states, for example, following spinal anesthesia. Although the central stimulant effects of mephentermine are much less than those of amphetamine, its use may lead to amphetamine-type dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1248) D0G1OZ DB01366 Procaterol small molecule approved 72332-33-3 290.3575 C16H22N2O3 P07550#Beta-2 adrenergic receptor Procaterol is a long-acting beta-2-adrenergic receptor agonist. It is a potent bronchodilator that may be administered orally or by aerosol inhalation. D0Z1WA DB01367 Rasagiline small molecule approved 136236-51-6 171.2383 C12H13N P27338#Amine oxidase [flavin-containing] B@P10415#Apoptosis regulator Bcl-2 Rasagiline is a propargylamine and an irreversible inhibitor of monoamine oxidase (MAO). MAO, a flavin-containing enzyme, regulates the metabolic degradation of catecholamines and serotonin in the CNS and peripheral tissues. It is classified into two major molecular species, A and B, and is localized in mitochondrial membranes throughout the body in nerve terminals, brain, liver and intestinal mucosa. MAO-A is found predominantly in the GI tract and liver, and regulates the metabolic degradation of circulating catecholamines and dietary amines. MAO-B is the major form in the human brain and is responsible for the regulation of the metabolic degradation of dopamine and phenylethylamine. In ex vivo animal studies in brain, liver and intestinal tissues rasagiline was shown to be a potent,selective, and irreversible monoamine oxidase type B (MAO-B) inhibitor. At the recommended therapeutic doses, Rasagiline was also shown to be a potent and irreversible inhibitor of MAO-B in platelets. The selectivity of rasagiline for inhibiting only MAO-B (and not MAO-A) in humans and the sensitivity to tyramine during rasagiline treatment at any dose has not been sufficiently characterized to avoid restriction of dietary tyramine and amines contained in medications. D06OMW DB01369 Quinupristin small molecule approved 120138-50-3 1022.23 C53H67N9O10S P0A7J6#50S ribosomal protein L10@P61182#50S ribosomal protein L22 Quinupristin is a streptogramin antibiotic, derived from pristinamycin I. By inhibiting the bacterial ribosomal subunits, protein synthesis is inhibited thus leading to eventual bacterial cell death or stasis. D0E2OU DB01370 Aluminium small molecule approved 7429-90-5 26.9815 Al P06870#Kallikrein-1@P05067#Amyloid beta A4 protein@P02787#Serotransferrin@P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Not Available D0V8TQ DB01377 Magnesium oxide small molecule approved 1309-48-4 40.304 MgO Not Available DB01378 Magnesium cation small molecule approved 22537-22-0 24.305 Mg P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Not Available DB01380 Cortisone acetate small molecule approved 50-04-4 402.4807 C23H30O6 P04150#Glucocorticoid receptor@P04083#Annexin A1 Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.3 The duration of action is moderate as it is generally given once daily.8 Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.3 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.3 DB01382 Glymidine small molecule approved 339-44-6 309.341 C13H15N3O4S P48048#ATP-sensitive inward rectifier potassium channel 1@Q09428#ATP-binding cassette sub-family C member 8 Glycodiazine is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin. DB01390 Sodium bicarbonate small molecule approved 144-55-8 84.0066 CHNaO3 Intravenous sodium bicarbonate therapy increases plasma bicarbonate, buffers excess hydrogen ion concentration, raises blood pH and reverses the clinical manifestations of acidosis. D02FLB DB01392 Yohimbine small molecule approved 146-48-5 354.4427 C21H26N2O3 P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P18825#Alpha-2C adrenergic receptor@P08908#5-hydroxytryptamine receptor 1A@P28222#5-hydroxytryptamine receptor 1B@P28221#5-hydroxytryptamine receptor 1D@P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P41595#5-hydroxytryptamine receptor 2B Yohimbine is an indolalkylamine alkaloid with chemical similarity to reserpine. Yohimbine blocks presynaptic alpha-2 adrenergic receptors. Its action on peripheral blood vessels resembles that of reserpine, though it is weaker and of short duration. Yohimbine's peripheral autonomic nervous system effect is to increase parasympathetic (cholinergic) and decrease sympathetic (adrenergic) activity. It is to be noted that in male sexual performance, erection is linked to cholinergic activity and to alpha-2 adrenergic blockade which may theoretically result in increased penile inflow, decreased penile outflow or both. Yohimbine exerts a stimulating action on the mood and may increase anxiety. Such actions have not been adequately studied or related to dosage although they appear to require high doses of the drug. Yohimbine has a mild anti-diuretic action, probably via stimulation of hypothalmic center and release of posterior pituitary hormone. Reportedly Yohimbine exerts no significant influence on cardiac stimulation and other effects mediated by (beta)-adrenergic receptors. Its effect on blood pressure, if any, would be to lower it; however, no adequate studies are at hand to quantitate this effect in terms of Yohimbine dosage. D0H4JM DB01393 Bezafibrate small molecule approved 41859-67-0 361.819 C19H20ClNO4 Q03181#Peroxisome proliferator-activated receptor delta@P37231#Peroxisome proliferator-activated receptor gamma@Q07869#Peroxisome proliferator-activated receptor alpha@O75469#Nuclear receptor subfamily 1 group I member 2@P19793#Retinoic acid receptor RXR-alpha@P28702#Retinoic acid receptor RXR-beta@P48443#Retinoic acid receptor RXR-gamma Bezafibrate is an antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. Bezafibrate lowers elevated blood lipids (triglycerides and cholesterol). Elevated VLDL and LDL are reduced by treatment with bezafibrate, whilst HDL-levels are increased. The activity of triglyceride lipases (lipoprotein lipase and hepatic lipoproteinlipase) involved in the catabolism of triglyceride-rich lipoproteins is increased by bezafibrate. In the course of the intensified degradation of triglyceride-rich lipoproteins (chylomicrons, VLDL) precursors for the formation of HDL are formed which explains an increase in HDL. Furthermore, cholesterol biosynthesis is reduced by bezafibrate, which is accompanied by a stimulation of the LDL-receptor-mediated lipoprotein catabolism. Elevated fibrinogen appears to be an important risk-factor, alongside the lipids, smoking and hypertension, in the development of atheroma. Fibrinogen plays an important role in viscosity, and therefore blood flow, and also appears to play an important role in thrombus development and lysability. Bezafibrate exerts an effect on thrombogenic factors. A significant decrease in elevated plasma fibrinogen levels can be achieved. This may lead, amongst other things, to a reduction in both blood and plasma viscosity. Inhibition of platelet aggregation has also been observed. A reduction in blood glucose concentration due to an increase in glucose tolerance has been reported in diabetic patients. In the same patients, the concentration of fasting and postprandial free fatty acids was reduced by bezafibrate. D00WCX DB01394 Colchicine small molecule approved 64-86-8 399.437 C22H25NO6 Q7KQL5#Tubulin beta chain Colchicine reduces the pain resulting from gout and reduces flares of Familial Mediterranean fever by interfering with inflammatory pathways.2,13 This drug has a narrow therapeutic index.12 D09DHY DB01395 Drospirenone small molecule approved 67392-87-4 366.4932 C24H30O3 P08235#Mineralocorticoid receptor@P10275#Androgen receptor@P06401#Progesterone receptor@P04150#Glucocorticoid receptor Drospirenone inhibits the maturation of follicles and inhibits ovulation, preventing pregnancy. It has antiandrogen effects, improving acne and hirsutism. When combined with ethinyl estradiol, it has been shown to have favorable effects on the plasma lipid profile.20 Due to its similarity to naturally occurring progesterone, drospirenone is thought to be associated with a lower incidence of progesterone contraceptive related adverse effects, such as breast tenderness and mood swings.1 D0Z4ZT DB01396 Digitoxin small molecule approved 71-63-6 764.9391 C41H64O13 P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Digitoxin is a cardiac glycoside sometimes used in place of DIGOXIN. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting (From Martindale, The Extra Pharmacopoeia, 30th ed, p665). It is eliminated hepatically making it useful in patients with poor or erratic kidney function, although it is now rarely used in practice. Digitoxin lacks the strength of evidence that digoxin has in the management of heart failure. D0M3QP DB01399 Salsalate small molecule approved 552-94-3 258.2262 C14H10O5 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Salsalate is a nonsteroidal anti-inflammatory agent for oral administration. Salsalate's mode of action as an anti-inflammatory and antirheumatic agent may be due to inhibition of synthesis and release of prostaglandins. The usefulness of salicylic acid, the active in vivo product of salsalate, in the treatment of arthritic disorders has been established. In contrast to aspirin, salsalate causes no greater fecal gastrointestinal blood loss than placebo. D0Y0JH DB01400 Neostigmine small molecule approved 59-99-4 223.2915 C12H19N2O2 P22303#Acetylcholinesterase Neostigmine is a cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. By inhibiting acetylcholinesterase, more acetylcholine is available in the synapse, therefore, more of it can bind to the fewer receptors present in myasthenia gravis and can better trigger muscular contraction. D08USJ DB01401 Choline magnesium trisalicylate small molecule approved 64425-90-7 539.814 C26H29MgNO10 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Trisalicylate-choline is a non-steroidal anti-inflammatory drug (NSAID) that contains a combination of choline salicylate and magnesium salicylate. Does not affect platelet aggregation. D0I2VR DB01403 Methotrimeprazine small molecule approved 60-99-1 328.472 C19H24N2OS P21728#D(1A) dopamine receptor@P20309#Muscarinic acetylcholine receptor M3@P08913#Alpha-2A adrenergic receptor@P35367#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor Methotrimeprazine is a phenothiazine with pharmacological activity similar to that of both chlorpromazine and promethazine. It has the histamine-antagonist properties of the antihistamines together with central nervous system effects resembling those of chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604) DB01406 Danazol small molecule approved 17230-88-5 337.4553 C22H27NO2 P10275#Androgen receptor@P06401#Progesterone receptor@P30968#Gonadotropin-releasing hormone receptor@Q96P88#Putative gonadotropin-releasing hormone II receptor@P13500#C-C motif chemokine 2 Danazol is a derivative of the synthetic steroid ethisterone, a modified testosterone. It was approved by the U.S. Food and Drug Administration (FDA) as the first drug to specifically treat endometriosis, but its role as a treatment for endometriosis has been largely replaced by the gonadotropin-releasing hormone (GnRH) agonists. Danazol has antigonadotropic and anti-estrogenic activities. Danazol acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. D09IPV DB01407 Clenbuterol small molecule approved 37148-27-9 277.19 C12H18Cl2N2O P07550#Beta-2 adrenergic receptor@P08588#Beta-1 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P01138#Beta-nerve growth factor@P01375#Tumor necrosis factor Clenbuterol is a substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma. Although approved for use in some countries, as of fall, 2006, clenbuterol is not an ingredient of any therapeutic drug approved by the U.S. Food and Drug Administration. D0X5NX DB01409 Tiotropium small molecule approved 186691-13-4 392.512 C19H22NO4S2 P20309#Muscarinic acetylcholine receptor M3@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5 Tiotropium is a long acting antimuscarinic that causes bronchodilation.1,2,3,4,5 The effects of tiotropium last over 24 hours and there is a wide therapeutic index as overdoses are uncommon even at doses well above the recommended maximum.2,3,4,5 D0P1WA DB01410 Ciclesonide small molecule approved 126544-47-6 540.697 C32H44O7 P04150#Glucocorticoid receptor Ciclesonide is a pro-drug that is enzymatically hydrolyzed to a pharmacologically active metabolite, C21-desisobutyryl-ciclesonide (des-ciclesonide or RM1) following intranasal application. Des-ciclesonide has anti-inflammatory activity with affinity for the glucocorticoid receptor that is 120 times higher than the parent compound. The precise mechanism through which ciclesonide affects allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic inflammation. D0K7HU DB01413 Cefepime small molecule approved 88040-23-7 480.561 C19H24N6O5S2 P02919#Penicillin-binding protein 1B@A0A0E1R3H3#Penicillin-binding protein 3@D6R448#Penicillin-binding protein 2 Cefepime is a fourth-generation cephalosporin antibiotic.5,6 It is active against Gram-negative bacteria such as Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa, and Gram-positive bacteria such as Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pneumoniae, Streptococcus pyogenes and Viridans group streptococci.5,6 Compared to third-generation cephalosporins, cefepime has an extended Gram-negative coverage. Whereas other cephalosporins are degraded by plasmid- and chromosome-mediated beta-lactamases, cefepime is stable and not significantly hydrolyzed by these enzymes.1,4 Cefepime is also a poor inducer of type 1 beta-lactamases and, therefore, a good alternative against bacteria resistant to third-generation cephalosporins.1 D0A1CB DB01415 Ceftibuten small molecule approved 97519-39-6 410.425 C15H14N4O6S2 P02919#Penicillin-binding protein 1B Ceftibuten is an antibiotic with bactericidal actions. D05JDR DB01416 Cefpodoxime small molecule approved 80210-62-4 427.455 C15H17N5O6S2 Cefpodoxime is shown to be effective against most Gram positive and Gram negative bacteria, except Pseudomonas aeruginosa, Enterococcus, and Bacteroides fragilis. D0W6CA DB01418 Acenocoumarol small molecule approved 152-72-7 353.3255 C19H15NO6 Q9BQB6#Vitamin K epoxide reductase complex subunit 1 Acenocoumarol inhibits the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of certain glutamic acid residues near the N-terminals of clotting factors II, VII, IX and X, the vitamin K-dependent clotting factors. Glutamic acid carboxylation is important for the interaction between these clotting factors and calcium. Without this interaction, clotting cannot occur. Both the extrinsic (via factors VII, X and II) and intrinsic (via factors IX, X and II) are affected by acenocoumarol. D05HFY DB01419 Antrafenine small molecule approved 55300-29-3 588.5435 C30H26F6N4O2 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Its mode of action is not fully understood; however, its ability to inhibit prostaglandin synthesis may be involved in the anti-inflammatory effect. DB01420 Testosterone propionate small molecule approved 57-85-2 344.4877 C22H32O3 P10275#Androgen receptor The administration of testosterone propionate can induce production of proteins related to male sexual development.5 Clinical trials have shown a decrease in plasma LH after the administration of testosterone propionate.1 DB01421 Paromomycin small molecule approved 7542-37-2 615.6285 C23H45N5O14 Q5SHN7#30S ribosomal protein S10 Paromomycin is a broad spectrum aminoglycoside antibiotic produced by Streptomyces rimosus var. paromomycinus. The in vitro and in vivo antibacterial action of paromomycin closely parallels that of neomycin. D04NDM DB01424 Aminophenazone small molecule approved 58-15-1 231.2936 C13H17N3O Aminophenazone exhibits analgesic, anti-inflammatory, and antipyretic properties. DB01426 Ajmaline small molecule approved 4360-12-7 326.4326 C20H26N2O2 Q14524#Sodium channel protein type 5 subunit alpha Ajmaline is a class 1A antiarrhythmic agent. By interfering with the sodium channels, this drug allows for improvement in abnormal rhythms of the heart D02GUG DB01427 Amrinone small molecule approved 60719-84-8 187.198 C10H9N3O Q14432#cGMP-inhibited 3',5'-cyclic phosphodiesterase A@P01375#Tumor necrosis factor@Q13370#cGMP-inhibited 3',5'-cyclic phosphodiesterase B@P27815#cAMP-specific 3',5'-cyclic phosphodiesterase 4A@Q07343#cAMP-specific 3',5'-cyclic phosphodiesterase 4B@Q08493#cAMP-specific 3',5'-cyclic phosphodiesterase 4C@Q08499#cAMP-specific 3',5'-cyclic phosphodiesterase 4D Amrinone is a positive inotropic cardiotonic with vasodilator properties, phosphodiesterase inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell. DB01428 Oxybenzone small molecule approved 131-57-7 228.2433 C14H12O3 P03372#Estrogen receptor@P10275#Androgen receptor@P06401#Progesterone receptor@Q92731#Estrogen receptor beta Oxybenzone is an organic compound used in sunscreens. It is a derivative of benzophenone. DB01430 Almitrine small molecule approved 27469-53-0 477.5522 C26H29F2N7 P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Almitrine is a respiratory stimulant that enhances respiration by acting as an agonist of peripheral chemoreceptors located on the carotid bodies. D0D9NA DB01435 Antipyrine small molecule approved 60-80-0 188.2258 C11H12N2O P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Antipyrine is an analgesic and antipyretic that has been given by mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver. (From Martindale, The Extra Pharmacopoeia, 30th ed, p29) DB01436 Alfacalcidol small molecule approved 41294-56-8 400.6371 C27H44O2 P11473#Vitamin D3 receptor@O15528#25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial@P19793#Retinoic acid receptor RXR-alpha Alfacalcidol works to increase serum levels of calcium by stimulating intestinal calcium absorption, reabsorption of calcium from bone, and possibly the renal reabsorption of calcium. It also modestly promotes intestinal phosphorus absorption.9 In patients with renal failure, alfacalcidol increased intestinal calcium and phosphorus absorption in a dose-related manner. This increase in calcium and phosphorus levels occurs within three days following drug administration: this effect was reversed within three days of drug discontinuation. In patients with chronic renal failure, serum calcium levels were elevated while parathyroid hormone and alkaline phosphatase levels returned to normal levels within five days following alfacalcidol administration.12 Since alfacalcidol suppresses parathyroid hormone, a reduction in parathyroid hormone levels is achieved more rapidly in patients on intermittent intravenous therapy, with significant reductions occurring within three months of therapy. In patients receiving daily oral therapy of alfacalcidol, the time it takes alfacalcidol to normalize plasma calcium levels may be up to several months, possibly reflecting calcium being utilized for bone mineralization.9 In patients with nutritional osteomalacia, alfacalcidol increased calcium absorption with six hours of oral administration and the effects peaked at 24 hours.12 DB01437 Glutethimide small molecule approved 77-21-4 217.2637 C13H15NO2 P14867#Gamma-aminobutyric acid receptor subunit alpha-1 Glutethimide, like the barbiturates, is a hypnotic sedative. It was introduced in 1954 as a safer alternative to barbiturates but was soon determined to be just as likely to cause addiction and withdrawal symptoms. D0Z9NZ DB01438 Phenazopyridine small molecule approved 94-78-0 213.2385 C11H11N5 P35498#Sodium channel protein type 1 subunit alpha Phenazopyridine acts as a local anesthetic offering relief from irritating conditions of the urinary tract. It relieves urinary urgency frequency, burning, pain, and discomfort.14,18 D00VUL DB01440 gamma-Hydroxybutyric acid small molecule approved 591-81-1 104.1045 C4H8O3 P18505#Gamma-aminobutyric acid receptor subunit beta-1 GHB predominantly works at two distinct binding sites in the central nervous system: it works as an agonist at the newly-characterized excitatory GHB receptor, while acting as a weak agonist at the inhibitory GABAB receptor. Since it is a naturally occurring substance, its physiological action is similar to that of some endogenous neurotransmitters in mammalian brain. GHB is probably synthesized from GABA in GABAergic neurons, and released when the neurons fire. DB01452 Diamorphine small molecule approved 561-27-3 369.411 C21H23NO5 P35372#Mu-type opioid receptor@P41145#Kappa-type opioid receptor@P41143#Delta-type opioid receptor@P23141#Liver carboxylesterase 1 The onset of heroin's effects is dependent on the method of administration. Taken orally, heroin is totally metabolized in vivo via extensive first-pass metabolism into morphine before crossing the blood-brain barrier; so the effects are the same as orally administered morphine 5,6. Take by injection, diamorphine's acetyl groups facilitate rapid crossing into the brain 5,6. Once in the brain, heroin is rapidly metabolized into morphine by removal of the acetyl groups, therefore making it a prodrug for the delivery of morphine 5,6. Subsequently, whether eliciting actions peripherally (on smooth muscle, skeletal muscle, kidney, lung, liver, or spleen tissue 5, for example) or on the central nervous system, it is ultimately the morphine metabolite of heroin that then binds with opioid receptors and produces the narcotic opioid effects commonly associated with the substance 5,6. DB15233 Avapritinib small molecule approved 1703793-34-3 498.57 C26H27FN10 P10721#Mast/stem cell growth factor receptor Kit Avapritinib is a selective kinase inhibitor that negatively modulates the action of cell transporters to resensitize them to other chemotherapies.4 It has a long duration of action as it is given once daily.4 Patients should be counselled regarding the risk of intracranial hemorrhage, CNS effects, and embryo-fetal toxicity.4 D0UO2P DB15328 Ubrogepant small molecule approved 1374248-77-7 549.554 C29H26F3N5O3 Q16602#Calcitonin gene-related peptide type 1 receptor Ubrogepant acutely treats migraine headache pain by blocking the activity of a key transmitter involved in migraine pathogenesis.5 Exposure to ubrogepant can be significantly increased in patients with severe hepatic or renal insufficiency - dose adjustments are required for these patients in order to avoid excessive exposure, and ubrogepant is not recommended in patients with end-stage renal disease.5 D07GXR DB15444 Elexacaftor small molecule approved 2216712-66-0 597.66 C26H34F3N7O4S P13569#Cystic fibrosis transmembrane conductance regulator As a CFTR corrector, elexacaftor works to increase the amount of mature CFTR proteins present on the surface of cells.6 When used in combination with CFTR potentiators, which enhance the function of cell-surface CFTR proteins, drugs like elexacaftor help to improve a variety of multi-organ cystic fibrosis symptoms, including lung function, nutritional status, and overall quality of life.3 TrikaftaTM, the triple combination product containing elexacaftor, may cause elevations in liver transaminases. Liver function testing should be conducted prior to beginning Trikafta, every 3 months for the first year of treatment, and annually thereafter.6 DB15465 Benzhydrocodone small molecule approved 1259440-61-3 403.478 C25H25NO4 Benzhydrocodone is rapidly metabolized to hydrocodone which acts on the central nervous system to produce analgesia. The action of hydrocodone in the brain can also produce euphoria, leading to addiction. DB15467 Cinoxate small molecule approved 104-28-9 250.294 C14H18O4 Not Available DB15477 Alloin small molecule approved 8015-61-0 418.398 C21H22O9 Not Available DB15479 Zirconium chloride hydroxide small molecule approved 10119-31-0 143.68 ClHOZr Not Available DB15480 Resorcinol monoacetate small molecule approved 102-29-4 152.149 C8H8O3 Not Available DB15494 Edotreotide gallium Ga-68 small molecule approved 1486.55 C65H89GaN14O18S2 P30874#Somatostatin receptor type 2@P35346#Somatostatin receptor type 5@P32745#Somatostatin receptor type 3@P30872#Somatostatin receptor type 1 Edotreotide gallium Ga-68 binds to somatostatin receptors where it emits beta particle radiation for detection by positron emission tomography.7 The duration of action is short as it has short radioactive and biological half lives.4,8 Patients should hydrate before and after the administration of this medication to encourage frequent urination and rapid clearance.7 DB15534 Colchiceine small molecule approved 477-27-0 385.416 C21H23NO6 Q7KQL5#Tubulin beta chain@Q71U36#Tubulin alpha-1A chain Not Available DB15566 Prednisolone acetate small molecule approved 52-21-1 402.4807 C23H30O6 P04150#Glucocorticoid receptor Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.4 Prednisolone acetate has a short duration of action as the half life is 2-3 hours.5 Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces.4 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.4 DB15576 Ethyl salicylate small molecule approved 118-61-6 166.1739 C9H10O3 Not Available DB15594 Brilliant blue G small molecule approved 6104-58-1 854.02 C47H48N3NaO7S2 Brilliant Blue G aids in ophthalmologic surgery by rendering it easier to identify the internal limiting membrane (ILM) for surgical removal.8 DB15598 Ferric maltol small molecule approved 33725-54-1 431.154 C18H15FeO9 P05106#Integrin beta-3@P49281#Natural resistance-associated macrophage protein 2 Ferric maltol is used to provide supplemental iron to patients with an iron deficiency.7 It has a wide therapeutic index as patients generally take 30mg twice daily, while concentrations of 20mg/kg may produce toxicity.7 Patients should be counselled regarding the risk of inflammatory bowel disease flares, iron overload, and accidental ingestion in children.7 D02EXZ DB15617 Ferric derisomaltose small molecule approved 1345510-43-1 562.297 C18H34FeO16 P69905#Hemoglobin subunit alpha@P02786#Transferrin receptor protein 1 Ferric derisomaltase increases the reticulocyte count and ultimately increases hemoglobin, treating iron deficiency anemia and its various symptoms.5,3 Parenteral iron, such as ferric derisomaltose, may cause false elevations in serum bilirubin levels and falsely reduced serum calcium.10,11 DB15678 Calcium undecylenate small molecule approved 1322-14-1 406.62 C22H38CaO4 Not Available DB15679 Aluminum subacetate small molecule approved 142-03-0 162.0769 C4H7AlO5 Not Available DB15685 Selpercatinib small molecule approved 2152628-33-4 525.613 C29H31N7O3 P35916#Vascular endothelial growth factor receptor 3@P17948#Vascular endothelial growth factor receptor 1@P21802#Fibroblast growth factor receptor 2@P11362#Fibroblast growth factor receptor 1@P22607#Fibroblast growth factor receptor 3@P07949#Proto-oncogene tyrosine-protein kinase receptor Ret D01KOA DB01495 Dichloralphenazone small molecule approved 480-30-8 519.032 C15H18Cl6N2O5 Not Available DB01501 Difenoxin small molecule approved 28782-42-5 424.5341 C28H28N2O2 Difenoxin acts as a potent antidiarrheal by slowing the movement of the intestines. It also crosses the blood brain barrier to a slight degree to exert weak sedative and analgesic effects. DB01544 Flunitrazepam small molecule approved 1622-62-4 313.2832 C16H12FN3O3 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Flunitrazepam is a powerful hypnotic drug that is a benzodiazepine derivative. It has powerful hypnotic, sedative, anxiolytic, and skeletal muscle relaxant properties. The drug is sometimes used as a date rape drug. In the United States, the drug has not been approved by the Food and Drug Administration for medical use, and is considered to be an illegal drug. It has however been approved in the United Kingdom and other countries. D0W2NM DB01551 Dihydrocodeine small molecule approved 125-28-0 301.3801 C18H23NO3 Possible opioid related side effects include, but are not limited to, drowsiness, nausea, headache, dry mouth, constipation, difficulty passing urine, and mild euphoria. D0T6RC DB01558 Bromazepam small molecule approved 1812-30-2 316.153 C14H10BrN3O P28472#Gamma-aminobutyric acid receptor subunit beta-3 Bromazepam is a lipophilic, long-acting benzodiazepine and with sedative, hypnotic, anxiolytic and skeletal muscle relaxant properties. It does not possess any antidepressant qualities. Bromazepam, like other benzodiazepines, presents a risk of abuse, misuse, and dependence. According to many psychiatric experts, Bromazepam has a greater abuse potential than other benzodiazepines because of fast resorption and rapid onset of action. D0E3FD DB01559 Clotiazepam small molecule approved 33671-46-4 318.821 C16H15ClN2OS P28472#Gamma-aminobutyric acid receptor subunit beta-3 Clotiazepam is a thienodiazepine possessing anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It increases the stage 2 non-rapid eye movement sleep. D0R4DP DB01563 Chloral hydrate small molecule approved 302-17-0 165.403 C2H3Cl3O2 Not Available D02OAV DB01574 Attapulgite small molecule approved 12174-11-7 412.684 AlH9MgO15Si4 Attapulgite is an adsorptive magnesium aluminium phyllosilicate which binds to toxins, bacteria and water. D0DF9Z DB01575 Kaolin small molecule approved 1332-58-7 258.156 Al2H4O9Si2 Kaolin is an adsorptive agent. DB01576 Dextroamphetamine small molecule approved 51-64-9 135.2062 C9H13N Q05940#Synaptic vesicular amine transporter@P23975#Sodium-dependent noradrenaline transporter@Q01959#Sodium-dependent dopamine transporter@Q96RJ0#Trace amine-associated receptor 1@P35368#Alpha-1B adrenergic receptor Dextroamphetamine is a noncatecholamine, sympathomimetic amine that acts as a CNS stimulant.Label Dextroamphetamine raises systolic and diastolic blood pressure, acts as a weak bronchodilator, and also acts as a respiratory stimulant.Label The general mechanism of action of dextroamphetamine has not been well established.Label D0T3LF DB01577 Metamfetamine small molecule approved 537-46-2 149.2328 C10H15N P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P27338#Amine oxidase [flavin-containing] B@P21397#Amine oxidase [flavin-containing] A Methamphetamine is a potent central nervous system stimulant which affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and responses associated with alertness or alarm conditions. The acute effects of the drug closely resemble the physiological and psychological effects of an epinephrine-provoked fight-or-flight response, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite. DB01579 Phendimetrazine small molecule approved 634-03-7 191.274 C12H17NO P35348#Alpha-1A adrenergic receptor@P23975#Sodium-dependent noradrenaline transporter@P35368#Alpha-1B adrenergic receptor Phendimetrazine is a phenylalkylamine sympathomimetic amine with pharmacological activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance has been demonstrated with all drugs of this class in which these phenomena have been looked for. Drugs of this class used in obesity are commonly known as ''anorectics or anorexigenics." It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions or metabolic effects, may be involved. D0T6SU DB01580 Oxprenolol small molecule approved 6452-71-7 265.348 C15H23NO3 P08588#Beta-1 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P07550#Beta-2 adrenergic receptor Oxprenolol is a non-selective beta blocker with some intrinsic sympathomimetic activity. Oxprenolol is a lipophilic molecule and hence, it is able to cross the blood-brain barrier. As such, it is associated with a higher incidence of CNS-related side effects than hydrophilic ligands such as atenolol, sotalol and nadolol. Oxprenolol is an potent beta-blocker and should not be administered to asthmatics because it can cause irreversible airway failure and inflammation. D0X2MB DB01581 Sulfamerazine small molecule approved 127-79-7 264.304 C11H12N4O2S P0AC13#Dihydropteroate synthase Sulfonamides act as competitive inhibitors of the enzyme dihydropteroate synthetase (DHPS), an enzyme involved in folate synthesis in bacteria. D0H1GJ DB01582 Sulfamethazine small molecule approved 57-68-1 278.33 C12H14N4O2S P0AC13#Dihydropteroate synthase Sulfamethazine is a sulfonamide drug that inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA) for binding to dihydropteroate synthetase (dihydrofolate synthetase). Sulfamethazine is bacteriostatic in nature. Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial nucleotides and DNA. D0V9YR DB01583 Liotrix small molecule approved 8065-29-0 1471.8072 C30H21I7N2Na2O8 P10827#Thyroid hormone receptor alpha@P10828#Thyroid hormone receptor beta Thyroid hormone drugs are natural or synthetic preparations containing T4 or T3 or both. T4 and T3 are produced in the human thyroid gland by the iodination and coupling of the amino acid tyrosine. Liotrix is a synthetic preparation of T4 and T3 in a 4:1 weight-based ratio. These hormones enhance oxygen consumption by most tissues of the body and increase the basal metabolic rate and the metabolism of carbohydrates, lipids and proteins. Thus, they exert a profound influence on every organ system in the body and are of particular importance in the development of the central nervous system. DB01586 Ursodeoxycholic acid small molecule approved 128-13-2 392.572 C24H40O4 P52895#Aldo-keto reductase family 1 member C2@Q96RI1#Bile acid receptor Ursodiol (commonly known as ursodeoxycholic acid) is a product of metabolism of bacteria in the intestine. It is considered a secondary bile acid. The other type of bile acid, primary bile acids, are produced hepatically and subsequently stored in the gallbladder. When primary bile acids are secreted into the large intestine, they can be broken down into secondary bile acids by bacteria present in the intestine. Both types of bile acids assist in the metabolism of dietary fat. Ursodeoxycholic acid regulates cholesterol levels by slowing the rate at which the intestine is able to absorb cholesterol and also acts to break down micelles, which contain cholesterol. Because of this property, ursodeoxycholic acid is used to treat gall stones non-surgically. D0G3SH DB01587 Ketazolam small molecule approved 27223-35-4 368.814 C20H17ClN2O3 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA), which results in sedative, hypnotic, anxiolytic, anticonvulsant, muscle relaxant and amnesic action. DB01588 Prazepam small molecule approved 2955-38-6 324.804 C19H17ClN2O P28472#Gamma-aminobutyric acid receptor subunit beta-3 Prazepam is a benzodiazepine derivative with anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant activity. Benzodiazepines may be habit-forming (causing mental or physical dependence), especially when taken for a long time or in high doses. D0G3AQ DB01589 Quazepam small molecule approved 36735-22-5 386.794 C17H11ClF4N2S P28472#Gamma-aminobutyric acid receptor subunit beta-3 Quazepam is a benzodiazepine derivative. The main pharmacological action of quazepam is the enhancement of the neurotransmitter GABA at the GABAA receptor. D03NPH DB01590 Everolimus small molecule approved 159351-69-6 958.24 C53H83NO14 P42345#Serine/threonine-protein kinase mTOR Not Available D0K3QS DB01591 Solifenacin small molecule approved 242478-37-1 362.473 C23H26N2O2 P20309#Muscarinic acetylcholine receptor M3@P08172#Muscarinic acetylcholine receptor M2@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5@P11229#Muscarinic acetylcholine receptor M1 Solifenacin antagonizes the M2 and M3 muscarinic receptors in the bladder to treat an overactive bladder.3,2 It has a long duration of action as it is usually taken once daily.3 Patients taking solifenacin should be aware of the risks of angioedema and anaphylaxis.3 D0L4YD DB01592 Iron small molecule approved 7439-89-6 55.845 Fe P06746#DNA polymerase beta@P69905#Hemoglobin subunit alpha@P02794#Ferritin heavy chain@P02787#Serotransferrin@P00450#Ceruloplasmin@Q9BY41#Histone deacetylase 8@Q9GZT9#Egl nine homolog 1@Q96FI4#Endonuclease 8-like 1@Q969S2#Endonuclease 8-like 2@P02786#Transferrin receptor protein 1 D0Y3TM DB01593 Zinc small molecule approved 7440-66-6 65.409 Zn P46663#B1 bradykinin receptor@P16455#Methylated-DNA--protein-cysteine methyltransferase@P04075#Fructose-bisphosphate aldolase A@P68104#Elongation factor 1-alpha 1@P06733#Alpha-enolase@O14556#Glyceraldehyde-3-phosphate dehydrogenase, testis-specific@P15531#Nucleoside diphosphate kinase A@C0H4Y6#Protein disulfide-isomerase@P30101#Protein disulfide-isomerase A3@Q06830#Peroxiredoxin-1 Zinc is involved in various aspects of cellular metabolism. It has been estimated that approximately 10% of human proteins may bind zinc, in addition to hundreds of proteins that transport and traffic zinc. It is required for the catalytic activity of more than 200 enzymes, and it plays a role in immune function wound healing, protein synthesis, DNA synthesis, and cell division. Zinc is an essential element for a proper sense of taste and smell and supports normal growth and development during pregnancy, childhood, and adolescence. It is thought to have antioxidant properties, which may be protective against accelerated aging and helps to speed up the healing process after an injury; however, studies differ as to its effectiveness. Zinc ions are effective antimicrobial agents even if administered in low concentrations 30. DB01595 Nitrazepam small molecule approved 146-22-5 281.2661 C15H11N3O3 P35498#Sodium channel protein type 1 subunit alpha Nitrazepam is a type of benzodiazepine drug. It is a powerful hypnotic drug which possesses strong sedative, anxiolytic, amnestic, anticonvulsant, and skeletal muscle relaxant properties. Nitrazepam shortens the time required to fall asleep and lengthens the duration of sleep. It is also useful for the management of myoclonic seizures. D0T5WK DB01597 Cilastatin small molecule approved 82009-34-5 358.453 C16H26N2O5S P16444#Dipeptidase 1 Cilastatin is a chemical compound which inhibits the human enzyme dehydropeptidase.6,5 Renal Dehydropeptidase degrades the antibiotic imipenem. Cilastatin is therefore combined intravenously with imipenem in order to protect it from dehydropeptidase and prolong its antibacterial effect. However, cilastatin in and of itself does not have any antibacterial activity. The increased renal excretion of unchanged imipenem appears to prevent proximal tubular necrosis associated with high doses of imipenem.2 D02GIU DB01598 Imipenem small molecule approved 64221-86-9 299.346 C12H17N3O4S P72355#Penicillin-binding protein 4@Q93LQ9#Beta-lactamase Imipenem is a beta-lactam antibiotic belongings to the subgroup of carbapenems.12,13 Imipenem is active against aerobic and anaerobic Gram positive as well as Gram negative bacteria including Pseudomonas aeruginosa and the Enterococcus. It exerts a bactericidal effects by disrupting cell wall synthesis. D0H3TD DB01599 Probucol small molecule approved 23288-49-5 516.842 C31H48O2S2 O95477#ATP-binding cassette sub-family A member 1@P23141#Liver carboxylesterase 1 Probucol lowers cholesterol levels by increasing LDL (low-density lipoprotein) breakdown. Additionally, probucol may inhibit cholesterol synthesis and delay cholesterol absorption. Probucol is a powerful antioxidant drug normally used to prevent vascular disease caused by the free radicals in the body. D0H2DQ DB01600 Tiaprofenic acid small molecule approved 33005-95-7 260.308 C14H12O3S P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Tiaprofenic acid is a non-steroidal anti-inflammatory drug of the arylpropionic acid (profen) class, used to treat pain, especially arthritic pain. The typical adult dose is 300mg twice daily. This drug is not recommended for use in the pediatric population. D0S7VO DB01601 Lopinavir small molecule approved 192725-17-0 628.8008 C37H48N4O5 Lopinavir inhibits the activity of an enzyme critical for the HIV viral lifecycle.7 It has a moderate duration of action necessitating once or twice daily dosing.7 Lopinavir, like other protease inhibitors, has a propensity for participating in drug interactions - use caution when administering lopinavir to patients maintained on other pharmaceutical agents as pharmacodynamic and pharmacokinetic interactions are common. Fatal hepatotoxicity and pancreatitis have been noted in patients undergoing therapy with lopinavir and patients with an increased baseline risk of these events should be monitored closely throughout therapy.7 D0U5GB DB01602 Bacampicillin small molecule approved 50972-17-3 465.52 C21H27N3O7S P0AEB2#D-alanyl-D-alanine carboxypeptidase DacA@P24228#D-alanyl-D-alanine carboxypeptidase DacB@P08506#D-alanyl-D-alanine carboxypeptidase DacC@P02919#Penicillin-binding protein 1B Bacampicillin is a prodrug of ampicillin and is microbiologically inactive. D04CFW DB01603 Meticillin small molecule approved 61-32-5 380.415 C17H20N2O6S P0A3M6#Penicillin-binding protein 2B@Q8DR59#Penicillin-binding protein 1A@Q7CRA4#Penicillin-binding protein 1b Meticillin (INN, BAN) or methicillin (USAN) is a narrow spectrum beta-lactam antibiotic of the penicillin class. It is no longer clinically used. Its role in therapy has been largely replaced by flucloxacillin and dicloxacillin, however the term methicillin-resistant Staphylococcus aureus (MRSA) continues to be used to describe Staphylococcus aureus strains resistant to all penicillins. D06TQZ DB01604 Pivampicillin small molecule approved 33817-20-8 463.547 C22H29N3O6S Pivampicillin is the pivaloyloxymethyl ester of (the semi-synthetic penicillin) ampicillin. It is an inactive pro-drug, which is converted during its absorption from the gastrointestinal tract to the microbiologically active ampicillin, together with formaldehyde and pivalic acid, by non-specific esterases present in most body tissues. Amounts in excess of 99% of the pivampicillin absorbed are converted to ampicillin within 15 minutes of absorption. D04KAQ DB01605 Pivmecillinam small molecule approved 32886-97-8 439.569 C21H33N3O5S Pivmecillinam is a pivaloyloxymethyl ester of amdinocillin that is well absorbed orally, but broken down to amdinocillin in the intestinal mucosa. It is active against gram-negative organisms and used as for amdinocillin. D08HDY DB01606 Tazobactam small molecule approved 89786-04-9 300.291 C10H12N4O5S P62593#Beta-lactamase TEM@P18251#Beta-lactamase Ohio-1@P0AD64#Beta-lactamase SHV-1 Tazobactam inhibits the action of bacterial beta-lactamase producing organisms, which are normally resistant to beta-lactam antibiotics. This augments the effects of antibiotics which would otherwise not be effective in treating certain infections. These antibiotics contain a beta-lactam ring in their chemical structure, which is destroyed by beta-lactam resistant organisms.4 When combined with other antibiotics, a variety of infections, including serious and life-threatening infections may be treated.14,11 D0QQ7D DB01607 Ticarcillin small molecule approved 34787-01-4 384.427 C15H16N2O6S2 D08USU DB01608 Periciazine small molecule approved 2622-26-6 365.492 C21H23N3OS P08913#Alpha-2A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P10275#Androgen receptor Pericyazine is a phenothiazine of the piperidine group. It has been shown to reduce pathologic arousal and affective tension in some psychotic patients, while the symptoms of abnormal mental integration are relatively unaffected. It is a sedative phenothiazine with weak antipsychotic properties. It also has adrenolytic, anticholinergic, metabolic and endocrine effects, and an action on the extrapyramidal system. DB01609 Deferasirox small molecule approved 201530-41-8 373.3615 C21H15N3O4 Deferasirox is an orally active chelator that is selective for iron (as Fe3+). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. Although deferasirox has very low affinity for zinc and copper there are variable decreases in the serum concentration of these trace metals after the administration of deferasirox. The clinical significance of these decreases is uncertain. DB01610 Valganciclovir small molecule approved 175865-60-8 354.3617 C14H22N6O5 Valganciclovir is an antiviral medication used to treat cytomegalovirus infections. As the L-valyl ester of ganciclovir, it is actually a prodrug for ganciclovir. After oral administration, it is rapidly converted to ganciclovir by intestinal and hepatic esterases. After this, it (being an analogue of guanosine) gets incorporated into DNA and thus cannot be properly read by DNA polymerase. This results in the termination of the elongation of viral DNA. D06GWF DB01611 Hydroxychloroquine small molecule approved 118-42-3 335.872 C18H26ClN3O Q9NYK1#Toll-like receptor 7@Q9NR96#Toll-like receptor 9@Q9BYF1#Angiotensin-converting enzyme 2 Hydroxychloroquine affects the function of lysozomes in humans as well as plasmodia.4 Altering the pH of the lysozomes reduces low affinity self antigen presentation in autoimmue diseases and interferes with the ability of plasmodia to proteolyse hemoglobin for their energy requirements.4 Hydroxychloroquine has a long duration of action as it may be taken on a weekly basis for some indications.13 Hydroxychloroquine may lead to severe hypoglycemia and so diabetic patients are advised to monitor their blood glucose levels.13 Hydroxychloroquine is not effective against malaria in areas where chloroquine resistance has been reported.13 D0OJ4L DB01612 Amyl Nitrite small molecule approved 8017-89-8 117.1463 C5H11NO2 P16066#Atrial natriuretic peptide receptor 1 Amyl nitrite, in common with other alkyl nitrites, is a potent vasodilator. It expands blood vessels, resulting in lowering of the blood pressure. Alkyl nitrite functions as a source of nitric oxide, which signals for relaxation of the involuntary muscles. Adverse effects are related to this pharmacological activity and include hypotension, headache, flushing of the face, tachycardia, dizziness, and relaxation of involuntary muscles, especially the blood vessel walls and the anal sphincter. DB01613 Erythrityl tetranitrate small molecule approved 7297-25-8 302.11 C4H6N4O12 P16066#Atrial natriuretic peptide receptor 1@P20594#Atrial natriuretic peptide receptor 2 Erythrityl Tetranitrate is a vasodilator with general properties similar to nitroglycerin. DB01616 Alverine small molecule approved 150-59-4 281.4351 C20H27N P08908#5-hydroxytryptamine receptor 1A Alverine is a smooth muscle relaxant. Smooth muscle is a type of muscle that is not under voluntary control; it is the muscle present in places such as the gut and uterus. Alverine acts directly on the muscle in the gut, causing it to relax. This prevents the muscle spasms which occur in the gut in conditions such as irritable bowel syndrome and diverticular disease. Diverticular disease is a condition in which small pouches form in the gut lining. These pouches can trap particles of food and become inflamed and painful. In irritable bowel syndrome the normal activity of the gut muscle is lost. The muscle spasms result in symptoms such as heartburn, abdominal pain and bloating, constipation or diarrhoea. By relaxing the gut muscle, alverine citrate relieves the symptoms of this condition. Alverine also relaxes the smooth muscle in the womb (uterus). It is therefore also used to treat painful menstruation, which is caused by muscle spasms in the uterus (dysmenorrhea). DB01618 Molindone small molecule approved 7416-34-4 276.374 C16H24N2O2 P08908#5-hydroxytryptamine receptor 1A@P28223#5-hydroxytryptamine receptor 2A@P11229#Muscarinic acetylcholine receptor M1 Molindone is a dihydroindolone compound which is not structurally related to the phenothiazines, the butyrophenones, or the thioxanthenes. Molindone has a pharmacological profile in laboratory animals which predominantly resembles that of major tranquilizers causing reduction of spontaneous locomotion and aggressiveness, suppression of a conditioned response and antagonism of the bizarre stereotyped behavior and hyperactivity induced by amphetamines. In addition, molindone antagonizes the depression caused by the tranquilizing agent tetrabenazine. D09TPF DB01619 Phenindamine small molecule approved 82-88-2 261.3609 C19H19N P70174#Histamine H1 receptor Phenindamine is an antihistamine. Phenindamine blocks the effects of the naturally occurring chemical histamine in your body. Allergies are caused by an excessive type 1 hypersensitivity response of the body to allergens, mediated by inappropriate histamine signalling. By inhibiting the binding of histamine, antihistamines decrease the normal histamine response from cells, consequently decreasing allergic symptoms. D06UDO DB01620 Pheniramine small molecule approved 86-21-5 240.3434 C16H20N2 Q9H3N8#Histamine H4 receptor@P70174#Histamine H1 receptor@Q14994#Nuclear receptor subfamily 1 group I member 3 Pheniramine acts as an antagonist to allergic symptoms stemming from inappropriate histamine release to reduce edema, itching, and redness. The same antihistamine effect also produces sedation by acting in the central nervous system.1,9 D04OBB DB01621 Pipotiazine small molecule approved 39860-99-6 475.667 C24H33N3O3S2 P28223#5-hydroxytryptamine receptor 2A@P08908#5-hydroxytryptamine receptor 1A Pipotiazine has actions similar to those of other phenothiazines. Among the different phenothiazine derivatives, it appears to be less sedating and to have a weak propensity for causing hypotension or potentiating the effects of CNS depressants and anesthetics. However, it produces a high incidence of extra pyramidal reactions. It reduces activity of dopamine receptors in the limbic system. Its 5-HT antagonism helps normalize dopamine activity in the cortical regions. D0Z6QG DB01623 Thiothixene small molecule approved 3313-26-6 443.625 C23H29N3O2S2 P21728#D(1A) dopamine receptor@P14416#D(2) dopamine receptor Thiothixene is an antipsychotic of the thioxanthene series. Navane possesses certain chemical and pharmacological similarities to the piperazine phenothiazines and differences from the aliphatic group of phenothiazines. Although widely used in the treatment of schizophrenia for several decades, thiothixene is seldom used today in favor of atypical antipsychotics such as risperidone. D0E0LQ DB01624 Zuclopenthixol small molecule approved 53772-83-1 400.965 C22H25ClN2OS P35348#Alpha-1A adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P28223#5-hydroxytryptamine receptor 2A@P70174#Histamine H1 receptor Zuclopenthixol is a thioxanthene with therapeutic actions similar to the phenothiazine antipsychotics. It is an antagonist at D1 and D2 dopamine receptors. D0I8LU DB01625 Isopropamide small molecule approved 7492-32-2 353.5209 C23H33N2O P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4 Isopropamide is a long-acting quaternary anticholinergic drug. It is used in the treatment of peptic ulcer and other gastrointestinal disorders marked by hyperacidity and hypermotility. DB01626 Pargyline small molecule approved 555-57-7 159.2276 C11H13N P27338#Amine oxidase [flavin-containing] B@P21397#Amine oxidase [flavin-containing] A Pargyline is a monoamine oxidase B (MAO-B) inhibitor with antihypertensive properties. Patients taking pargyline must avoid concurrent consumption of tyramine-containing foods such as bleu cheese and beer, as this can lead to a hypertensive crisis. D0R0UJ DB01627 Lincomycin small molecule approved 154-21-2 406.54 C18H34N2O6S Lincomycin is a lincosamide antibiotic derived as a natural fermentation product from Streptomyces lincolnensis. Like clindamycin, lincomycin is active against Gram-positive cocci and bacilli as well as Gram-negative cocci and some other organisms such as Haemophilus spp. It is also effective against anaerobic bacteria, though in this regard clindamycin is generally more potent.1,2 Prescribing information highlights that the range of clinically confirmed effectiveness is largely limited to Staphylococcus spp. and Streptococcus spp., with additional activity noted in vitro.10 D0Q0EX DB01628 Etoricoxib small molecule approved 202409-33-4 358.842 C18H15ClN2O2S P35354#Prostaglandin G/H synthase 2 Etoricoxib is a COX-2 selective inhibitor (approximately 106 times more selective for COX-2 inhibition over COX-1). D09MGR DB01632 5-O-phosphono-alpha-D-ribofuranosyl diphosphate small molecule approved 13270-65-0 390.0696 C5H13O14P3 Q27796#Hypoxanthine-guanine phosphoribosyltransferase@Q9NWZ5#Uridine-cytidine kinase-like 1@Q27796#Hypoxanthine-guanine phosphoribosyltransferase@P07741#Adenine phosphoribosyltransferase@Q8VP84#Anthranilate phosphoribosyltransferase Not Available DB01638 Sorbitol small molecule approved 50-70-4 182.1718 C6H14O6 Not Available D09MXS DB01656 Roflumilast small molecule approved 162401-32-3 403.207 C17H14Cl2F2N2O3 Q08499#cAMP-specific 3',5'-cyclic phosphodiesterase 4D@P27815#cAMP-specific 3',5'-cyclic phosphodiesterase 4A@Q07343#cAMP-specific 3',5'-cyclic phosphodiesterase 4B@Q08493#cAMP-specific 3',5'-cyclic phosphodiesterase 4C Roflumilast (and its active metabolite, roflumilast N-oxide) increases cyclic adenosine-3′, 5′-monophosphate (cAMP) in lung cells by inhibiting PDE4. Increased cAMP activates PKA, which inactivates transcription factors involved in inflammation. Romflumilast also decreases the amount of sputum neutrophils and eosinophils in COPD patients. D0R4UW DB01698 Rutin small molecule approved 153-18-4 610.5175 C27H30O16 P16152#Carbonyl reductase [NADPH] 1@P42330#Aldo-keto reductase family 1 member C3 Not Available D09ALJ DB01708 Prasterone small molecule approved 53-43-0 288.4244 C19H28O2 Q07869#Peroxisome proliferator-activated receptor alpha@P03372#Estrogen receptor@P10275#Androgen receptor@Q92731#Estrogen receptor beta@O75469#Nuclear receptor subfamily 1 group I member 2@Q14994#Nuclear receptor subfamily 1 group I member 3@P28472#Gamma-aminobutyric acid receptor subunit beta-3@Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B DHEA is naturally produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA. DHEA is increased by exercise and calorie restriction. Some theorize that the increase in endogenous DHEA brought about by calorie restriction is partially responsible for the longer life expectancy known to be associated with calorie restriction. D0K0EK DB01718 Cetrimonium small molecule approved 6899-10-1 284.5435 C19H42N P9WPB7#Cyclopropane mycolic acid synthase 1@Q79FX6#Cyclopropane mycolic acid synthase MmaA2 Not Available DB01744 Camphor small molecule approved 464-49-3 152.2334 C10H16O Q8NER1#Transient receptor potential cation channel subfamily V member 1@Q8NET8#Transient receptor potential cation channel subfamily V member 3@O75762#Transient receptor potential cation channel subfamily A member 1@Q7Z2W7#Transient receptor potential cation channel subfamily M member 8@P00183#Camphor 5-monooxygenase Not Available D0H1QY DB01764 Dalfopristin small molecule approved 112362-50-2 690.85 C34H50N4O9S P50870#Streptogramin A acetyltransferase Dalfopristin is a streptogramin antibiotic, derived from pristinamycin IIA. D05AFC DB01783 Pantothenic acid small molecule approved 79-83-4 219.235 C9H17NO5 P0A6I3#Pantothenate kinase Pantothenic acid is used in the synthesis of coenzyme A (CoA). CoA is thought to act as a carrier molecule, allowing the entry of acyl groups into cells. This is of critical importance as these acyl groups are used as substrates in the tricarboxylic acid cycle to generate energy and in the synthesis of fatty acids, cholesterol, and acetylcholine. Additionally, CoA is part of acyl carrier protein (ACP), which is required in the synthesis of fatty acids in addition to CoAs use as a substrate. D07SJT DB01839 Propylene glycol small molecule approved 57-55-6 76.0944 C3H8O2 Q8GEZ8#B12-independent glycerol dehydratase Not Available DB01914 D-glucose small molecule approved 50-99-7 180.1559 C6H12O6 Blood glucose is an obligatory energy source for humans involved in various cellular activities, and it also acts as a signaling molecule for diverse glucose-sensing molecules and proteins. Glucose undergoes oxidation into carbon dioxide, water, and yields energy molecules in the process of glycolysis and subsequent citric cycle and oxidative phosphorylation.6 Glucose is readily converted into fat in the body which can be used as a source of energy as required. Under a similar conversion into storage of energy, glucose is stored in the liver and muscles as glycogen.11 Glucose stores are mobilized in a regulated manner, depending on the tissues' metabolic demands. Oral glucose tablets or injections serve to increase the supply of glucose and oral glucose administration is more effective in stimulating insulin secretion because it stimulates the incretin hormones from the gut, which promotes insulin secretion.10 D0C1FY DB01956 Taurine small molecule approved 107-35-7 125.147 C2H7NO3S Q9UBS5#Gamma-aminobutyric acid type B receptor subunit 1@O75311#Glycine receptor subunit alpha-3@Q13224#Glutamate receptor ionotropic, NMDA 2B@P23415#Glycine receptor subunit alpha-1@P37610#Alpha-ketoglutarate-dependent taurine dioxygenase@P54965#Choloylglycine hydrolase@P28472#Gamma-aminobutyric acid receptor subunit beta-3 The diet supplements containing taurine are formulated as a well-tolerated nitrogen source for nutritional support. Administration of diet supplements regulates the level of plasma amino acid concentration, nitrogen balance, weight and serum protein concentration to reach normal values, thus improving the nutritional status.Label DB01987 Cocarboxylase small molecule approved 136-08-3 424.306 C12H18N4O7P2S P27696#Acetolactate synthase, catabolic@P0AFG8#Pyruvate dehydrogenase E1 component@P94692#Pyruvate synthase@P23234#Indole-3-pyruvate decarboxylase@Q9LCV9#N(2)-(2-carboxyethyl)arginine synthase@P27302#Transketolase 1 Not Available DB00211 Midodrine small molecule approved 42794-76-3 254.2823 C12H18N2O4 P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor Midodrine is a prodrug, i.e., the therapeutic effect of orally administered midodrine is due to the major metabolite desglymidodrine formed by deglycination of midodrine. Administration of midodrine results in a rise in standing, sitting, and supine systolic and diastolic blood pressure in patients with orthostatic hypotension of various etiologies. Standing systolic blood pressure is elevated by approximately 15 to 30 mmHg at 1 hour after a 10-mg dose of midodrine, with some effect persisting for 2 to 3 hours. Midodrine has no clinically significant effect on standing or supine pulse rates in patients with autonomic failure. D02XJY DB00213 Pantoprazole small molecule approved 102625-70-7 383.37 C16H15F2N3O4S P20648#Potassium-transporting ATPase alpha chain 1 This drug acts to decrease gastric acid secretion, which reduces stomach acidity. Pantoprazole administration leads to long-lasting inhibition of gastric acid secretion.16 D0T6XX DB00214 Torasemide small molecule approved 56211-40-6 348.42 C16H20N4O3S P55011#Solute carrier family 12 member 2@Q13621#Solute carrier family 12 member 1 It is widely known that administration of torasemide can attenuate renal injury and reduce the severity of acute renal failure. This effect is obtained by increasing urine output and hence, facilitating fluid, acid-base and potassium control.2 This effect is obtained by the increase in the excretion of urinary sodium and chloride.3 D0J9XZ DB00215 Citalopram small molecule approved 59729-33-8 324.3919 C20H21FN2O P31645#Sodium-dependent serotonin transporter@P70174#Histamine H1 receptor Citalopram belongs to a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). It has been found to relieve or manage symptoms of depression, anxiety, eating disorders and obsessive-compulsive disorder among other mood disorders. The antidepressant, anti-anxiety, and other actions of citalopram are linked to its inhibition of CNS central uptake of serotonin Label. Serotonergic abnormalities have been reported in patients with mood disorders. Behavioral and neuropsychological of effects of serotonin include the regulation of mood, perception, reward, anger, aggression, appetite, memory, sexuality, and attention, as examples. The onset of action for depression is approximately 1 to 4 weeks. The complete response may take 8-12 weeks after initiation of citalopram 16. D0Y5DO DB00216 Eletriptan small molecule approved 143322-58-1 382.519 C22H26N2O2S P28221#5-hydroxytryptamine receptor 1D@P28222#5-hydroxytryptamine receptor 1B@P30939#5-hydroxytryptamine receptor 1F@P08908#5-hydroxytryptamine receptor 1A Eletriptan is a selective 5-hydroxytryptamine 1B/1D receptor agonist. In the anesthetized dog, eletriptan has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. While the effect on blood flow was selective for the carotid arterial bed, decreases in coronary artery diameter were observed. Eletriptan has also been shown to inhibit trigeminal nerve activity in the rat. D02DMQ DB00217 Bethanidine small molecule approved 55-73-2 177.2462 C10H15N3 P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor Bethanidine is a guanidinium antihypertensive agent that acts by blocking adrenergic transmission. The precise mode of action is not clear. Although bethanidine may produce adverse effects, they are beneficial in severe hypertension and produce fewer side effects than guanethidine. D0JP4H DB00218 Moxifloxacin small molecule approved 151096-09-2 401.4314 C21H24FN3O4 P11388#DNA topoisomerase 2-alpha@P27169#Serum paraoxonase/arylesterase 1 Moxifloxacin is a quinolone/fluoroquinolone antibiotic. Moxifloxacin can be used to treat infections caused by the following bacteria: Aerobic Gram-positive microorganisms: Corynebacterium species, Micrococcus luteus, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus warneri, Streptococcus pneumoniae, and Streptococcus viridans group. Aerobic Gram-negative microorganisms: Acinetobacter lwoffii, Haemophilus influenzae, and Haemophilus parainfluenzae. Other microorganisms: Chlamydia trachomatis. Moxifloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Moxifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. D0ZV0Z DB00219 Oxyphenonium small molecule approved 14214-84-7 348.4996 C21H34NO3 P11229#Muscarinic acetylcholine receptor M1 Oxyphenonium is an anticholinergic drug, a medication that reduces the effect of acetylcholine, a chemical released from nerves that stimulates muscles, by blocking the receptors for acetylcholine on smooth muscle (a type of muscle). It also has a direct relaxing effect on smooth muscle. Oxyphenonium is used to treat or prevent spasm in the muscles of the gastrointestinal tract in the irritable bowel syndrome. In addition, Oxyphenonium inhibits gastrointestinal propulsive motility and decreases gastric acid secretion and controls excessive pharyngeal, tracheal and bronchial secretions. D0D1MA DB00220 Nelfinavir small molecule approved 159989-64-7 567.782 C32H45N3O4S O90777#HIV-1 protease Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. DB00221 Isoetharine small molecule approved 79490-84-9 239.3107 C13H21NO3 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor Isoetharine is a relatively selective beta2-adrenergic bronchodilator. Isoetharine is indicated for the relief of bronchospasm associated with chronic obstructive pulmonary disease. Adrenergic bronchodilators are breathed in through the mouth to open up the bronchial tubes (air passages) of the lungs. D08HUC DB00222 Glimepiride small molecule approved 93479-97-1 490.62 C24H34N4O5S Q14654#ATP-sensitive inward rectifier potassium channel 11@P48048#ATP-sensitive inward rectifier potassium channel 1@Q09428#ATP-binding cassette sub-family C member 8 Glimepiride stimulates the secretion of insulin granules from the pancreatic beta cells and improves the sensitivity of peripheral tissues to insulin to increase peripheral glucose uptake, thus reducing plasma blood glucose levels and glycated hemoglobin (HbA1C) levels. A multi-center, randomized, placebo-controlled clinical trial evaluated the efficacy of glimepiride (1–8 mg) as monotherapy titrated over 10 weeks compared with placebo in T2DM subjects who were not controlled by diet alone.1 In this study, there was a reduction in fasting plasma glucose (FPG) by 46 mg/dL, post-prandial glucose (PPG) by 72 mg/dL, and HbA1c by 1.4% more than the placebo.1 In another randomized study comprising of patients with T2DM receiving either placebo or one of the three doses (1, 4, or 8 mg) of glimepiride during a 14-week study period, all glimepiride regimens significantly reduced FPG, PPG, and HbA1c values (P < 0.001) compared to placebo by the end of the study period.1 The 4- and 8-mg doses of glimepiride were more effective than the 1-mg dose; however, the 4-mg dose provided a nearly maximal antihyperglycemic effect.1 D0B2GI DB00223 Diflorasone small molecule approved 2557-49-5 410.4515 C22H28F2O5 P04150#Glucocorticoid receptor Like other topical corticosteroids, diflorasone has anti-inflammatory, antipruritic, and vasoconstrictive properties. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Diflorasone is a potent topical corticosteroid that should not be used with occlusive dressings. It is recommended that treatment should be limited to 2 consecutive weeks and therapy should be discontinued when adequate results have been achieved. D0G7KJ DB00224 Indinavir small molecule approved 150378-17-9 613.7895 C36H47N5O4 Indinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Indinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. D0V7CF DB00225 Gadodiamide small molecule approved 131410-48-5 573.66 C16H26GdN5O8 Not Available D03EEH DB00226 Guanadrel small molecule approved 40580-59-4 213.2768 C10H19N3O2 P23975#Sodium-dependent noradrenaline transporter High blood pressure adds to the work load of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled. Guanadrel works by controlling nerve impulses along certain nerve pathways. As a result, it relaxes the blood vessels so that blood passes through them more easily. This helps to lower blood pressure. DB00227 Lovastatin small molecule approved 75330-75-5 404.5396 C24H36O5 P04035#3-hydroxy-3-methylglutaryl-coenzyme A reductase@P20701#Integrin alpha-L@Q92769#Histone deacetylase 2 Lovastatin is an oral antilipemic agent which reversibly inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, lovastatin reduces the risk of cardiovascular morbidity and mortality.5,13,14,30 D06WTZ DB00228 Enflurane small molecule approved 13838-16-9 184.492 C3H2ClF5O P23415#Glycine receptor subunit alpha-1@P28472#Gamma-aminobutyric acid receptor subunit beta-3@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@Q00975#Voltage-dependent N-type calcium channel subunit alpha-1B@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A@Q15878#Voltage-dependent R-type calcium channel subunit alpha-1E Enflurane rapidly induces anesthesia via the stimulation of inhibitory neural channels and the inhibition of excitatory neural channels. Muscle relaxation, obtundation of pharyngeal and laryngeal reflexes, and lowering of blood pressure are some of the main pharmacodynamic effects of this drug.17 Enflurane also decreases cardiac muscle contractility.5 D0AO9S DB00229 Cefotiam small molecule approved 61622-34-2 525.628 C18H23N9O4S3 Cefotiam is a third generation beta-lactam cephalosporin antibiotic that works by inhibiting bacterial cell wall biosynthesis. It is a broad spectrum antibiotic that is effective against Gram positive and Gram negative bacteria. D0K3DQ DB00230 Pregabalin small molecule approved 148553-50-8 159.2261 C8H17NO2 P54289#Voltage-dependent calcium channel subunit alpha-2/delta-1 Although the structure of pregabalin is similar to gamma-aminobutyric acid (GABA), it does not bind to GABA receptors.620 Instead, it binds the alpha2-delta subunit of presynaptic voltage-gated calcium channels in the central nervous system.620 Pregabalin does not modulate dopamine receptors, serotonin receptors, opiate receptors, sodium channels or cyclooxygenase activity.20 D00WUF DB00231 Temazepam small molecule approved 846-50-4 300.74 C16H13ClN2O2 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Temazepam is a benzodiazepine used as a hypnotic agent in the management of insomnia Label 6,7,12,13,14. Temazepam produces CNS depression at limbic, thalamic, and hypothalamic levels of the CNS 6,7,13,14. Temazepam increases the affinity of the neurotransmitter gamma-aminobutyric acid (GABA) for GABA receptors by binding to benzodiazepine receptors 6,7,13,14. Results are sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action 6,7,13,14. D04BNP DB00233 Aminosalicylic acid small molecule approved 65-49-6 153.1354 C7H7NO3 P35354#Prostaglandin G/H synthase 2@O15111#Inhibitor of nuclear factor kappa-B kinase subunit alpha@P09917#Arachidonate 5-lipoxygenase@Q9NZK7#Group IIE secretory phospholipase A2 Aminosalicylic acid is an anti-mycobacterial agent used with other anti-tuberculosis drugs (most often isoniazid) for the treatment of all forms of active tuberculosis due to susceptible strains of tubercle bacilli. The two major considerations in the clinical pharmacology of aminosalicylic acid are the prompt production of a toxic inactive metabolite under acid conditions and the short serum half life of one hour for the free drug. Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis (prevents the multiplying of bacteria without destroying them). It also inhibits the onset of bacterial resistance to streptomycin and isoniazid. DB00234 Reboxetine small molecule approved 71620-89-8 313.397 C19H23NO3 P23975#Sodium-dependent noradrenaline transporter Reboxetine is a selective noradrenaline reuptake inhibitor (NaRI), the first drug of new antidepressant class. Reboxetine is an a-ariloxybenzyl derivative of morpholine. Reboxetine is primarily used to treat depression but has also been found useful in the treatment of narcolepsy and panic disorders. D0N8FQ DB00235 Milrinone small molecule approved 78415-72-2 211.2194 C12H9N3O Q14432#cGMP-inhibited 3',5'-cyclic phosphodiesterase A D0Y9ZE DB00236 Pipobroman small molecule approved 54-91-1 356.054 C10H16Br2N2O2 Pipobroman is an antineoplastic agent. Specifically, it is a piperazine derivative with a chemical structure close to that of many DNA alkylating agents. Pipobroman has well-documented clinical activity against polycythemia vera and essential thrombocythemia. D03FNJ DB00237 Butabarbital small molecule approved 125-40-6 212.2456 C10H16N2O3 P39086#Glutamate receptor ionotropic, kainate 1@Q13002#Glutamate receptor ionotropic, kainate 2@P42262#Glutamate receptor 2@P28472#Gamma-aminobutyric acid receptor subunit beta-3@P32297#Neuronal acetylcholine receptor subunit alpha-3@P43681#Neuronal acetylcholine receptor subunit alpha-4@P36544#Neuronal acetylcholine receptor subunit alpha-7@Q9UGM1#Neuronal acetylcholine receptor subunit alpha-9@P17787#Neuronal acetylcholine receptor subunit beta-2@P30926#Neuronal acetylcholine receptor subunit beta-4 Butabarbital potentiates GABAergic neurons while inhibiting neuronal acetylcholine and glutamate receptors to produce sedation.8,10 Butabarbital is an intermediate acting barbiturate with a duration of action of approximately 6-8 hours.12 The therapeutic index is quite wide as doses vary considerably from patient to patient.12 Patients should be counselled regarding the risk of worsening insomnia, drowsiness, falls, and complex behaviour while not fully awake.12 D0A4JK DB00238 Nevirapine small molecule approved 129618-40-2 266.2979 C15H14N4O Q72547#Reverse transcriptase/RNaseH Nevirapine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by nevirapine. Nevirapine is, in general, only prescribed after the immune system has declined and infections have become evident. It is always taken with at least one other HIV medication such as Retrovir or Videx. The virus can develop resistance to nevirapine if the drug is taken alone, although even if used properly, nevirapine is effective for only a limited time. D0O2EM DB00239 Oxiconazole small molecule approved 64211-45-6 429.12 C18H13Cl4N3O Q04782#Lanosterol synthase@O75469#Nuclear receptor subfamily 1 group I member 2 Oxiconazole is a broad-spectrum imidazole derivative whose antifungal activity is derived primarily from the inhibition of ergosterol biosynthesis, which is critical for cellular membrane integrity. It has fungicidal or fungistatic activity in vitro against a number of pathogenic fungi including the following dermatophytes, and yeasts: T. rubrum, T. mentagrophytes, T. tonsurans, T. violaceum, E. floccosum, M. canis, M. audouini, M. gypseum, C. albicans, and M. furfur. D04GYO DB00240 Alclometasone small molecule approved 67452-97-5 408.916 C22H29ClO5 P04150#Glucocorticoid receptor Alclometasone is a synthetic corticosteroid for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents. Alclometasone is a selective glucocorticoid receptor agonist. D0F1EX DB00241 Butalbital small molecule approved 77-26-9 224.2563 C11H16N2O3 P47869#Gamma-aminobutyric acid receptor subunit alpha-2@P34903#Gamma-aminobutyric acid receptor subunit alpha-3@P48169#Gamma-aminobutyric acid receptor subunit alpha-4@P31644#Gamma-aminobutyric acid receptor subunit alpha-5@Q16445#Gamma-aminobutyric acid receptor subunit alpha-6@P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P43681#Neuronal acetylcholine receptor subunit alpha-4@P36544#Neuronal acetylcholine receptor subunit alpha-7@P42262#Glutamate receptor 2@Q13002#Glutamate receptor ionotropic, kainate 2 Butalbital is a short to intermediate-acting barbiturate that reversibly depresses the activity of excitable tissues, including the central nervous system in a nonselective manner.1 Barbiturates exhibit muscle-relaxing and anti-anxiety properties 3 and they are capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma.11 The sedative dose of butalbital in nontolerant individuals is 5-100 mg and the hypnotic dose is 100-200 mg.8 Pain perception and reaction are relatively unimpaired until the moment of unconsciousness.1 In some cases, an unwanted paradoxical response of excitement may be observed instead of sedation with barbiturate treatment, which may be due to their depressant effects on inhibitory centers of the CNS.1 At sufficiently high therapeutic doses, barbiturates induce anesthesia; however, barbiturates are reported to lose their effectiveness for sleep induction and sleep maintenance after 2 weeks.11 Barbiturates are habit-forming; they can produce tolerance and both dependence and addiction, which is partly explained by decreased drug concentration at the site of action due to enhanced drug metabolism by induced enzymes, or to cellular adaptive changes. In addition, butalbital may lead to analgesic overuse headache.1 D05BQK DB00242 Cladribine small molecule approved 4291-63-8 285.687 C10H12ClN5O3 P00491#Purine nucleoside phosphorylase@P23921#Ribonucleoside-diphosphate reductase large subunit@P09884#DNA polymerase alpha catalytic subunit@P31350#Ribonucleoside-diphosphate reductase subunit M2@Q7LG56#Ribonucleoside-diphosphate reductase subunit M2 B@P56282#DNA polymerase epsilon subunit 2 D05GJW DB00243 Ranolazine small molecule approved 95635-55-5 427.5365 C24H33N3O4 P08588#Beta-1 adrenergic receptor@Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha@Q9NY72#Sodium channel subunit beta-3@Q8IWT1#Sodium channel subunit beta-4@P48050#Inward rectifier potassium channel 4@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4 Ranolazine exerts both antianginal and ischemic effects independent from lowering heart rate or blood pressure.9,17 It blocks IKr, the rapid portion of the delayed rectifier potassium current, and prolongs the QTc interval in a dose-dependent fashion. The Ikr is important for cardiac repolarization.17 Ranolazine exerts its therapeutic effects without negative chronotropic, dromotropic, or inotropic actions neither at rest, nor during exercise.1 D03HYQ DB00244 Mesalazine small molecule approved 89-57-6 153.1354 C7H7NO3 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1@P09917#Arachidonate 5-lipoxygenase@P37231#Peroxisome proliferator-activated receptor gamma@O15111#Inhibitor of nuclear factor kappa-B kinase subunit alpha@O14920#Inhibitor of nuclear factor kappa-B kinase subunit beta@P05164#Myeloperoxidase Mesalazine is one of the two components of sulphasalazine, the other being sulphapyridine. It is the latter which is responsible for the majority of the side effects associated with sulphasalazine therapy whilst mesalazine is known to be the active moiety in the treatment of ulcerative colitis 3. D0C4YC DB00245 Benzatropine small molecule approved 86-13-5 307.4293 C21H25NO P11229#Muscarinic acetylcholine receptor M1@Q01959#Sodium-dependent dopamine transporter@P70174#Histamine H1 receptor@P31645#Sodium-dependent serotonin transporter@P23975#Sodium-dependent noradrenaline transporter The inhibition of dopamine reuptake by benztropine produces a dose-dependent increase of dopamine in the nerve terminal of the dopaminergic system.5 DB00246 Ziprasidone small molecule approved 146939-27-7 412.936 C21H21ClN4OS P21728#D(1A) dopamine receptor@P20309#Muscarinic acetylcholine receptor M3@P08913#Alpha-2A adrenergic receptor@P35367#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor@P28222#5-hydroxytryptamine receptor 1B Ziprasidone is classified as a "second generation" or "atypical" antipsychotic and is a dopamine and 5HT2A receptor antagonist with a unique receptor binding profile. As previously mentioned, ziprasidone has a very high 5-HT2A/D2 affinity ratio, binds to multiple serotonin receptors in addition to 5-HT2A, and blocks monoamine transporters which prevents 5HT and NE reuptake. On the other hand, ziprasidone has a low affinity for muscarinic cholinergic M1, histamine H1, and alpha1-adrenergic receptors.4 D0R1JV DB00247 Methysergide small molecule approved 361-37-5 353.458 C21H27N3O2 P41595#5-hydroxytryptamine receptor 2B@P28335#5-hydroxytryptamine receptor 2C@P28223#5-hydroxytryptamine receptor 2A@P08908#5-hydroxytryptamine receptor 1A@P34969#5-hydroxytryptamine receptor 7@P28222#5-hydroxytryptamine receptor 1B@P30939#5-hydroxytryptamine receptor 1F@P28566#5-hydroxytryptamine receptor 1E Methysergide has been shown, in vitro and in vivo, to inhibit or block the effects of serotonin, a substance which may be involved in the mechanism of vascular headaches. Serotonin has been variously described as a central neurohumoral agent or chemical mediator, as a "headache substance" acting directly or indirectly to lower pain threshold, as an intrinsic "motor hormone" of the gastrointestinal tract, and as a "hormone" involved in connective tissue reparative processes. D0O6GC DB00248 Cabergoline small molecule approved 81409-90-7 451.6043 C26H37N5O2 P21728#D(1A) dopamine receptor@P08588#Beta-1 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P41595#5-hydroxytryptamine receptor 2B@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P07550#Beta-2 adrenergic receptor@P14416#D(2) dopamine receptor@P28222#5-hydroxytryptamine receptor 1B@P21728#D(1A) dopamine receptor Cabergoline stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects. Five dopamine receptor types from two dopaminergic subfamilies have been identified. The dopaminergic D1 receptor subfamily consists of D1 and D5 subreceptors, which are associated with dyskinesias. The dopaminergic D2 receptor subfamily consists of D2, D3 and D4 subreceptors, which are associated with improvement of symptoms of movement disorders. Thus, agonist activity specific for D2 subfamily receptors, primarily D2 and D3 receptor subtypes, are the primary targets of dopaminergic antiparkinsonian agents. It is thought that postsynaptic D2 stimulation is primarily responsible for the antiparkinsonian effect of dopamine agonists, while presynaptic D2 stimulation confers neuroprotective effects. This semisynthetic ergot derivative exhibits potent agonist activity on dopamine D2- and D3-receptors. It also exhibits: agonist activity (in order of decreasing binding affinities) on 5-hydroxytryptamine (5-HT)2B, 5-HT2A, 5-HT1D, dopamine D4, 5-HT1A, dopamine D1, 5-HT1B and 5-HT2C receptors and antagonist activity on α2B, α2A, and α2C receptors. Parkinsonian Syndrome manifests when approximately 80% of dopaminergic activity in the nigrostriatal pathway of the brain is lost. As this striatum is involved in modulating the intensity of coordinated muscle activity (e.g. movement, balance, walking), loss of activity may result in dystonia (acute muscle contraction), Parkinsonism (including symptoms of bradykinesia, tremor, rigidity, and flattened affect), akathesia (inner restlessness), tardive dyskinesia (involuntary muscle movements usually associated with long-term loss of dopaminergic activity), and neuroleptic malignant syndrome, which manifests when complete blockage of nigrostriatal dopamine occurs. High dopaminergic activity in the mesolimbic pathway of the brain causes hallucinations and delusions; these side effects of dopamine agonists are manifestations seen in patients with schizophrenia who have overractivity in this area of the brain. The hallucinogenic side effects of dopamine agonists may also be due to 5-HT2A agonism. The tuberoinfundibular pathway of the brain originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits lactotrophs in anterior pituitary from secreting prolactin. Increased dopaminergic activity in the tuberoinfundibular pathway inhibits prolactin secretion. D04EGX DB00249 Idoxuridine small molecule approved 54-42-2 354.0985 C9H11IN2O5 P13159#Thymidine kinase In chemical structure idoxuridine closely approximates the configuration of thymidine, one of the four building blocks of DNA (the genetic material of the Herpes virus). As a result, idoxuridine is able to replace thymidine in the enzymatic step of viral replication or "growth". The consequent production of faulty DNA results in a pseudostructure which cannot infect or destroy tissue. In short, by pre-empting a vital building block in the genetic material of the Herpes simplex virus, Herplex-D topical solution destroys the infective and destructive capacity of the viral material. The virus infected cell may only be attacked during the period of active synthesis of DNA. This occurs early in the development of the Herpes simplex lesion, but at different times in different cells. Therefore, ideally, the affected area should remain saturated with the antiviral agent. D09PZO DB00250 Dapsone small molecule approved 80-08-0 248.301 C12H12N2O2S Dapsone is a sulfone with anti-inflammatory immunosuppressive properties as well as antibacterial and antibiotic properties. Dapsone is the principal drug in a multidrug regimen recommended by the World Health Organization for the treatment of leprosy. As an anti-infective agent, it is also used for treating malaria and, recently, for Pneumocystic carinii pneumonia in AIDS patients. Dapsone is absorbed rapidly and nearly completely from the gastrointestinal tract. Dapsone is distributed throughout total body water and is present in all tissues. However, it tends to be retained in skin and muscle and especially in the liver and kidney: traces of the drug are present in these organs up to 3 weeks after therapy cessation. D0MA9N DB00251 Terconazole small molecule approved 67915-31-5 532.462 C26H31Cl2N5O3 Terconazole is a triazole antifungal agent available for intravaginal use. It is structurally related to imidazole-derivative antifungal agents, although terconazole and other triazoles have 3 nitrogens in the azole ring. By inhibiting the 14-alpha-demethylase (lanosterol 14-alpha-demethylase), Terconazole inhibits ergosterol synthesis. Depletion of ergosterol in fungal membrane disrupts the structure and many functions of fungal membrane leading to inhibition of fungal growth. D01AQT DB00252 Phenytoin small molecule approved 57-41-0 252.268 C15H12N2O2 Q12809#Potassium voltage-gated channel subfamily H member 2@Q14524#Sodium channel protein type 5 subunit alpha@O75469#Nuclear receptor subfamily 1 group I member 2@Q99250#Sodium channel protein type 2 subunit alpha@P28472#Gamma-aminobutyric acid receptor subunit beta-3@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A Phenytoin is an anticonvulsant with a narrow therapeutic index.5 Although the recommended therapeutic range is cited to be between 10-20 mg/L, differences in albumin levels, genetics, comorbidities, and body composition can make achieving an ideal phenytoin dose challenging.5 For example, studies have confirmed that phenytoin metabolism is impacted by CYP2C9 genotype polymorphisms and possibly by CYP2C19 genotype polymorphisms (the latter has not been as extensively studied).5 D0E4DW DB00253 Medrysone small molecule approved 2668-66-8 344.4877 C22H32O3 P04150#Glucocorticoid receptor Medrysone is a topical anti-inflammatory corticoidsteroids for ophthalmic use. In patients with increased intraocular pressure and in those susceptible to a rise in intraocular pressure, there is less effect on pressure with medrysone than with dexamethasone or betamethasone. Corticoidsteroids inhibit the edema, fibrin deposition, capillary dilation, and phagocytic migration of the acute inflammatory response, as well as capillary proliferation, deposition of collagen, and scar formation. D04SFH DB00254 Doxycycline small molecule approved 564-25-0 444.4346 C22H24N2O8 The tetracyclines, including doxycycline, are mainly bacteriostatic and are thought to exert antimicrobial effects by the inhibition of protein synthesis. Bacteriostatic antibiotics suppress the growth of bacteria, or keep them in the stationary phase of growth 4. The tetracyclines, including doxycycline, have a similar antimicrobial spectrum of activity against a variety of gram-positive and gram-negative microorganisms, treating numerous infectious diseases. Cross-resistance of these microorganisms to tetracyclines is a common occurrence Label. Doxycycline shows favorable intra-cellular penetration, with bacteriostatic activity on a wide range of bacteria 5. Doxycycline has antiparasitic effects 2, 3, 4. In addition to the above effects, this drug has demonstrated anti-inflammatory actions, which may help to manage inflammatory conditions such as rosacea 6. D0S0LZ DB00255 Diethylstilbestrol small molecule approved 56-53-1 268.356 C18H20O2 P03372#Estrogen receptor@P10275#Androgen receptor@P04278#Sex hormone-binding globulin@Q92731#Estrogen receptor beta@O75469#Nuclear receptor subfamily 1 group I member 2@P62508#Estrogen-related receptor gamma@P11474#Steroid hormone receptor ERR1@Q15596#Nuclear receptor coactivator 2@O95718#Steroid hormone receptor ERR2 Diethylstilbestrol is a synthetic estrogen that was developed to supplement a woman's natural estrogen production. In 1971, the Food and Drug Administration (FDA) issued a Drug Bulletin advising physicians to stop prescribing DES to pregnant women because it was linked to a rare vaginal cancer in female offspring. D0Y2NE DB00256 Lymecycline small molecule approved 992-21-2 602.6328 C29H38N4O10 P0A7V8#30S ribosomal protein S4 Lymecycline, like other tetracyclines, exerts bacteriostatic actions on intracellular and extracellular bacteria, treating susceptible bacterial infections.9 It has been shown to be safe and effective in the treatment of moderate to severe acne.1 D04VEJ DB00257 Clotrimazole small molecule approved 23593-75-1 344.837 C22H17ClN2 O15554#Intermediate conductance calcium-activated potassium channel protein 4@O75469#Nuclear receptor subfamily 1 group I member 2@Q8TDS4#Hydroxycarboxylic acid receptor 2 Clotrimazole is a broad-spectrum antifungal agent that inhibits the growth of pathogenic yeasts by changing the permeability of cell membranes. The action of clotrimazole is fungistatic at concentrations of drug up to 20 mcg/mL and may be fungicidal in vitro against Candida albicans and other species of the genus Candida at higher concentrations Label. Unfortunately, resistance to clotrimazole, which was rare in the past, is now common in various patient populations 2. D09GOS DB00258 Calcium acetate small molecule approved 62-54-4 158.166 C4H6CaO4 Patients with advanced renal insufficiency (creatinine clearance less than 30 ml/min) exhibit phosphate retention and some degree of hyperphosphatemia. The retention of phosphate plays a pivotal role in causing secondary hyperparathyroidism associated with osteodystrophy, and soft-tissue calcification. The mechanism by which phosphate retention leads to hyperparathyroidism is not clearly delineated. Therapeutic efforts directed toward the control of hyperphosphatemia include reduction in the dietary intake of phosphate, inhibition of absorption of phosphate in the intestine with phosphate binders, and removal of phosphate from the body by more efficient methods of dialysis. The rate of removal of phosphate by dietary manipulation or by dialysis is insufficient. Dialysis patients absorb 40% to 80% of dietary phosphorus. Therefore, the fraction of dietary phosphate absorbed from the diet needs to be reduced by using phosphate binders in most renal failure patients on maintenance dialysis. Calcium acetate when taken with meals combines with dietary phosphate to form insoluble calcium phosphate which is excreted in the feces. Maintenance of serum phosphorus below 6.0 mg/dl is generally considered as a clinically acceptable outcome of treatment with phosphate binders. Calcium acetate is highly soluble at neutral pH, making the calcium readily available for binding to phosphate in the proximal small intestine. DB00259 Sulfanilamide small molecule approved 63-74-1 172.205 C6H8N2O2S P0AC13#Dihydropteroate synthase Sulfanilamide is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus. D0L4JT DB00260 Cycloserine small molecule approved 68-41-7 102.0919 C3H6N2O2 P10724#Alanine racemase Cycloserine, a broad-spectrum antibiotic, may be bactericidal or bacteriostatic, depending on its concentration at the site of infection and the susceptibility of the organism. Cycloserine works by blocking the formation of these peptidoglycans. By doing this the walls of the bacteria become weak and it results in the death of the bacteria D02WFK DB00261 Anagrelide small molecule approved 68475-42-3 256.088 C10H7Cl2N3O Q14432#cGMP-inhibited 3',5'-cyclic phosphodiesterase A Anagrelide decreases platelet counts by suppressing transcription factors necessary for the synthesis and maturation of platelet-producing cells.9 The drug itself appears to have a relatively short residence time in the body necessitating twice or four times daily dosing. However, given that the pharmacological effect of anagrelide therapy is reliant on a gradual suppression of platelet-producing cells, it may take 7 to 14 days11 for its administration to be reflected in reduced platelet counts - for this reason any changes to anagrelide doses should not exceed 0.5 mg/day in any one week.9 D0D1HW DB00262 Carmustine small molecule approved 154-93-8 214.05 C5H9Cl2N3O2 P00390#Glutathione reductase, mitochondrial Carmustine is one of the nitrosoureas indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in treatment of brain tumors, multiple myeloma, Hodgkin's disease, and non-Hodgkin's lymphomas. Although it is generally agreed that carmustine alkylates DNA and RNA, it is not cross resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins. DB00263 Sulfisoxazole small molecule approved 127-69-5 267.304 C11H13N3O3S P0AC13#Dihydropteroate synthase Sulfisoxazole is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus. D09TBD DB00264 Metoprolol small molecule approved 51384-51-1 267.3639 C15H25NO3 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor Administration of metoprolol in normal subjects is widely reported to produce a dose-dependent reduction on heart rate and cardiac output.1 This effect is generated due to a decreased cardiac excitability, cardiac output, and myocardial oxygen demand.6 In the case of arrhythmias, metoprolol produces its effect by reducing the slope of the pacemaker potential as well as suppressing the rate of atrioventricular conduction.7 D0I2MK DB00265 Crotamiton small molecule approved 483-63-6 203.2802 C13H17NO Crotamiton is usually used to treat pruritis (itching of the skin) caused by scabies or sunburn. Crotamiton relieves itching by producing what is called a counter-irritation. As crotamiton evaporates from the skin, it produces a cooling effect. This cooling effect helps to divert your body's attention away from the itching. Due to this cooling effect it is also effective for the relief of sunburn. The drug is also believed to kill scabies through an unknown mechanism. D0T3NY DB00266 Dicoumarol small molecule approved 66-76-2 336.295 C19H12O6 Q9BQB6#Vitamin K epoxide reductase complex subunit 1@Q08257#Quinone oxidoreductase Dicumarol is an coumarin-like compound found in sweet clover. It is used as an oral anticoagulant and acts by inhibiting the hepatic synthesis of vitamin K-dependent coagulation factors (prothrombin and factors VII, IX, and X). DB00267 Cefmenoxime small molecule approved 65085-01-0 511.558 C16H17N9O5S3 Cefmenoxime is a semisynthetic beta-lactam cephalosporin antibiotic with activity similar to that of cefotaxime. It has broad spectrum activity against Gram positive and Gram negative bacteria. D06QCC DB00268 Ropinirole small molecule approved 91374-21-9 260.3746 C16H24N2O P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Effects on Parkinson's and restless leg syndrome D0R9EQ DB00270 Isradipine small molecule approved 75695-93-1 371.3871 C19H21N3O5 Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@P54289#Voltage-dependent calcium channel subunit alpha-2/delta-1@Q08289#Voltage-dependent L-type calcium channel subunit beta-2@O95180#Voltage-dependent T-type calcium channel subunit alpha-1H@Q9NY47#Voltage-dependent calcium channel subunit alpha-2/delta-2@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S Isradipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of isradipine result in an overall decrease in blood pressure. D0Z7KE DB00271 Diatrizoate small molecule approved 117-96-4 613.9136 C11H9I3N2O4 Diatrizoate is the most commonly used water-soluble, iodinated, radiopaque x-ray contrast medium. Radiopaque agents are drugs used to help diagnose certain medical problems. They contain iodine, which blocks x-rays. Depending on how the radiopaque agent is given, it localizes or builds up in certain areas of the body. The resulting high level of iodine allows the x-rays to make a "picture" of the area. The areas of the body in which the radiopaque agent localizes will appear white on the x-ray film. This creates the needed distinction, or contrast, between one organ and other tissues. The contrast will help the doctor see any special conditions that may exist in that organ or part of the body. D0T9DT DB00272 Betazole small molecule approved 105-20-4 111.1451 C5H9N3 P25021#Histamine H2 receptor Betazole is a histamine H2 agonist used in a test for measuring maximal production of gastric acidity or anacidity. This measurement can be used to diagnose diseases such as Zollinger-Ellison syndrome, whereby the volume of gastric and basal secretions is measured following betazole administration (greater than 60% of the maximal acid secretion following betazole stimulation). In another test, gastritis can be diagnosed given late absence of gastric acid which is unresponsive to betazole stimulation. Betazole can be used as a gastric secretory stimulant instead of histamine with the advantage of not provoking side effects and thus not requiring the use of antihistaminic compounds. D01OUE DB00273 Topiramate small molecule approved 97240-79-4 339.362 C12H21NO8S P00918#Carbonic anhydrase 2@P22748#Carbonic anhydrase 4@Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@P39086#Glutamate receptor ionotropic, kainate 1@Q13002#Glutamate receptor ionotropic, kainate 2 Topiramate prevents the occurrence of seizures and prevents migraine symptoms by reducing neural pathway excitability.8,19 It is important to note that this drug may cause metabolic acidosis, mood changes, suicidal thoughts and attempts, as well as kidney stones. When topiramate is combined with valproic acid, it is known to cause hypothermia.19 D07VDZ DB00274 Cefmetazole small molecule approved 56796-20-4 471.534 C15H17N7O5S3 P02919#Penicillin-binding protein 1B@P0AEB2#D-alanyl-D-alanine carboxypeptidase DacA@P08506#D-alanyl-D-alanine carboxypeptidase DacC Cefmetazole is a second-generation cephalosporin. The cephalosporins are bactericidal drugs with both gram-positive and gram-negative activity. They inhibit bacterial cell wall synthesis in a way similar to the penicillins. Cefmetazole is more active than 1st-generation cephalosporins against indole-positive Proteus, Serratia, anaerobic gram-negative bacilli (including B. fragilis), and some E. coli, Klebsiella, and P. mirabilis, but is less active than cefoxitin or cefotetan against most gram-negative bacilli. D05UBX DB00275 Olmesartan small molecule approved 144689-24-7 446.5016 C24H26N6O3 P30556#Type-1 angiotensin II receptor Overall, olmesartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium. DB00276 Amsacrine small molecule approved 51264-14-3 393.459 C21H19N3O3S P11388#DNA topoisomerase 2-alpha@Q12809#Potassium voltage-gated channel subfamily H member 2@P02763#Alpha-1-acid glycoprotein 1@P02768#Serum albumin Amsacrine is an aminoacridine derivative that is a potent intercalating antineoplastic agent. It is effective in the treatment of acute leukemias and malignant lymphomas, but has poor activity in the treatment of solid tumors. It is frequently used in combination with other antineoplastic agents in chemotherapy protocols. It produces consistent but acceptable myelosuppression and cardiotoxic effects. D0G9YH DB00277 Theophylline small molecule approved 58-55-9 180.164 C7H8N4O2 O76074#cGMP-specific 3',5'-cyclic phosphodiesterase@Q14432#cGMP-inhibited 3',5'-cyclic phosphodiesterase A@Q07343#cAMP-specific 3',5'-cyclic phosphodiesterase 4B@P29274#Adenosine receptor A2a@P27815#cAMP-specific 3',5'-cyclic phosphodiesterase 4A@P09874#Poly [ADP-ribose] polymerase 1@Q92769#Histone deacetylase 2 Theophylline, an xanthine derivative chemically similar to caffeine and theobromine, is used to treat asthma and bronchospasm. Theophylline has two distinct actions in the airways of patients with reversible (asthmatic) obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects). D0F8RA DB00278 Argatroban small molecule approved 74863-84-6 508.64 C23H36N6O5S P00734#Prothrombin D07UWV DB00279 Liothyronine small molecule approved 6893-02-3 650.9735 C15H12I3NO4 P10827#Thyroid hormone receptor alpha@P10828#Thyroid hormone receptor beta@P12004#Proliferating cell nuclear antigen In hormonal replacement, liothyronine is more potent and present a faster action when compared to levothyroxine but the time of action is significantly shorter. The type of treatment needs to be well evaluated as the fast correction of thyroid hormones in certain diseases presents additional risks such as heart failure.3 The onset of activity is observed a few hours after administration and the maximum effect is observed after 2-3 days.Label D0S6JG DB00280 Disopyramide small molecule approved 3737-09-5 339.4745 C21H29N3O Q14524#Sodium channel protein type 5 subunit alpha@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@Q9NZV8#Potassium voltage-gated channel subfamily D member 2@Q9UK17#Potassium voltage-gated channel subfamily D member 3@Q12809#Potassium voltage-gated channel subfamily H member 2@P19652#Alpha-1-acid glycoprotein 2 Disopyramide is an anti-arrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. At therapeutic plasma levels, disopyramide shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs. D0M4YC DB00281 Lidocaine small molecule approved 137-58-6 234.3373 C14H22N2O Q9Y5Y9#Sodium channel protein type 10 subunit alpha@Q15858#Sodium channel protein type 9 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha@P00533#Epidermal growth factor receptor@P35499#Sodium channel protein type 4 subunit alpha@P02763#Alpha-1-acid glycoprotein 1@P19652#Alpha-1-acid glycoprotein 2 Excessive blood levels of lidocaine can cause changes in cardiac output, total peripheral resistance, and mean arterial pressure 10,7. With central neural blockade these changes may be attributable to the block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present 10,7. The net effect is normally a modest hypotension when the recommended dosages are not exceeded 10,7. D0X4RN DB00282 Pamidronic acid small molecule approved 40391-99-9 235.0695 C3H11NO7P2 P14324#Farnesyl pyrophosphate synthase@O95749#Geranylgeranyl pyrophosphate synthase@P42574#Caspase-3@P55211#Caspase-9 Pamidronic acid is a second generation, nitrogen containing bisphosphonate that inhibits osteoclast mediated bone loss2,3,11 It has a wide therapeutic index and a long duration of action as it can be given every 3-4 weeks for certain indications.11 Patients should be counselled regarding the risk of elevated blood urea nitrogen, renal tubular necrosis, and nephrotoxicity.11 DB00283 Clemastine small molecule approved 15686-51-8 343.89 C21H26ClNO P70174#Histamine H1 receptor Clemastine is an antihistamine that also induces anticholinergic and sedative effects. Antihistamines competitively antagonize various physiological effects of histamine including increased capillary permeability and dilatation, the formation of edema, the "flare" and "itch" response, and gastrointestinal and respiratory smooth muscle constriction. Within the vascular tree, H1- receptor antagonists inhibit both the vasoconstrictor and vasodilator effects of histamine. Depending on the dose, H1- receptor antagonists can produce CNS stimulation or depression. Most antihistamines exhibit central and/or peripheral anticholinergic activity. Antihistamines act by competitively blocking H1- receptor sites. Antihistamines do not pharmacologically antagonize or chemically inactivate histamine, nor do they prevent the release of histamine. D0C5XC DB00284 Acarbose small molecule approved 56180-94-0 645.608 C25H43NO18 O43451#Maltase-glucoamylase, intestinal@P14410#Sucrase-isomaltase, intestinal@P04746#Pancreatic alpha-amylase@P10253#Lysosomal alpha-glucosidase Acarbose is a complex oligosaccharide that competitively inhibits the ability of brush-border alpha-glucosidase enzymes to break down ingested carbohydrates into absorbable monosaccharides, reducing carbohydrate absorption and subsequent postprandial insulin levels.4 Acarbose requires the co-administration of carbohydrates in order to exert its therapeutic effect, and as such should be taken with the first bite of a meal three times daily.7 D0AD5C DB00285 Venlafaxine small molecule approved 93413-69-5 277.4018 C17H27NO2 P31645#Sodium-dependent serotonin transporter@P23975#Sodium-dependent noradrenaline transporter@Q01959#Sodium-dependent dopamine transporter The mechanism of venlafaxine's (and its metabolite, O-desmethylvenlafaxine (ODV)) antidepressant effect is believed to be due to their potentiation of neurotransmitter activity in the central nervous system through the inhibition of the reuptake of serotonin and norepinephrine from within the synapse. Venlafaxine has also been shown to weakly inhibit dopamine reuptake. Neither venlafaxine nor ODV bind to muscarinic, histaminergic, or alpha-1 adrenergic receptorsLabel; pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Hyponatremia has also been shown to occur as a result of treatment with SNRIs, and is associated with the development of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) Label,14. Venlafaxine also demonstrates a clinically significant and dose-related effect on blood pressure, likely due to its potentiation of norepinephrine Label,15. D0P1UX DB00287 Travoprost small molecule approved 157283-68-6 500.5477 C26H35F3O6 P43088#Prostaglandin F2-alpha receptor Travoprost, an isopropyl ester prodrug, is a synthetic prostaglandin F2 alpha analog that is rapidly hydrolyzed by esterases in the cornea to its biologically active free acid Label. The travoprost free acid is potent and highly selective for the FP prostanoid receptor Label. D09CZA DB00288 Amcinonide small molecule approved 51022-69-6 502.5717 C28H35FO7 P04150#Glucocorticoid receptor@P04083#Annexin A1 Amcinonide is a topical corticosteroid. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and antipruritic agents. Amcinonide reduces or inhibits the actions of chemicals in the body that cause inflammation, redness, and swelling. The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man. When in an ointment form, amcinonide also helps the skin maintain moisture. D06XHC DB00289 Atomoxetine small molecule approved 83015-26-3 255.3547 C17H21NO P23975#Sodium-dependent noradrenaline transporter@P31645#Sodium-dependent serotonin transporter@P48549#G protein-activated inward rectifier potassium channel 1@P41145#Kappa-type opioid receptor Atomoxetine is a selective norepinephrine (NE) reuptake inhibitor used for the treatment of attention deficit hyperactivity disorder (ADHD). Atomoxetine has been shown to specifically increase norepinephrine and dopamine within the prefrontal cortex, which results in improved ADHD symptoms.8,8,18 D04CRN DB00290 Bleomycin small molecule approved 11056-06-7 1415.552 C55H84N17O21S3 P18858#DNA ligase 1@P49916#DNA ligase 3 Bleomycin is an antibiotic which has been shown to have antitumor activity. Bleomycin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. Bleomycin has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2. The antibiotic antitumor drugs are cell cycle-nonspecific except for Bleomycin (which has major effects in G2 and M phases). D06UVD DB00291 Chlorambucil small molecule approved 305-03-3 304.212 C14H19Cl2NO2 D0V8QT DB00292 Etomidate small molecule approved 33125-97-2 244.289 C14H16N2O2 P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P18089#Alpha-2B adrenergic receptor Etomidate is a non-barbiturate hypnotic that acts at the level of the reticular-activating system to produce anesthesia. Etomidate is an imidazole compound that appears to depress CNS function via GABA. Duration of action is intermediate between thiopental and methohexital, and recovery from a single dose is rapid with little residual depression. Like the barbiturates and propofol, etomidate is does not induce analgesia. Etomidate induces unconsciousness within one circulation time. Recovery is rapid as a result of extensive redistribution and rapid metabolism. D02YPG DB00293 Raltitrexed small molecule approved 112887-68-0 458.488 C21H22N4O6S P04818#Thymidylate synthase D01KKQ DB00294 Etonogestrel small molecule approved 54048-10-1 324.4565 C22H28O2 P06401#Progesterone receptor Etonogestrel attains its therapeutic effect inhibiting fertility by impairing the release of the luteinizing hormone which is one of the most important reproductive hormones for ovulation. As well, etonogestrel is known to increase the viscosity of the cervical mucus hindering the passage of the spermatozoa and altering the lining in the uterus to prevent the implantation of the fertilized eggs in the endometrium.7 D02KIU DB00295 Morphine small molecule approved 57-27-2 285.3377 C17H19NO3 P35372#Mu-type opioid receptor@P41145#Kappa-type opioid receptor@P41143#Delta-type opioid receptor@Q9Y6Y9#Lymphocyte antigen 96 Morphine binding to opioid receptors blocks transmission of nociceptive signals, signals pain-modulating neurons in the spinal cord, and inhibits primary afferent nociceptors to the dorsal horn sensory projection cells.1 D0WE3O DB00296 Ropivacaine small molecule approved 84057-95-4 274.4011 C17H26N2O Q9Y5Y9#Sodium channel protein type 10 subunit alpha In contrast to most other local anesthetics, the presence of epinephrine does not affect the time of onset, duration of action, or the systemic absorption of ropivacaine.2 D09RHQ DB00297 Bupivacaine small molecule approved 38396-39-3 288.4277 C18H28N2O Q9Y5Y9#Sodium channel protein type 10 subunit alpha@P34995#Prostaglandin E2 receptor EP1 subtype Bupivacaine is a widely used local anesthetic agent. Bupivacaine is often administered by spinal injection prior to total hip arthroplasty. It is also commonly injected into surgical wound sites to reduce pain for up to 20 hours after surgery. In comparison to other local anesthetics it has a long duration of action. It is also the most toxic to the heart when administered in large doses. This problem has led to the use of other long-acting local anaesthetics:ropivacaine and levobupivacaine. Levobupivacaine is a derivative, specifically an enantiomer, of bupivacaine. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both. D0A0FL DB00298 Dapiprazole small molecule approved 72822-12-9 325.4512 C19H27N5 P35348#Alpha-1A adrenergic receptor@P25100#Alpha-1D adrenergic receptor@P35368#Alpha-1B adrenergic receptor Dapiprazole is an alpha-adrenergic blocking agent. It produces miosis by blocking the alpha-adrenergic receptors on the dilator muscle of the iris. Dapiprazole produces no significant action on ciliary muscle contraction and thus, there are no changes in the depth of the anterior chamber of the thickness of the lens. It does not alter the IOP either in normal eyes or in eyes with elevated IOP. The rate of pupillary constriction may be slightly slower in clients with brown irises than in clients with blue or green irises. D0T2IA DB00299 Penciclovir small molecule approved 39809-25-1 253.2578 C10H15N5O3 P09252#DNA polymerase catalytic subunit@P13159#Thymidine kinase Penciclovir is the active metabolite of the oral product famciclovir. The more favorable results observed with topical penciclovir versus topical acyclovir for the treatment of herpes labialis may be due to the longer intracellular half-life of penciclovir in HSV-infected cells. The activated drug inhibits the viral DNA polymerase. This impairs the ability of the virus to replicate within the cell. D07BYK DB00300 Tenofovir disoproxil small molecule approved 201341-05-1 519.448 C19H30N5O10P Q72547#Reverse transcriptase/RNaseH This drug prevents viral DNA chain elongation through inhibition of enzymes necessary for host cell infection viral replication in HIV-1 and Hepatitis B infections 9, 10. DB00301 Flucloxacillin small molecule approved 5250-39-5 453.872 C19H17ClFN3O5S Flucloxacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Flucloxacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Flucloxacillin results from the inhibition of cell wall synthesis and is mediated through flucloxacillin binding to penicillin binding proteins (PBPs). Flucloxacillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. D0Q2AT DB00302 Tranexamic acid small molecule approved 1197-18-8 157.2102 C8H15NO2 P00747#Plasminogen Tranexamic acid is an antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin.5 At much higher concentrations it behaves as a noncompetitive inhibitor of plasmin similar to aminocaproic acid, a similar antifibrinolytic which is 10-fold less potent.6 Tranexamic acid binds more strongly than aminocaproic acid to both the strong and weak receptor sites of the plasminogen molecule in a ratio corresponding to the difference in potency between the compounds. In patients with hereditary angioedema, inhibition of the formation and activity of plasmin by tranexamic acid may prevent attacks of angioedema by decreasing plasmin-induced activation of the first complement protein (C1).3 DB00303 Ertapenem small molecule approved 153832-46-3 475.515 C22H25N3O7S P02919#Penicillin-binding protein 1B@P24228#D-alanyl-D-alanine carboxypeptidase DacB@P08506#D-alanyl-D-alanine carboxypeptidase DacC Ertapenem has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. D0Q1MS DB00304 Desogestrel small molecule approved 54024-22-5 310.473 C22H30O P03372#Estrogen receptor@P06401#Progesterone receptor The effects of desogestrel are divided on reproductive including modification of luteinizing hormone and follicle stimulating hormone, declines on the onset of menstruation, and increases the viscosity of the vaginal fluid; and on metabolic that includes increase insulin secretion and resistance, increased lipase activity, and increased fat deposition.9 The effect of desogestrel on the lipids has been studied extensively and the results are contradictory. D06CGB DB00305 Mitomycin small molecule approved 50-07-7 334.3272 C15H18N4O5 Mitomycin is one of the older chemotherapy drugs, which has been around and in use for decades. It is an antibiotic which has been shown to have antitumor activity. Mitomycin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. Mitomycin has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2. D0Y0GH DB00306 Talbutal small molecule approved 115-44-6 224.2563 C11H16N2O3 P47869#Gamma-aminobutyric acid receptor subunit alpha-2@P34903#Gamma-aminobutyric acid receptor subunit alpha-3@P48169#Gamma-aminobutyric acid receptor subunit alpha-4@P31644#Gamma-aminobutyric acid receptor subunit alpha-5@Q16445#Gamma-aminobutyric acid receptor subunit alpha-6@P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P43681#Neuronal acetylcholine receptor subunit alpha-4@P36544#Neuronal acetylcholine receptor subunit alpha-7@P42262#Glutamate receptor 2@Q13002#Glutamate receptor ionotropic, kainate 2 Talbutal is a short to intermediate-acting barbiturate that is a nonselective central nervous system (CNS) depressant. As with other barbiturates, talbutal is capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. Barbiturates may also induce anesthesia at sufficiently high therapeutic doses. D0W0MF DB00307 Bexarotene small molecule approved 153559-49-0 348.4779 C24H28O2 P19793#Retinoic acid receptor RXR-alpha@P28702#Retinoic acid receptor RXR-beta@P48443#Retinoic acid receptor RXR-gamma Bexarotene is a member of a subclass of retinoids that selectively activate retinoid X receptors (RXRs). These retinoid receptors have biologic activity distinct from that of retinoic acid receptors (RARs). Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. Bexarotene selectively binds and activates retinoid X receptor subtypes (RXRα, RXRβ, RXRγ). RXRs can form heterodimers with various receptor partners such as retinoic acid receptors (RARs), vitamin D receptor, thyroid receptor, and peroxisome proliferator activator receptors (PPARs). Once activated, these receptors function as transcription factors that regulate the expression of genes that control cellular differentiation and proliferation. Bexarotene inhibits the growth in vitro of some tumor cell lines of hematopoietic and squamous cell origin. It also induces tumor regression in vivo in some animal models. D0N0RU DB00308 Ibutilide small molecule approved 122647-31-8 384.576 C20H36N2O3S Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q02641#Voltage-dependent L-type calcium channel subunit beta-1@Q12809#Potassium voltage-gated channel subfamily H member 2@P54289#Voltage-dependent calcium channel subunit alpha-2/delta-1@Q06432#Voltage-dependent calcium channel gamma-1 subunit@O00180#Potassium channel subfamily K member 1@Q9Y257#Potassium channel subfamily K member 6@Q9H252#Potassium voltage-gated channel subfamily H member 6@Q9NS40#Potassium voltage-gated channel subfamily H member 7@Q14654#ATP-sensitive inward rectifier potassium channel 11 Ibutilide prolongs the action potential duration and increases both atrial and ventricular refractoriness in vivo, i.e., class III electrophysiologic effects. Voltage clamp studies indicate that ibutilide, at nanomolar concentrations, delays repolarization by activation of a slow, inward current (predominantly sodium), rather than by blocking outward potassium currents, which is the mechanism by which most other class III antiarrhythmics act. D02MLW DB00309 Vindesine small molecule approved 53643-48-4 753.941 C43H55N5O7 D04RLY DB00310 Chlorthalidone small molecule approved 77-36-1 338.766 C14H11ClN2O4S P00915#Carbonic anhydrase 1 D09NIA DB02266 Flufenamic acid small molecule approved 530-78-9 281.2299 C14H10F3NO2 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1@P42330#Aldo-keto reductase family 1 member C3@P10275#Androgen receptor@Q07869#Peroxisome proliferator-activated receptor alpha@P37231#Peroxisome proliferator-activated receptor gamma Not Available DB02300 Calcipotriol small molecule approved 112965-21-6 412.6047 C27H40O3 P11473#Vitamin D3 receptor Calcipotriene is a synthetic analog of vitamin D. In humans, the natural supply of vitamin D depends mainly on exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol to vitamin D3 (cholecalciferol) in the skin. D01QUS DB02325 Isopropyl alcohol small molecule approved 67-63-0 60.095 C3H8O Not Available DB02362 Aminobenzoic acid small molecule approved 150-13-0 137.136 C7H7NO2 P00438#p-hydroxybenzoate hydroxylase@P20586#p-hydroxybenzoate hydroxylase Not Available DB02513 Thymol small molecule approved 89-83-8 150.2176 C10H14O Not Available D06GIP DB02530 gamma-Aminobutyric acid small molecule approved 56-12-2 103.1198 C4H9NO2 Q9UBS5#Gamma-aminobutyric acid type B receptor subunit 1@O75899#Gamma-aminobutyric acid type B receptor subunit 2@P50440#Glycine amidinotransferase, mitochondrial Not Available DB02546 Vorinostat small molecule approved 149647-78-9 264.3202 C14H20N2O3 Q9BY41#Histone deacetylase 8@Q13547#Histone deacetylase 1@Q92769#Histone deacetylase 2@O15379#Histone deacetylase 3@Q9UBN7#Histone deacetylase 6@O67135#Acetoin utilization protein Not Available D0E7PQ DB02638 Terlipressin small molecule approved 14636-12-5 1227.372 C52H74N16O15S2 P30518#Vasopressin V2 receptor@P37288#Vasopressin V1a receptor@P47901#Vasopressin V1b receptor Terlipressin is a medicine similar to a naturally occurring hormone present in the body, known as antidiuretic hormone (ADH) or vasopressin. ADH has two main effects in the body. Firstly, it causes narrowing of blood vessels (vasoconstriction), thereby limiting blood flow to a particular area of the body. It also acts on receptors in the kidney to retain water in the body, which helps to prevent excessive loss of water in the urine. D0P4VX DB02659 Cholic Acid small molecule approved 81-25-4 408.5714 C24H40O5 P00326#Alcohol dehydrogenase 1C@P22830#Ferrochelatase, mitochondrial@P54965#Choloylglycine hydrolase@Q96RI1#Bile acid receptor@P51161#Gastrotropin@P62508#Estrogen-related receptor gamma@P23141#Liver carboxylesterase 1@P00403#Cytochrome c oxidase subunit 2@P04054#Phospholipase A2 Not Available D0OR2L DB02701 Nicotinamide small molecule approved 98-92-0 122.1246 C6H6N2O P00338#L-lactate dehydrogenase A chain@Q10588#ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2@P09874#Poly [ADP-ribose] polymerase 1@P11439#Exotoxin A@Q9NXA8#NAD-dependent protein deacylase sirtuin-5, mitochondrial Not Available D06NVJ DB02703 Fusidic acid small molecule approved 6990-06-3 516.7092 C31H48O6 P13551#Elongation factor G@P62580#Chloramphenicol acetyltransferase@P00484#Chloramphenicol acetyltransferase 3 Fusidic acid is a bacteriostatic antibiotic and helps prevent bacterial growth while the immune system clears the infection. DB02772 Sucrose small molecule approved 57-50-1 342.2965 C12H22O11 Q8TE23#Taste receptor type 1 member 2@P61626#Lysozyme C@P68133#Actin, alpha skeletal muscle@Q59976#Beta-glucosidase@Q9ZEU2#Amylosucrase@Q93LQ9#Beta-lactamase@O00244#Copper transport protein ATOX1@Q9Y3I0#tRNA-splicing ligase RtcB homolog@P83689#Orange carotenoid-binding protein@P22340#Sucrose porin Not Available D08TCV DB02789 Pregnenolone small molecule approved 145-13-1 316.4776 C21H32O2 O75469#Nuclear receptor subfamily 1 group I member 2@O00204#Sulfotransferase family cytosolic 2B member 1 Not Available D0B4RU DB02893 D-Methionine small molecule approved 348-67-4 149.211 C5H11NO2S P50579#Methionine aminopeptidase 2@Q9KQN0#Transcriptional regulator, HTH_3 family Not Available D0N0KW DB02925 Piretanide small molecule approved 55837-27-9 362.4 C17H18N2O5S Q13621#Solute carrier family 12 member 1 Not Available D09NNS DB02959 Oxitriptan small molecule approved 4350-09-8 220.2246 C11H12N2O3 Q9RVD6#Tryptophan--tRNA ligase 2 The psychoactive action of 5-HTP is thought to be due to increased serotonin production in central nervous system tissue. DB03017 Lauric acid small molecule approved 143-07-7 200.3178 C12H24O2 B0B3C9#Genome polyprotein@B0B3C9#Genome polyprotein@B0B3C9#Genome polyprotein@P41235#Hepatocyte nuclear factor 4-alpha@P14555#Phospholipase A2, membrane associated@P98155#Very low-density lipoprotein receptor@Q9NZD2#Glycolipid transfer protein@P02788#Lactotransferrin@P07360#Complement component C8 gamma chain@Q9UNK4#Group IID secretory phospholipase A2 Not Available DB03085 Glycolic acid small molecule approved 79-14-1 76.0514 C2H4O3 P11413#Glucose-6-phosphate 1-dehydrogenase Not Available DB03088 Pidolic acid small molecule approved 98-79-3 129.114 C5H7NO3 P19961#Alpha-amylase 2B@P15692#Vascular endothelial growth factor A@P04746#Pancreatic alpha-amylase@P0CG04#Ig lambda-1 chain C regions@P01709#Ig lambda chain V-II region MGC@Q03403#Trefoil factor 2@Q9UKQ2#Disintegrin and metalloproteinase domain-containing protein 28@Q7SIE2#Endo-1,4-beta-xylanase@Q701N4#Keratin-associated protein 5-2@O43612#Orexin Pidolic acid is a naturally occurring but little-studied amino acid derivative that can be formed enzymatically or non-enzymatically and participates as a biological intermediate in various chemical pathways 4,7. Elevations of the acid in blood levels may be associated with problems of glutamine or glutathione metabolism 7. Pidolic acid, in general, is found in large quantities in brain tissue and other tissues in bound form, like skin 7. DB03128 Acetylcholine small molecule approved 51-84-3 146.2074 C7H16NO2 P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P36544#Neuronal acetylcholine receptor subunit alpha-7 Not Available D0Q9HF DB03147 Flavin adenine dinucleotide small molecule approved 146-14-5 785.5497 C27H33N9O15P2 Q16795#NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial@P29475#Nitric oxide synthase, brain@P20586#p-hydroxybenzoate hydroxylase@Q86YB8#ERO1-like protein beta@P00390#Glutathione reductase, mitochondrial@P9WIQ3#NADPH-ferredoxin reductase FprA@P00387#NADH-cytochrome b5 reductase 3@P28593#Trypanothione reductase@P16083#Ribosyldihydronicotinamide dehydrogenase [quinone]@P26440#Isovaleryl-CoA dehydrogenase, mitochondrial Not Available DB03166 Acetic acid small molecule approved 64-19-7 60.052 C2H4O2 Not Available DB03175 Propyl alcohol small molecule approved 71-23-8 60.095 C3H8O P61626#Lysozyme C Not Available DB03193 Stearic acid small molecule approved 57-11-4 284.4772 C18H36O2 Q07869#Peroxisome proliferator-activated receptor alpha@Q9UNK4#Group IID secretory phospholipase A2 Not Available DB03209 Oteracil small molecule approved 937-13-3 157.0843 C4H3N3O4 Not Available DB03247 Flavin mononucleotide small molecule approved 146-17-8 456.3438 C17H21N4O9P Q9UJM8#Hydroxyacid oxidase 1@Q9NVS9#Pyridoxine-5'-phosphate oxidase@Q969G6#Riboflavin kinase@P29475#Nitric oxide synthase, brain@Q9ZK53#Flavodoxin@P71278#Pentaerythritol tetranitrate reductase@P30197#Epidermin decarboxylase@O00141#Serine/threonine-protein kinase Sgk1@P16099#Trimethylamine dehydrogenase@Q9F0J6#Rubredoxin-oxygen oxidoreductase Not Available DB03255 Phenol small molecule approved 108-95-2 94.1112 C6H6O P02768#Serum albumin@P00800#Thermolysin Not Available DB00312 Pentobarbital small molecule approved 76-74-4 226.2722 C11H18N2O3 Q13002#Glutamate receptor ionotropic, kainate 2@P42262#Glutamate receptor 2@P43681#Neuronal acetylcholine receptor subunit alpha-4@O75469#Nuclear receptor subfamily 1 group I member 2@P36544#Neuronal acetylcholine receptor subunit alpha-7@P28472#Gamma-aminobutyric acid receptor subunit beta-3@Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B Pentobarbital, a barbiturate, is used for the treatment of short term insomnia. It belongs to a group of medicines called central nervous system (CNS) depressants that induce drowsiness and relieve tension or nervousness. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation. D0F0YZ DB00313 Valproic acid small molecule approved 99-66-1 144.2114 C8H16O2 Q9UKV0#Histone deacetylase 9@P45954#Short/branched chain specific acyl-CoA dehydrogenase, mitochondrial@Q02218#2-oxoglutarate dehydrogenase, mitochondrial@P51649#Succinate-semialdehyde dehydrogenase, mitochondrial@Q86DI9#Sodium channel protein@Q92769#Histone deacetylase 2@Q07869#Peroxisome proliferator-activated receptor alpha@Q03181#Peroxisome proliferator-activated receptor delta@P37231#Peroxisome proliferator-activated receptor gamma@P38936#Cyclin-dependent kinase inhibitor 1 Valproate has been shown to reduce the incidence of complex partial seizures and migraine headaches.Label,5 It also improves symptom control in bipolar mania.23 Although the exact mechanisms responsible are unknown, it is thought that valproate produces increased cortical inhibition to contribute to control of neural synchrony. It is also thought that valproate exerts a neuroprotective effect preventing damage and neural degeneration in epilepsy, migraines, and bipolar disorder. DB00314 Capreomycin small molecule approved 11003-38-6 1321.4123 C50H88N28O15 P9WJ63#16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA Capreomycin is a member of the aminoglycoside family of antibiotics. These antibiotics have the ability to kill a wide variety of bacteria, including bacteria responsible for causing tuberculosis (TB). D0E7MV DB00315 Zolmitriptan small molecule approved 139264-17-8 287.3568 C16H21N3O2 P41595#5-hydroxytryptamine receptor 2B@P28222#5-hydroxytryptamine receptor 1B D0NG7O DB00316 Acetaminophen small molecule approved 103-90-2 151.1626 C8H9NO2 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1@Q15185#Prostaglandin E synthase 3@Q8NER1#Transient receptor potential cation channel subfamily V member 1 Animal and clinical studies have determined that acetaminophen has both antipyretic and analgesic effects. This drug has been shown to lack anti-inflammatory effects. As opposed to the salicylate drug class, acetaminophen does not disrupt tubular secretion of uric acid and does not affect acid-base balance if taken at the recommended doses.23 Acetaminophen does not disrupt hemostasis and does not have inhibitory activities against platelet aggregation.Label,23 Allergic reactions are rare occurrences following acetaminophen use.23 D0U5QK DB00317 Gefitinib small molecule approved 184475-35-2 446.902 C22H24ClFN4O3 P00533#Epidermal growth factor receptor Gefitinib inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer cells. D09XZB DB00318 Codeine small molecule approved 76-57-3 299.3642 C18H21NO3 P35372#Mu-type opioid receptor@P41145#Kappa-type opioid receptor@P41143#Delta-type opioid receptor General effects D03DIG DB00319 Piperacillin small molecule approved 66258-76-2 517.555 C23H27N5O7S P0A3M6#Penicillin-binding protein 2B@Q7CRA4#Penicillin-binding protein 1b Piperacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Piperacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Piperacillin results from the inhibition of cell wall synthesis and is mediated through Piperacillin binding to penicillin binding proteins (PBPs). Piperacillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. D04ZAH DB00320 Dihydroergotamine small molecule approved 511-12-6 583.6774 C33H37N5O5 P08913#Alpha-2A adrenergic receptor@P41595#5-hydroxytryptamine receptor 2B@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor@P28222#5-hydroxytryptamine receptor 1B@P13945#Beta-3 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor DHE is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.8,9,10 It is thought to exert its therapeutic effect through both neurological and vascular mechanisms.3 Its serotonin agonist activity may contribute to decreasing glutamatergic activity of the trigeminal system and subsequent cortical depolarization which is thought to participate in the neurological pathophysiology of migraine.2 The same serotonin agonist activity also contributes to vasoconstriction, producing both the characteristic side effect of chest tightness and potentially contributing to a therapeutic effect by counteracting the vasodilation due to calcitonin gene-related peptide (CGRP) release in migraine attacks.3 D0V3ZA DB00321 Amitriptyline small molecule approved 50-48-6 277.4033 C20H23N P23975#Sodium-dependent noradrenaline transporter@P31645#Sodium-dependent serotonin transporter@P28223#5-hydroxytryptamine receptor 2A@P08908#5-hydroxytryptamine receptor 1A@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor@P04629#High affinity nerve growth factor receptor@Q16620#BDNF/NT-3 growth factors receptor@P35348#Alpha-1A adrenergic receptor@P25100#Alpha-1D adrenergic receptor Effects in pain and depression D0Y5UG DB00322 Floxuridine small molecule approved 50-91-9 246.1924 C9H11FN2O5 P04818#Thymidylate synthase Floxuridine is an anti-metabolite or a pyrimidine analog that works by disrupting the process S-phase of cell division, selectively targeting rapidly dividing cells. Due to the structural similarities, antimetabolites act as pyrimidine-like molecules and prevent normal pyrimidines from being incorporated into DNA. After successful biotransformation, floxuridine is converted into an active component, flurouracil, which blocks the enzyme which converts cytosine nucleosides into the deoxy derivative. Flurouracil also physically prevents the incorporation of thymidine nucleotides into the DNA strand by taking their place, further preventing DNA synthesis. D0TS1Z DB00323 Tolcapone small molecule approved 134308-13-7 273.2408 C14H11NO5 P21964#Catechol O-methyltransferase Tolcapone is a potent, selective, and reversible inhibitor of catechol-O-methyltransferase (COMT). In humans, COMT is distributed throughout various organs. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. COMT is responsible for the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa catalyzing it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery. When tolcapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that these sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease in patients as well as increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa. D0Y7PG DB00324 Fluorometholone small molecule approved 426-13-1 376.4617 C22H29FO4 P04150#Glucocorticoid receptor Corticosteroids such as fluorometholone inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation. D0P0HT DB00325 Nitroprusside small molecule approved 15078-28-1 215.938 C5FeN6O P16066#Atrial natriuretic peptide receptor 1 Nitroprusside a powerful vasodilator relaxes the vascular smooth muscle and produce consequent dilatation of peripheral arteries and veins. Other smooth muscle (e.g., uterus, duodenum) is not affected. Sodium nitroprusside is more active on veins than on arteries. D00PLV DB00326 Calcium glucoheptonate small molecule approved 29039-00-7 490.425 C14H26CaO16 Calcium supplements such as calcium gluceptate are taken by individuals who are unable to get enough calcium in their regular diet or who have a need for more calcium. They are used to prevent or treat several conditions that may cause hypocalcemia (not enough calcium in the blood). The body needs calcium to make strong bones. Calcium is also needed for the heart, muscles, and nervous system to work properly. The bones serve as a storage site for the body's calcium. They are continuously giving up calcium to the bloodstream and then replacing it as the body's need for calcium changes from day to day. When there is not enough calcium in the blood to be used by the heart and other organs, your body will take the needed calcium from the bones. When you eat foods rich in calcium, the calcium will be restored to the bones and the balance between your blood and bones will be maintained. DB00327 Hydromorphone small molecule approved 466-99-9 285.3377 C17H19NO3 P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor In clinical trials, hydromorphone has been shown to be suitable for pain relief in patients that do not tolerate the side effects of morphine or that suffer from renal failure or asthma. It has been shown to be 5-7 times more potent than morphine with a shorter duration of analgesia.2 D04JHN DB00328 Indomethacin small molecule approved 53-86-1 357.788 C19H16ClNO4 P35354#Prostaglandin G/H synthase 2@P14555#Phospholipase A2, membrane associated@P23219#Prostaglandin G/H synthase 1@Q8N8N7#Prostaglandin reductase 2@P37231#Peroxisome proliferator-activated receptor gamma@Q04760#Lactoylglutathione lyase@Q9Y5Y4#Prostaglandin D2 receptor 2@Q07869#Peroxisome proliferator-activated receptor alpha@P42330#Aldo-keto reductase family 1 member C3@P19525#Interferon-induced, double-stranded RNA-activated protein kinase Indometacin is an NSAID with analgesic and antipyretic properties that exerts its pharmacological effects by inhibiting the synthesis of factors involved in pain, fever, and inflammation. Its therapeutic action does not involve pituitary-adrenal stimulation.13 Indometacin primarily works by suppressing inflammation in rheumatoid arthritis by providing relief of pain as well as reducing fever, swelling, and tenderness. This effectiveness has been demonstrated by a reduction in the extent of joint swelling, the average number of joints displaying symptoms of inflammation, and the severity of morning stiffness. Increased mobility was demonstrated by a decrease in total walking time and by improved functional capability seen as an increase in grip strength.13 In clinical trials, indometacin was shown to be effective in relieving the pain, reducing the fever, swelling, redness, and tenderness of acute gouty arthritis. Due to its pharmacological actions, the use of indometacin is associated with the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, as well as gastrointestinal effects such as bleeding, ulceration, and perforation of the stomach or intestines.13 D0R1RS DB00330 Ethambutol small molecule approved 74-55-5 204.3098 C10H24N2O2 P9WNL5#Probable arabinosyltransferase C@P9WNL7#Probable arabinosyltransferase B@P9WNL9#Probable arabinosyltransferase A Ethambutol is indicated in combination with other anti-tuberculosis drugs in the treatment of pulmonary tuberculosis.12 It has a long duration of action as it is administered daily, and a moderate therapeutic window.12 Patients should be counselled regarding the risk of optic neuritis and hepatic toxicity.12 D08QME DB00331 Metformin small molecule approved 657-24-9 129.1636 C4H11N5 Q16134#Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial@Q9Y478#5'-AMP-activated protein kinase subunit beta-1 General effects D0D7LA DB00332 Ipratropium small molecule approved 60205-81-4 332.463 C20H30NO3 P20309#Muscarinic acetylcholine receptor M3@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2 Ipratropium is a short-acting agent that inhibits the parasympathetic nervous system at the level of the airway which then produces bronchodilatation. The effect of this agent starts after 1-2 hours and it is known to last only from 4 to 6 hours.3 As part of the effect, ipratropium relaxes the bronchial airways which reverse the narrowing that accounts for wheezy breathing, chest tightness, cough and abnormal gas exchange.6 D0S0AS DB00333 Methadone small molecule approved 76-99-3 309.4452 C21H27NO P41143#Delta-type opioid receptor@P43681#Neuronal acetylcholine receptor subunit alpha-4@P17787#Neuronal acetylcholine receptor subunit beta-2@P36544#Neuronal acetylcholine receptor subunit alpha-7@P32297#Neuronal acetylcholine receptor subunit alpha-3@Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B D09OJQ DB00334 Olanzapine small molecule approved 132539-06-1 312.432 C17H20N4S P14416#D(2) dopamine receptor The effect of olanzapine in the D2 receptor is reported to produce the positive effects of this drug such as a decrease in hallucinations, delusions, disorganized speech, disorganized thought, and disorganized behavior. On the other hand, its effect on the serotonin 5HT2A receptor prevents the onset of anhedonia, flat affect, alogia, avolition and poor attention.6 Based on the specific mechanism of action, olanzapine presents a higher affinity for the dopamine D2 receptor when compared to the rest of the dopamine receptor isotypes. This characteristic significantly reduces the presence of side effects.10 D0V4QS DB00335 Atenolol small molecule approved 29122-68-7 266.3361 C14H22N2O3 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor Atenolol is a cardio-selective beta-blocker and as such exerts most of its effects on the heart.Label It acts as an antagonist to sympathetic innervation and prevents increases in heart rate, electrical conductivity, and contractility in the heart due to increased release of norepinephrine from the peripheral nervous system.Label,24,14 Together the decreases in contractility and rate produce a reduction in cardiac output resulting in a compensatory increase in peripheral vascular resistance in the short-term. This response later declines to baseline with long-term use of atenolol. More importantly, this reduction in the work demanded of the myocardium also reduces oxygen demand which provides therapeutic benefit by reducing the mismatch of oxygen supply and demand in settings where coronary blood flow is limited, such as in coronary atherosclerosis. Reducing oxygen demand, particularly due to exercise, can reduce the frequency of angina pectoris symptoms and potentially improve survival of the remaining myocardium after myocardial infarction. The decrease in rate of sinoatrial node potentials, electrical conduction, slowing of potentials traveling through the atrioventricular node, and reduced frequency of ectopic potentials due to blockade of adrenergic beta receptors has led to benefit in arrhythmic conditions such as atrial fibrillation by controlling the rate of action potential generation and allowing for more effective coordinated contractions. Since a degree of sympathetic activity is necessary to maintain cardiac function, the reduced contractility induced by atenolol may precipitate or worsen heart failure, especially during volume overload.Label D01UXC DB00336 Nitrofural small molecule approved 59-87-0 198.1362 C6H6N4O4 P06715#Glutathione reductase Nitrofurazone is a topical antibacterial agent indicated as an adjunctive therapy for second and third degree burns when resistance to other agents is a real or potential problem. Nitrofurazone is also indicated in skin grafting when bacterial contamination may cause graft rejection or donor site infection, especially in hospitals with a history of resistant bacteria. DB00337 Pimecrolimus small molecule approved 137071-32-0 810.46 C43H68ClNO11 P42345#Serine/threonine-protein kinase mTOR@P62942#Peptidyl-prolyl cis-trans isomerase FKBP1A Pimecrolimus is a chemical that is used to treat atopic dermatitis (eczema). Atopic dermatitis is a skin condition characterized by redness, itching, scaling and inflammation of the skin. The cause of atopic dermatitis is not known; however, scientists believe that it may be due to activation of the immune system by various environmental or emotional triggers. Scientists do not know exactly how pimecrolimus reduces the manifestations of atopic dermatitis, but pimecrolimus reduces the action of T-cells and mast cells which are part of the immune system and contribute to responses of the immune system. Pimecrolimus prevents the activation of T-cells by blocking the effects of chemicals (cytokines) released by the body that stimulate T-cells. Pimecrolimus also reduces the ability of mast cells to release chemicals that promote inflammation. D0Z4UN DB00338 Omeprazole small molecule approved 73590-58-6 345.416 C17H19N3O3S P20648#Potassium-transporting ATPase alpha chain 1@P35869#Aryl hydrocarbon receptor Effects on gastric acid secretion D01XNB DB00339 Pyrazinamide small molecule approved 98-96-4 123.1127 C5H5N3O Pyrazinamide kills or stops the growth of certain bacteria that cause tuberculosis (TB). It is used with other drugs to treat tuberculosis. It is a highly specific agent and is active only against Mycobacterium tuberculosis. In vitro and in vivo, the drug is active only at a slightly acid pH. Pyrazinamie gets activated to Pyrazinoic acid in the bacilli where it interferes with fatty acid synthase FAS I. This interferes with the bacteriums ability to synthesize new fatty acids, required for growth and replication. D0XF8W DB00340 Metixene small molecule approved 4969-02-2 309.468 C20H23NS P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3 Metixene is a tertiary antimuscarinic with actions similar to those of atropine; it also has antihistaminic and direct antispasmodic properties. It is used for the symptomatic treatment of parkinsonism, including the alleviation of the extrapyramidal syndrome induced by other drugs such as phenothiazines, but, like other antimuscarinics, it is of no value against tardive dyskinesias. Metixene has been discontinued. D0NF0W DB00341 Cetirizine small molecule approved 83881-51-0 388.888 C21H25ClN2O3 P70174#Histamine H1 receptor General effects and respiratory effects D0DK8V DB00342 Terfenadine small molecule approved 50679-08-8 471.6734 C32H41NO2 P70174#Histamine H1 receptor@P20309#Muscarinic acetylcholine receptor M3@P11229#Muscarinic acetylcholine receptor M1@P08912#Muscarinic acetylcholine receptor M5@P08173#Muscarinic acetylcholine receptor M4@P08172#Muscarinic acetylcholine receptor M2@Q12809#Potassium voltage-gated channel subfamily H member 2 Terfenadine, an H1-receptor antagonist antihistamine, is similar in structure to astemizole and haloperidol, a butyrophenone antipsychotic. The active metabolite of terfenadine is fexofenadine. D08SOF DB00343 Diltiazem small molecule approved 42399-41-7 414.518 C22H26N2O4S Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q06432#Voltage-dependent calcium channel gamma-1 subunit Diltiazem is an antihypertensive and vasodilating agent that works by relaxing the vascular muscle and reducing blood pressure. This is related to the long-term therapeutic effects, as lowering the blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.12 Diltiazem inhibits the influx of extracellular calcium ions across the myocardial and vascular smooth muscle cell membranes during depolarization. Diltiazem is classified as a negative inotrope (decreased force) and negative chronotrope (decreased rate).9 It is also considered a rate-control drug as it reduces heart rate.2,8 Diltiazem is exerts hemodynamic actions by reducing blood pressure, systemic vascular resistance, the rate-pressure product, and coronary vascular resistance while increasing coronary blood flow.10 Diltiazem decreases sinoatrial and atrioventricular conduction in isolated tissues and has a negative inotropic effect in isolated preparations.12 In supraventricular tachycardia, diltiazem prolongs AV nodal refractories.10 D0OB1J DB00344 Protriptyline small molecule approved 438-60-8 263.3767 C19H21N P23975#Sodium-dependent noradrenaline transporter@P31645#Sodium-dependent serotonin transporter Protriptyline is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin by nerve cells. The effectiveness of antidepressants appear after approximately two weeks following recommended adminsitration schedule. Gradual changes are thought to occur in the cerebral cortex and hippocampus, involved in emotion regulation as part of the limbic system, as receptor sensitivity is enhanced. While α1 and β1 receptors are sensitized, α2 receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also reported to alter the perceptions of pain, including neuropathic or neuralgic pain, so they may exhibit analgesic properties. The mechanism of action behind this analgesic property is not fully understood; however, it is thought to involve modulation of endogenous opioid systems in the CNS via an indirect serotonergic route. Tricyclic antidepressants are also effective in relieving migraine prophylaxis, but not in abortion of acute migraine attack, potentially via their serotonergic effects. D00MYQ DB00345 Aminohippuric acid small molecule approved 61-78-9 194.1873 C9H10N2O3 Aminohippurate (p-aminohippuric acid, PAH, PAHA) is the glycine amide of p-aminobenzoic acid. It is filtered by the glomeruli and is actively secreted by the proximal tubules. At low plasma concentrations (1.0 to 2.0 mg/100 mL), an average of 90 percent of aminohippurate is cleared by the kidneys from the renal blood stream in a single circulation. It is ideally suited for measurement of ERPF since it has a high clearance, is essentially nontoxic at the plasma concentrations reached with recommended doses, and its analytical determination is relatively simple and accurate. Aminohippurate is also used to measure the functional capacity of the renal tubular secretory mechanism or transport maximum (TmPAH). This is accomplished by elevating the plasma concentration to levels (40-60 mg/100 mL) sufficient to saturate the maximal capacity of the tubular cells to secrete aminohippurate. Inulin clearance is generally measured during TmPAH determinations since glomerular filtration rate (GFR) must be known before calculations of secretory Tm measurements can be done. DB00346 Alfuzosin small molecule approved 81403-80-7 389.4488 C19H27N5O4 P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor By selectively inhibiting alpha adrenergic receptors in the lower urinary tract, alfuzosin causes smooth muscle relaxation in the bladder neck and prostate, improving urine flow, thereby reducing BPH symptoms.9 Additionally, alfuzosin reduces the vasoconstrictor effect of catecholamines (epinephrine and norepinephrine), leading to peripheral vasodilation.11 This leads to a risk of postural hypotension/syncope, and prescribing information warns that caution should be exercised in patients who take nitrates, antihypertensives, or have experienced decreased blood pressure after using other medications.9 D09MWJ DB00347 Trimethadione small molecule approved 127-48-0 143.1406 C6H9NO3 O43497#Voltage-dependent T-type calcium channel subunit alpha-1G Paramethadione and trimethadione are anticonvulsants indicated in the control of absence (petit mal) seizures that are refractory to treatment with other medications. Dione anticonvulsants are used in the treatment of epilepsy. They act on the central nervous system (CNS) to reduce the number of seizures. D0U4VT DB00348 Nitisinone small molecule approved 104206-65-7 329.2281 C14H10F3NO5 P32754#4-hydroxyphenylpyruvate dioxygenase Hereditary tyrosinemia type 1 occurs due to a deficiency in fumarylacetoacetase (FAH), the final enzyme in the tyrosine catabolic pathway. Nitisinone inhibits catabolism of tyrosine by preventing the catabolic intermediates. In patients with HT-1, these catabolic intermediates are converted to the toxic metabolites succinylacetone and succinylacetoacetate, which are responsible for the observed liver and kidney toxicity. Succinylacetone can also inhibit the porphyrin synthesis pathway leading to the accumulation of 5-aminolevulinate, a neurotoxin responsible for the porphyric crises characteristic of HT-1. D0V1UW DB00349 Clobazam small molecule approved 22316-47-8 300.74 C16H13ClN2O2 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Similar to other benzodiazepines, clobazam binds to the interface of the α and γ2-subunit of the GABA-A receptor. However, it is considered a partial agonist to GABA-A receptors which sets clobazam apart from 1,4-benzodiazepines which are full agonist. The significance of this difference is that one may experience less sedation with clobazam than with other benzodiazepines. Unlike the endogenous GABA ligand, clobazam binds allosterically to the GABA receptor to increase the frequency of the chloride channel opening and membrane permeability to chloride ions. Pharmacodynamic tolerance has been demonstrated in animal models. DB00350 Minoxidil small molecule approved 38304-91-5 209.2483 C9H15N5O P48048#ATP-sensitive inward rectifier potassium channel 1@P00797#Renin@P23219#Prostaglandin G/H synthase 1 Minoxidil is an orally effective direct acting peripheral vasodilator that reduces elevated systolic and diastolic blood pressure by decreasing peripheral vascular resistance. Minoxidil is also used topically to treat androgenetic alopecia. Microcirculatory blood flow in animals is enhanced or maintained in all systemic vascular beds. In man, forearm and renal vascular resistance decline; forearm blood flow increases while renal blood flow and glomerular filtration rate are preserved. The predominant site of minoxidil action is arterial. Venodilation does not occur with minoxidil; thus, postural hypotension is unusual with its administration. The antihypertensive activity of minoxidil is due to its sulphate metabolite, minoxidil sulfate. D0Y2CJ DB00351 Megestrol acetate small molecule approved 595-33-5 384.516 C24H32O4 P06401#Progesterone receptor@P04150#Glucocorticoid receptor Megestrol is a synthetic progestin and has the same physiologic effects as natural progesterone. These effects include induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. Mestrogel has slight glucocorticoid activity and very slight mineralocorticoid activity. This drug has no estrogenic, androgenic, or anabolic activity. The precise mechanism of megestrol’s antianorexic and anticachetic effects is unknown. Initially developed as a contraceptive, it was first evaluated in breast cancer treatment in 1967. DB00352 Tioguanine small molecule approved 154-42-7 167.192 C5H5N5S Thioguanine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Thioguanine was first synthesized and entered into clinical trial more than 30 years ago. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Thioguanine is cross-resistant with mercaptopurine. Cytotoxicity is cell cycle phase-specific (S-phase). DB00353 Methylergometrine small molecule approved 113-42-8 339.4314 C20H25N3O2 P21728#D(1A) dopamine receptor@P41595#5-hydroxytryptamine receptor 2B Methylergometrine is a semisynthetic ergot alkaloid and a derivative of ergonovine and is used for the prevention and control of postpartum and post-abortion hemorrhage. In general, the effects of all the ergot alkaloids appear to results from their actions as partial agonists or antagonists at adrenergic, dopaminergic, and tryptaminergic receptors. The spectrum of effects depends on the agent, dosage, species, tissue, and experimental or physiological conditions. All of the alkaloids of ergot significantly increase the motor activity of the uterus. After small doses contractions are increased in force or frequency, or both, but are followed by a normal degree of relaxation. As the dose is increased, contractions become more forceful and prolonged, resting tonus is markedly increased, and sustained contracture can result. DB00354 Buclizine small molecule approved 82-95-1 433.028 C28H33ClN2 P70174#Histamine H1 receptor@P11229#Muscarinic acetylcholine receptor M1 Buclizine is a piperazine-derivative antihistamine used as an antivertigo/antiemetic agent. Buclizine is used in the prevention and treatment of nausea, vomiting, and dizziness associated with motion sickness. Additionally, it has been used in the management of vertigo in diseases affecting the vestibular apparatus. Although the mechanism by which buclizine exerts its antiemetic and antivertigo effects has not been fully elucidated, its central anticholinergic properties are partially responsible. The drug depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone. It also possesses anticholinergic, antihistaminic, central nervous system depressant, and local anesthetic effects. D03XSJ DB00355 Aztreonam small molecule approved 78110-38-0 435.433 C13H17N5O8S2 Q93LQ9#Beta-lactamase Aztreonam is a monocyclic beta-lactam antibiotic (a monobactam) originally isolated from Chromobacterium violaceum. Aztreonam exhibits potent and specific activity in vitro against a wide spectrum of gram-negative aerobic pathogens including Pseudomonas aeruginosa. It has no useful activity against gram-positive bacteria or anaerobes, but has very broad spectrum against gram-negative aerobes, including Pseudomonas aeruginosa. This has given it the nickname "the magic bullet for aerobic gram-negative bacteria". Aztreonam, unlike the majority of beta-lactam antibiotics, does not induce beta-lactamase activity and its molecular structure confers a high degree of resistance to hydrolysis by beta-lactamases (such as penicillinases and cephalosporinases) produced by most gram-negative and gram-positive pathogens; it is, therefore, usually active against gram-negative aerobic microorganisms that are resistant to antibiotics hydrolyzed by beta-lactamases. It is active against many strains that are multiply-resistant to other antibiotics, such as certain cephalosporins, penicillin, and aminoglycosides. Aztreonam maintains its antimicrobial activity over a pH range of 6 to 8 in vitro, as well as in the presence of human serum and under anaerobic conditions. D0F2XV DB00356 Chlorzoxazone small molecule approved 95-25-0 169.565 C7H4ClNO2 Q12791#Calcium-activated potassium channel subunit alpha-1 Chlorzoxazone is a centrally-acting agent for painful musculoskeletal conditions. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex a.c. involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles. D08ZEB DB00357 Aminoglutethimide small molecule approved 125-84-8 232.2783 C13H16N2O2 P11511#Aromatase@P05108#Cholesterol side-chain cleavage enzyme, mitochondrial Aminoglutethimide inhibits the enzymatic conversion of cholesterol to D5-pregnenolone, resulting in a decrease in the production of adrenal glucocorticoids, mineralocorticoids, estrogens, and androgens. D0M6DO DB00358 Mefloquine small molecule approved 53230-10-7 378.3122 C17H16F6N2O P29274#Adenosine receptor A2a D0GQ7K DB00359 Sulfadiazine small molecule approved 68-35-9 250.277 C10H10N4O2S Q27738#Dihydropteroate synthetase Sulfadiazine is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus. D05LKP DB00360 Sapropterin small molecule approved 62989-33-7 241.2471 C9H15N5O3 P00439#Phenylalanine-4-hydroxylase@P29474#Nitric oxide synthase, endothelial@P07101#Tyrosine 3-monooxygenase@P17752#Tryptophan 5-hydroxylase 1 Tetrahydrobiopterin (BH4) is used to convert several amino acids, including phenylalanine, to other essential molecules in the body including neurotransmitters. Tetrahydrobiopterin deficiency can be caused by mutations in GTP cyclohydrolase 1 (GCH1), 6-pyruvoyl-tetrahydropterin synthase/dimerization cofactor of hepatocyte nuclear factor 1 alpha (PCBD1), 6-pyruvoyltetrahydropterin synthase (PTS), and quinoid dihydropteridine reductase (QDPR) genes. These genes make the enzymes that are critical for producing and recycling tetrahydrobiopterin. If one of the enzymes fails to function correctly because of a gene mutation, little or no tetrahydrobiopterin is produced. As a result, phenylalanine from the diet builds up in the bloodstream and other tissues and can damage nerve cells in the brain. High levels of phenylalanine can result in signs and symptoms ranging from temporary low muscle tone to mental retardation, movement disorders, difficulty swallowing, seizures, behavioral problems, progressive problems with development, and an inability to control body temperature. DB00361 Vinorelbine small molecule approved 71486-22-1 778.947 C45H54N4O8 Q7KQL5#Tubulin beta chain Vinorelbine is a semi-synthetic vinca-alkaloid with a wide spectrum of anti-tumor activity. The vinca-alkaloids are considered spindle poisons. They work by interfering with the polymerization of tubulin, a protein responsible for building the microtubule system which appears during cell division in proliferating cancer cells 11. D01HTL DB00362 Anidulafungin small molecule approved 166663-25-8 1140.2369 C58H73N7O17 Anidulafungin is a semi-synthetic lipopeptide synthesized from a fermentation product of Aspergillus nidulans. Anidulafungin is an echinocandin, a class of antifungal drugs that inhibits the synthesis of 1,3-β-D-glucan, an essential component of fungal cell walls. Anidulafungin is active in vitro against many Candida, as well as some Aspergillus. Like other echinocandins, anidulafungin is not active against Cryptococcus neoformans, Trichosporon, Fusarium, or zygomycetes. D0F9BY DB00363 Clozapine small molecule approved 5786-21-0 326.823 C18H19ClN4 P21728#D(1A) dopamine receptor@P20309#Muscarinic acetylcholine receptor M3@P08913#Alpha-2A adrenergic receptor@P35367#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor@P28222#5-hydroxytryptamine receptor 1B@P09211#Glutathione S-transferase P Clozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of clozapine. Clozapine's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Clozapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Clozapine's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug. D0Z1RV DB00364 Sucralfate small molecule approved 54182-58-0 1558.67 C12H35Al9O55S8 P01133#Pro-epidermal growth factor@P09038#Fibroblast growth factor 2@P02671#Fibrinogen alpha chain@P02675#Fibrinogen beta chain@P02679#Fibrinogen gamma chain This drug aids in the healing of duodenal ulcers, relieving painful inflammation by creating a protective mechanical barrier between the lining or skin of the gastrointestinal tract and damaging substances 2. In addition, sucralfate acts to increase levels of growth factors locally, and also causes an increase in prostaglandins which are important in the healing of the mucosa (lining) of the gastrointestinal tract 2. D06ULU DB00365 Grepafloxacin small molecule approved 119914-60-2 359.3947 C19H22FN3O3 Grepafloxacin has in vitro activity against a wide range of gram-positive and gram-negative aerobic microorganisms, as well as some atypical microorganisms. D0JL2K DB00366 Doxylamine small molecule approved 469-21-6 270.3694 C17H22N2O P35367#Histamine H1 receptor@Q14994#Nuclear receptor subfamily 1 group I member 3@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3 Doxylamine is an antihistamine commonly used as a sleep aid. This drug is also used to relieve symptoms of hay fever (allergic rhinitis), hives (rash or itching), and other allergic reactions. Doxylamine is a member of the ethanolamine class of antihistamines and has anti-allergy power far superior to virtually every other antihistamine on the market, with the exception of diphenhydramine (Benadryl). It is also the most powerful over-the-counter sedative available in the United States, and more sedating than many prescription hypnotics. In a study, it was found to be superior to even the barbiturate, phenobarbital for use as a sedative. Doxylamine is also a potent anticholinergic. D0Y2LR DB00367 Levonorgestrel small molecule approved 797-63-7 312.4458 C21H28O2 P06401#Progesterone receptor@P18405#3-oxo-5-alpha-steroid 4-dehydrogenase 1@P10275#Androgen receptor@P04278#Sex hormone-binding globulin@P04150#Glucocorticoid receptor Levonorgestrel prevents pregnancy by interfering with ovulation, fertilization, and implantation. The levonorgestrel-only containing emergency contraceptive tablet is 89% effective if it is used according to prescribing information within 72 hours after intercourse.3,7 The intrauterine and implantable devices releasing levonorgestrel are more than 99% in preventing pregnancy.14,21,22 Levonorgestrel utilized as a component of hormonal therapy helps to prevent endometrial carcinoma associated with unopposed estrogen administration.13 D0BA9U DB00368 Norepinephrine small molecule approved 51-41-2 169.1778 C8H11NO3 P08588#Beta-1 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P07550#Beta-2 adrenergic receptor@P00439#Phenylalanine-4-hydroxylase@P13945#Beta-3 adrenergic receptor Noradrenaline acts on both alpha-1 and alpha-2 adrenergic receptors to cause vasoconstriction. Its effect in-vitro is often limited to the increasing of blood pressure through antagonising alpha-1 and alpha-2 receptors and causing a resultant increase in systemic vascular resistance. D07MOX DB00369 Cidofovir small molecule approved 113852-37-2 279.187 C8H14N3O6P P09252#DNA polymerase catalytic subunit Cidofovir is a new anti-viral drug. It is classified as a nucleotide analogue and is active against herpes cytomegalovirus (CMV) retinitis infection. Most adults are infected with CMV. Cidofovir suppresses cytomegalovirus (CMV) replication by selective inhibition of viral DNA synthesis. D04AAW DB00370 Mirtazapine small molecule approved 85650-52-8 265.3529 C17H19N3 P28223#5-hydroxytryptamine receptor 2A@Q9UE69#5HT3 serotonin receptor@P08913#Alpha-2A adrenergic receptor@P28335#5-hydroxytryptamine receptor 2C@P41145#Kappa-type opioid receptor@P70174#Histamine H1 receptor General effects and a note on suicidality D05ZIK DB00371 Meprobamate small molecule approved 57-53-4 218.2502 C9H18N2O4 P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P47869#Gamma-aminobutyric acid receptor subunit alpha-2@P34903#Gamma-aminobutyric acid receptor subunit alpha-3@P48169#Gamma-aminobutyric acid receptor subunit alpha-4@P31644#Gamma-aminobutyric acid receptor subunit alpha-5@Q16445#Gamma-aminobutyric acid receptor subunit alpha-6 Meprobamate is an anxiolytic drug. It was the best selling minor tranquilizer for a time but has largely been replaced by benzodiazepines. Meprobamate has most of the pharmacological effects and dangers of the barbiturates (though it was marketed as being safer) but it is less sedating at effective doses. Meprobamate exhibits some anticonvulsant effects in absence seizures; however, it is reported to potentially exacerbate generalized tonic-clonic seizures. It has also been used as a hypnotic (sleeping pill). However, its is currently only licensed as an anxiolytic and it is a third or fourth-order choice. D0Y4AW DB00372 Thiethylperazine small molecule approved 1420-55-9 399.616 C22H29N3S2 P14416#D(2) dopamine receptor Thiethylperazine, an atypical antipsychotic agent, is used to treat both negative and positive symptoms of schizophrenia, acute mania with bipolar disorder, agitation, and psychotic symptoms in dementia. Future uses may include the treatment of obsessive-compulsive disorder and severe behavioral disorders in autism. Structurally and pharmacologically similar to clozapine, Thiethylperazine binds to alpha(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors. D0Y0ER DB00373 Timolol small molecule approved 26839-75-8 316.42 C13H24N4O3S P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@Q37875#Lysozyme Timolol, when administered by the ophthalmic route, rapidly reduces intraocular pressure. When administered in the tablet form, it reduces blood pressure, heart rate, and cardiac output, and decreases sympathetic activity.1,2,3,17. This drug has a fast onset of action, usually occurring within 20 minutes of the administration of an ophthalmic dose. Timolol maleate can exert pharmacological actions for as long as 24 hours if given in the 0.5% or 0.25% doses.23 D05UVD DB00374 Treprostinil small molecule approved 81846-19-7 390.5131 C23H34O5 P43119#Prostacyclin receptor@P43116#Prostaglandin E2 receptor EP2 subtype@Q13258#Prostaglandin D2 receptor@Q03181#Peroxisome proliferator-activated receptor delta@Q9H244#P2Y purinoceptor 12 As an analogue of prostacyclin, treprostinil promotes the vasodilation of pulmonary and systemic arterial vascular beds and the inhibition of platelet aggregation 5,6,7. In animals, the vasodilatory effects of treprostinil lead to a reduction of right and left ventricular afterload and an increase in cardiac output and stroke volume.6 Treprostinil also causes a dose-related negative inotropic and lusitropic effect, and no major effects on cardiac conduction have been detected.6 Short-lasting effects on QTc were detected in healthy volunteers (n=240) given inhaled single doses of 54 and 84 μg of treprostinil. These effects dissipated rapidly as treprostinil concentrations lowered.5 When given subcutaneously or intravenously, treprostinil has the potential to reach higher concentrations.6 The effect of oral treprostinil on QTc has not been evaluated.7 D01WUA DB00376 Trihexyphenidyl small molecule approved 144-11-6 301.4662 C20H31NO P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5 Trihexyphenidyl is an antimuscarinic indicated as an adjunct in the treatment of parkinsonism or as a treatment for drug-induced extrapyramidal symptoms.11,12 It has a long duration of action as it does not need to be given every day.13 It has a wide therapeutic window, with acute toxicity being non fatal in doses as high as 300 mg.13 Patients should have their iridocorneal angle examined before and intraocular pressure monitored during therapy.13 Patients should be counselled regarding the risk of anhidrosis and hyperthermia.13 D09GFL DB00377 Palonosetron small molecule approved 135729-56-5 296.414 C19H24N2O P46098#5-hydroxytryptamine receptor 3A Palonosetron is an antinauseant and antiemetic agent indicated for the prevention of nausea and vomiting associated with moderately-emetogenic cancer chemotherapy and for the prevention of postoperative nausea and vomiting. Palonosetron is a highly specific and selective serotonin 5-HT3 receptor antagonist that is pharmacologically related to other 5-HT3 receptor antagonists, but differs structurally. Palonosetron has a high affinity for 5-HT3 receptors, but has little to no affinity for other receptors. The serontonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. It is suggested that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting. D04FVU DB00378 Dydrogesterone small molecule approved 152-62-5 312.4458 C21H28O2 P06401#Progesterone receptor Dydrogesterone is an orally active progestogen which acts directly on the uterus, producing a complete secretory endometrium in an estrogen-primed uterus. At therapeutic levels, dydrogesterone has no contraceptive effect as it does not inhibit or interfere with ovulation or the corpus luteum. Furthermore, dydrogesterone is non-androgenic, non-estrogenic, non-corticoid, non-anabolic and is not excreted as pregnanediol. Dydrogesterone helps to regulate the healthy growth and normal shedding of the uterus lining. Therefore, it may be useful in the treatment of menstrual disorders such as absent, irregular or painful menstrual periods, infertility, premenstrual syndrome and endometriosis. D0F1UL DB00379 Mexiletine small molecule approved 31828-71-4 179.2588 C11H17NO Q14524#Sodium channel protein type 5 subunit alpha@P35869#Aryl hydrocarbon receptor Mexiletine is a local anesthetic, antiarrhythmic agent (Class Ib), structurally similar to lidocaine, but orally active. Mexiletine has fast onset and offset kinetics, meaning that they have little or no effect at slower heart rates, and more effects at faster heart rates. It shortens the action potential duration, reduces refractoriness, and decreases Vmax in partially depolarized cells with fast response action potentials. Mexiletine either does not change the action potential duration, or decreases the action potential duration. D0X0RI DB00380 Dexrazoxane small molecule approved 24584-09-6 268.2691 C11H16N4O4 P11388#DNA topoisomerase 2-alpha@Q02880#DNA topoisomerase 2-beta Dexrazoxane is a cardioprotective agent for use in conjunction with doxorubicin indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose. Patients receiving anthracycline-derivative antineoplastic agents may experience three types of cardiotoxicity: acute transient type; chronic, subacute type (related to cumulative dose and has a more indolent onset later on); and a late-onset type that manifests years after therapy, mainly in patients that have been exposed to the drug as a child. Although the exact mechanism of anthracycline-induced cardiotoxicity is not known, it has shown to exert a variety of actions that may result in the development of cardiotoxicity. In animals, anthracyclines cause a selective inhibition of cardiac muscle gene expression for α-actin, troponin, myosin light-chain 2, and the M isoform of creatine kinase. This may lead to myofibrillar loss associated with anthracycline-induced cardiotoxicity. Anthracyclines may also cause myocyte damage via calcium overload, altered myocardial adrenergic function, release of vasoactive amines, and proinflammatory cytokines. Furthermore, it has been suggested that the main cause of anthracycline-induced cardiotoxicity is associated with free-radical damage to DNA. The drugs intercalate DNA, chelate metal ions to produce drug-metal complexes, and generate superoxide radicals via oxidation-reduction reactions. Anthracyclines also contain a quinone structure that can undergo reduction via NADPH-dependent reactions to produce a semiquinone free radical that initiates a cascade of superoxide and hydroxide radical generation. Chelation of metal ions, particularly iron, by anthracyclines results in an anthracycline-metal complex that catalyzes the generation of reactive oxygen free radicals. This complex is a powerful oxidant that can initiate lipid peroxidation in the absence of oxygen free radicals. The toxicity induced by antrhacyclines may be exacerbated in cardiac cells, as these cells do not possess sufficient amounts of certain enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) involved in detoxifying free radicals and protecting the cells from subsequent damage. D07XVN DB00381 Amlodipine small molecule approved 88150-42-9 408.876 C20H25ClN2O5 Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q9P0X4#Voltage-dependent T-type calcium channel subunit alpha-1I@Q00975#Voltage-dependent N-type calcium channel subunit alpha-1B@Q02641#Voltage-dependent L-type calcium channel subunit beta-1@Q8IZS8#Voltage-dependent calcium channel subunit alpha-2/delta-3@P00915#Carbonic anhydrase 1@P17405#Sphingomyelin phosphodiesterase General pharmacodynamic effects D08JIV DB00382 Tacrine small molecule approved 321-64-2 198.2637 C13H14N2 P06276#Cholinesterase@P22303#Acetylcholinesterase@P23141#Liver carboxylesterase 1 Tacrine is a parasympathomimetic- a reversible cholinesterase inhibitor that is indicated for the treatment of mild to moderate dementia of the Alzheimer's type. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. Tacrine is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine at cholinergic synapses through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, tacrine's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact. There is no evidence that tacrine alters the course of the underlying dementing process. D0E6YQ DB00383 Oxyphencyclimine small molecule approved 125-53-1 344.4479 C20H28N2O3 P20309#Muscarinic acetylcholine receptor M3@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2 Oxyphencyclimine is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract. Oxyphencyclimine is an antimuscarinic, anticholinergic drug. D0H5DU DB00384 Triamterene small molecule approved 396-01-0 253.2626 C12H11N7 P51170#Amiloride-sensitive sodium channel subunit gamma@P37088#Amiloride-sensitive sodium channel subunit alpha@P51168#Amiloride-sensitive sodium channel subunit beta@P51172#Amiloride-sensitive sodium channel subunit delta Triamterene, a relatively weak, potassium-sparing diuretic and antihypertensive, is used in the management of hypertension and edema. It primarily works on the distal nephron in the kidneys; it acts from the late distal tubule to the collecting duct to inhibit Na+ reabsorption and decreasing K+ excretion.11 As triamterene tends to conserve potassium more strongly than promoting Na+ excretion, it can cause an increase in serum potassium, which may result in hyperkalemia potentially associated with cardiac irregularities.15 In healthy volunteers administered with oral triamterene, there was an increase in the renal clearnace of sodium and magnesium, and a decrease in the clearance of uric acid and creatinine5 due to its effect of reducing glomerular filtration renal plasma flow.13 Triamterene does not affect calcium excretion.13 In clinical trials, the use of triamterene in combination with hydrochlorothiazide resulted an enhanced blood pressure-lowering effects of hydrochlorothiazide.7 D00NKB DB00385 Valrubicin small molecule approved 56124-62-0 723.651 C34H36F3NO13 P11388#DNA topoisomerase 2-alpha Valrubicin is an anticancer agent. D07IPB DB00387 Procyclidine small molecule approved 77-37-2 287.4397 C19H29NO P20309#Muscarinic acetylcholine receptor M3@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P08173#Muscarinic acetylcholine receptor M4 Procyclidine has an atropine-like action on parasympathetic-innervated peripheral structures including smooth muscle. It's antispasmodic effects are thought to be related to the blockage of central cholinergic receptors M1, M2 and M4. It is used to treat symptomatic Parkinsonism and extrapyramidal dysfunction caused by antipsychotic agents. D0R1WR DB00388 Phenylephrine small molecule approved 59-42-7 167.205 C9H13NO2 P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor Phenylephrine is an alpha-1 adrenergic agonist that raises blood pressure,6,8 dilates the pupils,7 and causes local vasoconstriction.1 Ophthalmic formulations of phenylephrine act for 3-8 hours7 while intravenous solutions have an effective half life of 5 minutes and an elimination half life of 2.5 hours.3,6 Patients taking ophthalmic formulations of phenylephrine should be counselled about the risk of arrhythmia, hypertension, and rebound miosis.7 Patients taking an intravenous formulation should be counselled regarding the risk of bradycardia, allergic reactions, extravasation causing necrosis or tissue sloughing, and the concomitant use of oxytocic drugs.6,8 D0O6IU DB00389 Carbimazole small molecule approved 22232-54-8 186.232 C7H10N2O2S P07202#Thyroid peroxidase Carbimazole is a carbethoxy derivative of methimazole. Its antithyroid action is due to its conversion to methimazole after absorption. It is used to treat hyperthyroidism and thyrotoxicosis. D02CKX DB00390 Digoxin small molecule approved 20830-75-5 780.9385 C41H64O14 P05023#Sodium/potassium-transporting ATPase subunit alpha-1 Digoxin is a positive inotropic and negative chronotropic drug7, meaning that it increases the force of the heartbeat and decreases the heart rate.23 The decrease in heart rate is particularly useful in cases of atrial fibrillation, a condition characterized by a fast and irregular heartbeat.13 The relief of heart failure symptoms during digoxin therapy has been demonstrated in clinical studies by increased exercise capacity and reduced hospitalization due to heart failure and reduced heart failure-related emergency medical visits.25 Digoxin has a narrow therapeutic window.25 D02OZE DB00391 Sulpiride small molecule approved 15676-16-1 341.426 C15H23N3O4S P00918#Carbonic anhydrase 2@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor@P07451#Carbonic anhydrase 3 Sulpiride is a substituted benzamide derivative and a selective dopamine D2 antagonist indicated to treat acute and chronic schizophrenia.6,7,8,10 It has a short duration of action as it is given twice daily, and a wide therapeutic window as patients have survived single doses as high as 16g.10 Patients should be counselled regarding increased motor agitation, extrapyramidal reactions, and neuroleptic malignant syndrome.10 D03QGM DB00392 Profenamine small molecule approved 522-00-9 312.472 C19H24N2S P11229#Muscarinic acetylcholine receptor M1@Q8TCU5#Glutamate receptor ionotropic, NMDA 3A@P08172#Muscarinic acetylcholine receptor M2 Ethopropazine, a phenothiazine and antidyskinetic, is used in the treatment of Parkinson's disease. By improving muscle control and reducing stiffness, this drug permits more normal movements of the body as the disease symptoms are reduced. It is also used to control severe reactions to certain medicines such as reserpine, phenothiazines, chlorprothixene, thiothixene, loxapine, and haloperidol. Unlike other NMDA antagonists, ethopropazine — because of its anticholinergic action — is largely devoid of neurotoxic side effects. Ethopropazine also has a slight antihistaminic and local anesthetic effect. DB00393 Nimodipine small molecule approved 66085-59-4 418.4403 C21H26N2O7 Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@O60840#Voltage-dependent L-type calcium channel subunit alpha-1F@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@Q02641#Voltage-dependent L-type calcium channel subunit beta-1@Q08289#Voltage-dependent L-type calcium channel subunit beta-2@P54284#Voltage-dependent L-type calcium channel subunit beta-3@O00305#Voltage-dependent L-type calcium channel subunit beta-4@P08235#Mineralocorticoid receptor@P35869#Aryl hydrocarbon receptor Nimodipine belongs to the class of pharmacological agents known as calcium channel blockers. Nimodipine is indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured congenital aneurysms who are in good neurological condition post-ictus (e.g., Hunt and Hess Grades I-III). The contractile processes of smooth muscle cells are dependent upon calcium ions, which enter these cells during depolarization as slow ionic transmembrane currents. Nimodipine inhibits calcium ion transfer into these cells and thus inhibits contractions of vascular smooth muscle. In animal experiments, nimodipine had a greater effect on cerebral arteries than on arteries elsewhere in the body perhaps because it is highly lipophilic, allowing it to cross the blood brain barrier. D0XN1F DB00394 Beclomethasone dipropionate small molecule approved 5534-09-8 521.042 C28H37ClO7 P04150#Glucocorticoid receptor Inflammatory conditions, including asthma, dermatoses, and allergic rhinitis, involve the activation of cascades by inflammatory mediators. Inflammation is a primary defense mechanism and the homeostatic response of the immune system; however, a prolonged inflammatory response in certain disorders may lead to tissue damage, pain, and swelling. Beclomethasone dipropionate works by attenuating the inflammatory responses associated with asthma, allergic rhinitis, nasal polyps, and corticosteroid-responsive dermatoses. It suppresses the actions of inflammatory cells, such as mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils. It also inhibits the release of inflammatory mediators, such as histamine, eicosanoids, leukotrienes, and cytokines.11 Beclomethasone dipropionate is reported to exhibit potent topical activity while possessing low systemic effects.2 DB00395 Carisoprodol small molecule approved 78-44-4 260.33 C12H24N2O4 P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P47870#Gamma-aminobutyric acid receptor subunit beta-2@P18507#Gamma-aminobutyric acid receptor subunit gamma-2@P31644#Gamma-aminobutyric acid receptor subunit alpha-5@P34903#Gamma-aminobutyric acid receptor subunit alpha-3 Carisoprodol is a centrally acting skeletal muscle relaxant that does not act directly on skeletal muscle but acts directly on the central nervous system (CNS). This drug relieves the painful effects of muscle spasm 12,19. A metabolite of carisoprodol, meprobamate, possesses both anxiolytic and sedative properties Label. Clinical studies have shown that this drug causes impairment of psychomotor performance in neuropsychological tests.5,10 D05PLH DB00396 Progesterone small molecule approved 57-83-0 314.4617 C21H30O2 P03372#Estrogen receptor@P10275#Androgen receptor@P05093#Steroid 17-alpha-hydroxylase/17,20 lyase@P06401#Progesterone receptor@P41145#Kappa-type opioid receptor@P08235#Mineralocorticoid receptor@P04278#Sex hormone-binding globulin@Q92731#Estrogen receptor beta@P04150#Glucocorticoid receptor@P02763#Alpha-1-acid glycoprotein 1 Progesterone, depending on concentration and dosage form, and timing of exposure may have several pharmacodynamic effects. These actions, according, to various preparations, are listed below: D07BSQ DB00397 Phenylpropanolamine small molecule approved 14838-15-4 151.209 C9H13NO P21728#D(1A) dopamine receptor@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Phenylpropanolamine (PPA), a sympathomimetic agent structurally similar to pseudoephedrine, is used to treat nasal congestion. Phenylpropanolamine is found in appetite suppressant formulations and with guaifenesinin in cough-cold formulations. In 2000, the FDA requested that all drug companies discontinue marketing products containing phenylpropanolamine, due to an increased risk of hemorrhagic stroke in women who used phenylpropanolamine. D09JXM DB00398 Sorafenib small molecule approved 284461-73-0 464.825 C21H16ClF3N4O3 P35916#Vascular endothelial growth factor receptor 3@P17948#Vascular endothelial growth factor receptor 1@P04049#RAF proto-oncogene serine/threonine-protein kinase@P36888#Receptor-type tyrosine-protein kinase FLT3@P09619#Platelet-derived growth factor receptor beta@P35968#Vascular endothelial growth factor receptor 2@P10721#Mast/stem cell growth factor receptor Kit@P15056#Serine/threonine-protein kinase B-raf@P11362#Fibroblast growth factor receptor 1@P07949#Proto-oncogene tyrosine-protein kinase receptor Ret No large changes in QTc interval were observed. After one 28-day treatment cycle, the largest mean QTc interval change of 8.5 ms (upper bound of two-sided 90% confidence interval, 13.3 ms) was observed at 6 hours post-dose on day 1 of cycle 2. D0W5HK DB00399 Zoledronic acid small molecule approved 118072-93-8 272.0896 C5H10N2O7P2 O95749#Geranylgeranyl pyrophosphate synthase@P14324#Farnesyl pyrophosphate synthase Zoledronic acid is a third generation, nitrogen containing bisphosphonate that inhibits osteoclast function and prevents bone resorption.5 The therapeutic window is wide as patients are unlikely to suffer severe effects from overdoses and the duration of action is long.14,15,16 Patients should be counselled regarding the risk of electrolyte deficiencies, renal impairment, osteonecrosis of the jaw, atypical femoral fractures, bronchoconstriction, hepatic impairment, hypocalcemia, and embryo-fetal toxicity.14,15,16 DB00400 Griseofulvin small molecule approved 126-07-8 352.766 C17H17ClO6 Q7KQL5#Tubulin beta chain@Q99456#Keratin, type I cytoskeletal 12 Griseofulvin is a mycotoxic metabolic product of Penicillium spp. It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than forty years. Griseofulvin is fungistatic with in vitro activity against various species of Microsporum Epidermophyton, and Trichophyton. It has no effect on bacteria or on other genera of fungi. Following oral administration, griseofulvin is deposited in the keratin precursor cells and has a greater affinity for diseased tissue. The drug is tightly bound to the new keratin which becomes highly resistant to fungal invasions. Once the keratin-Griseofulvin complex reaches the skin site of action, it binds to fungal microtubules (tubulin) thus altering fungal mitosis. D0C1SF DB00401 Nisoldipine small molecule approved 63675-72-9 388.4144 C20H24N2O6 Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@P54289#Voltage-dependent calcium channel subunit alpha-2/delta-1@Q08289#Voltage-dependent L-type calcium channel subunit beta-2@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S Nisoldipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nisoldipine is similar to other peripheral vasodilators. Nisoldipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. D0S5CU DB00402 Eszopiclone small molecule approved 138729-47-2 388.808 C17H17ClN6O3 P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P47869#Gamma-aminobutyric acid receptor subunit alpha-2@P34903#Gamma-aminobutyric acid receptor subunit alpha-3@P31644#Gamma-aminobutyric acid receptor subunit alpha-5 Eszopiclone rapidly induces sleep and decreases sleep latency. It also aids in the maintenance of sleep, preventing frequent awakenings.3,4,10 This drug has shown anticonvulsant and muscle relaxant properties in animals but is used in humans for its sedating effects.9 D06ZII DB00403 Ceruletide small molecule approved 17650-98-5 1352.405 C58H73N13O21S2 P32238#Cholecystokinin receptor type A Caerulein is a specific decapeptide similar in action and composition to the natural gastrointestinal peptide hormone cholecystokinin that stimulates gastric, biliary, and pancreatic secretion. It also exerts stimulatory actions on certain smooth muscles. D0Y9TS DB00404 Alprazolam small molecule approved 28981-97-7 308.765 C17H13ClN4 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Alprazolam is a benzodiazepine that binds γ-aminobutyric acid (GABA) type-A receptors (GABAARs) to enhance their inhibitory effect on neurotransmission, specifically in the brain.18,19 Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death; patients taking benzodiazepines and opioids concurrently may require lower doses of one or both medications, depending on their clinical situation. Patients with pre-existing impaired respiratory function are at increased risk of adverse effects including death during treatment with benzodiazepines. In addition, due to its CNS depressant effects, patients taking alprazolam should avoid operating heavy machinery or driving and should avoid other CNS depressants such as alcohol. As with other benzodiazepines, alprazolam carries a risk of abuse, misuse, and addiction, which is higher in predisposed individuals and may require strict monitoring. Cessation of therapy may result in acute or protracted withdrawal symptoms, which may be life-threatening; the patient dose should be gradually tapered whenever discontinuation or reduced dosage are necessary. Newborns born to mothers using alprazolam later in pregnancy may suffer from sedation and withdrawal symptoms. As CYP3A is required for the initial step in alprazolam metabolism, alprazolam is contraindicated in patients taking strong CYP3A inhibitors, such as ketoconazole and itraconazole; milder CYP3A inhibitors still necessitate alprazolam dosage adjustments. Lastly, benzodiazepines may have negative effects, such as panic disorders, increased suicide incidence, and episodes of mania/hypomania, in patients suffering from depression.4,7,18,19 D0L9GG DB00405 Dexbrompheniramine small molecule approved 132-21-8 319.239 C16H19BrN2 P70174#Histamine H1 receptor In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Dexbrompheniramine is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. D02WIW DB00406 Gentian violet cation small molecule approved 7438-46-2 372.5258 C25H30N3 Gentian violet is a mutagen, a mitotic poison, and a clastogen. Gentian violet has been used in medicine for almost 100 years: as an antiseptic for external use, as a topical antibiotic, as a topical antifungal agent, as an antihelminthic agent by oral administration, and more recently, as a blood additive to prevent transmission of Chagas' disease. It is thought to work by binding to the DNA of target organisms and causing disruption, mutation or inhibition of DNA replication. DB00408 Loxapine small molecule approved 1977-10-2 327.808 C18H18ClN3O P14416#D(2) dopamine receptor Loxapine, a dibenzoxazepine compound, represents a subclass of tricyclic antipsychotic agents, chemically distinct from the thioxanthenes, butyrophenones, and phenothiazines. Pharmacologically, Loxapine is a tranquilizer for which the exact mode of action has not been established, however, it is believed that by antagonising dopamine and serotonin receptors, there is a marked cortical inhibition which can manifest as tranquilization and suppression of aggression. D0U5OE DB00409 Remoxipride small molecule approved 80125-14-0 371.269 C16H23BrN2O3 P28223#5-hydroxytryptamine receptor 2A@Q99720#Sigma non-opioid intracellular receptor 1 Remoxipride is a weak selective dopamine D2 receptor antagonist that was once used in the treatment of schizophrenia.1 It has a moderate therapeutic index and duration of action.8 Remoxipride was withdrawn due to deaths associated with aplastic anemia.5 D01PIL DB00410 Mupirocin small molecule approved 12650-69-0 500.6222 C26H44O9 P41972#Isoleucine--tRNA ligase Mupirocin is reported to be active against susceptible aerobic gram-positive cocci, such as Staphylococcus aureus, Staphylococcus epidermidis, and other beta-hemolytic streptococciStreptococcus pyogenes.4 It mediates its antibacterial activity by inhibiting the bacterial protein synthesis and formation of bacterial proteins essential for survival. The minimum bactericidal concentration (MBC) against relevant pathogens is generally eight-fold to thirty-fold higher than the minimum inhibitory concentration (MIC).7 In one clinical study investigating the therapeutic effectiveness of topical mupirocin in impetigo, the therapeutic response rate was about 94 to 98% after one week following the end of therapy.7 In clinical studies of patients with primary and secondary skin infections, both elimination of the bacterial pathogen and clinical cure or improvement hav been demonstrated in over 90% of patients receiving topical mupirocin.3 Mupirocin resistance as high as 81% has been reported previously.5 Resistance to mupirocin, which occurs more frequently in methicillin-resistant than methicillin-susceptible staphylococci, may occur with the production of a modified isoleucyl-tRNA synthetase, or the acquisition of, by genetic transfer, a plasmid mediating a new isoleucyl-tRNA synthetase.7 D03JSJ DB00411 Carbamoylcholine small molecule approved 462-58-8 147.1955 C6H15N2O2 P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@Q15822#Neuronal acetylcholine receptor subunit alpha-2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4 Carbamoylcholine is a parasympathomimetic that acts as an agonist of muscarinic and nicotinic receptors.3,9 It is more resistant to hydrolysis by acetylcholinesterase than other choline esters leading to a longer duration of action, with significant effects 24 hours after administration.5 Data regarding the therapeutic index of carbamoylcholine is not readily available.9 Patients should be counselled regarding the risk of administering the drug to patients with acute cardiac failure, bronchial asthma, peptic ulcer, hyperthyroidism, gastrointestinal spasm, urinary tract obstruction, or Parkinson's disease.9 DB00412 Rosiglitazone small molecule approved 122320-73-4 357.427 C18H19N3O3S P37231#Peroxisome proliferator-activated receptor gamma@O60488#Long-chain-fatty-acid--CoA ligase 4@Q07869#Peroxisome proliferator-activated receptor alpha@Q03181#Peroxisome proliferator-activated receptor delta@P19793#Retinoic acid receptor RXR-alpha@P28702#Retinoic acid receptor RXR-beta@P48443#Retinoic acid receptor RXR-gamma When rosiglitazone is used as monotherapy, it is associated with increases in total cholesterol, LDL, and HDL. It is also associated with decreases in free fatty acids. Increases in LDL occurred primarily during the first 1 to 2 months of therapy with AVANDIA and LDL levels remained elevated above baseline throughout the trials. In contrast, HDL continued to rise over time. As a result, the LDL/HDL ratio peaked after 2 months of therapy and then appeared to decrease over time. DB03310 Glutathione disulfide small molecule approved 27025-41-8 612.631 C20H32N6O12S2 Q6NSD4#Glutathione peroxidase@P10620#Microsomal glutathione S-transferase 1@P28161#Glutathione S-transferase Mu 2@P00390#Glutathione reductase, mitochondrial Not Available DB03312 Brivudine small molecule approved 69304-47-8 333.135 C11H13BrN2O5 O00142#Thymidine kinase 2, mitochondrial@P0DOO6#DNA polymerase@P13159#Thymidine kinase Not Available DB03585 Oxyphenbutazone small molecule approved 129-20-4 324.3737 C19H20N2O3 Q9NZK7#Group IIE secretory phospholipase A2 Not Available D06ZPS DB03614 Mecobalamin small molecule approved 13422-55-4 1344.3823 C63H91CoN13O14P Q99707#Methionine synthase Not Available D09ZHZ DB03615 Ribostamycin small molecule approved 25546-65-0 454.4727 C17H34N4O10 P0A7S3#30S ribosomal protein S12@P07237#Protein disulfide-isomerase@P9WQG9#Aminoglycoside 2'-N-acetyltransferase@Q9R381#Aminoglycoside N(6')-acetyltransferase type 1 Not Available D08PVY DB03619 Deoxycholic acid small molecule approved 83-44-3 392.572 C24H40O4 P09211#Glutathione S-transferase P@P07445#Steroid Delta-isomerase@P54965#Choloylglycine hydrolase@Q96RI1#Bile acid receptor@P31224#Multidrug efflux pump subunit AcrB@Q8GGK7#Cytochrome C@Q7Z2Z2#Elongation factor Tu GTP-binding domain-containing protein 1@P25553#Lactaldehyde dehydrogenase@P33517#Cytochrome c oxidase subunit 1@Q03736#Cytochrome c oxidase subunit 2 Not Available DB03754 Tromethamine small molecule approved 77-86-1 121.135 C4H11NO3 P05067#Amyloid beta A4 protein Not Available D03ZFN DB03756 Doconexent small molecule approved 6217-54-5 328.4883 C22H32O2 Q07869#Peroxisome proliferator-activated receptor alpha@P37231#Peroxisome proliferator-activated receptor gamma@P19793#Retinoic acid receptor RXR-alpha@P28702#Retinoic acid receptor RXR-beta@P48443#Retinoic acid receptor RXR-gamma@P36956#Sterol regulatory element-binding protein 1@P01106#Myc proto-oncogene protein DHA in the central nervous system is found in the phospholipid bilayers where it modulates the physical environment and increase the free volume within the membrane bilayer. It influences the G-protein coupled receptor activity and affects transmembrane transport and cell interaction with the exterior world. It is also reported to promote apoptosis, neuronal differentiation and ion channel activity. Like other polyunsaturated fatty acids, DHA acts as a ligand at PPARs that plays an anti-inflammatory effect and regulate inflammatory gene expression and NFκB activation. DHA also gives rise to resolvins and related compounds (e.g., protectins) through pathways involving cyclooxygenase and lipoxygenase enzymes to resolve the inflammatory responses. DB03766 Propanoic acid small molecule approved 79-09-4 74.0785 C3H6O2 P10724#Alanine racemase@Q9NQX3#Gephyrin@P96965#2-hydroxy-6-oxo-7-methylocta-2,4-dienoate hydrolase As a naturally occurring carboxylic acid, propionic acid typically undergoes metabolism via conversion to propionyl coenzyme A (propionyl-CoA), which is part of the usual metabolic pathway that carboxylic acids participate within in the human body 2,7. Most of propionic acid's antibacterial and preservative activities subsequently stem from this metabolic pathway as the metabolic fate of propionates varies in different microorganisms, resulting in antimicrobial mechanisms of action that may revolve around differing propionate metabolites causing competition, inhibition, and/or interference effects along other metabolic pathways in the various microorganisms affected 7. DB03793 Benzoic acid small molecule approved 65-85-0 122.123 C7H6O2 Q9L9D7#Cocaine esterase@O67987#Chlorocatechol 1,2-dioxygenase@P96965#2-hydroxy-6-oxo-7-methylocta-2,4-dienoate hydrolase@Q01234#Oxygen-insensitive NAD(P)H nitroreductase@O31168#Non-heme chloroperoxidase@Q5PXQ6#Hydroxyquinol 1,2-dioxygenase@Q52546#Replication protein@P14920#D-amino-acid oxidase Not Available DB03796 Palmitic Acid small molecule approved 57-10-3 256.4241 C16H32O2 P00709#Alpha-lactalbumin@Q07869#Peroxisome proliferator-activated receptor alpha@P08100#Rhodopsin@P50897#Palmitoyl-protein thioesterase 1@P02689#Myelin P2 protein@P09466#Glycodelin@Q14541#Hepatocyte nuclear factor 4-gamma@P83812#Lipid binding protein@P10632#Cytochrome P450 2C8@O43617#Trafficking protein particle complex subunit 3 Palmitic acid is the first fatty acid produced during lipogenesis (fatty acid synthesis) and from which longer fatty acids can be produced. Palmitate negatively feeds back on acetyl-CoA carboxylase (ACC) which is responsible for converting acetyl-ACP to malonyl-ACP on the growing acyl chain, thus preventing further palmitate generation DB03843 Formaldehyde small molecule approved 50-00-0 30.026 CH2O P15555#D-alanyl-D-alanine carboxypeptidase Not Available D01KEE DB03904 Urea small molecule approved 57-13-6 60.0553 CH4N2O P00378#Dihydrofolate reductase@P05089#Arginase-1@P00918#Carbonic anhydrase 2@P35222#Catenin beta-1@Q8XB74#Sulfoxide reductase catalytic subunit YedY Urea is a keratolytic emollient that works to treat or prevent dry, rough, scaly, itchy skin.1 D02XBW DB03929 D-Serine small molecule approved 312-84-5 105.0926 C3H7NO3 Q05586#Glutamate receptor ionotropic, NMDA 1@P23415#Glycine receptor subunit alpha-1@P29508#Serpin B3@P36275#Head decoration protein Not Available D02UDJ DB04038 Ergosterol small molecule approved 57-87-4 396.659 C28H44O Not Available DB04115 Berberine small molecule approved 2086-83-1 336.3612 C20H18NO4 O15392#Baculoviral IAP repeat-containing protein 5@P0A0N4#HTH-type transcriptional regulator QacR Not Available D0W8WB DB04160 Pyrophosphoric acid small molecule approved 2466-09-3 177.9751 H4O7P2 P22939#Farnesyl diphosphate synthase Not Available DB04173 Fructose small molecule approved 180.1559 C6H12O6 P02943#Maltoporin Not Available D06HZY DB04209 Dequalinium small molecule approved 6707-58-0 456.6654 C30H40N4 P98170#E3 ubiquitin-protein ligase XIAP@P29973#cGMP-gated cation channel alpha-1@Q12791#Calcium-activated potassium channel subunit alpha-1@P0A0N4#HTH-type transcriptional regulator QacR@P0DP23#Calmodulin@Q9UGI6#Small conductance calcium-activated potassium channel protein 3@P37840#Alpha-synuclein In vitro, dequalinium possesses antimicrobial activity against gram-positive and gram-negative bacteria, yeasts, and protozoa.6 Dequalinium has a rapid bactericidal and fungicidal action.1 The antiparasitic and antiviral properties of dequalinium have also been noted. For example, dequalinium can bind to the membrane-proximal external region (MPER) of the spike envelope of the human immunodeficiency virus HIV-1.9 DB04221 Didecyldimethylammonium small molecule approved 20256-56-8 326.6232 C22H48N P9WPB5#Cyclopropane mycolic acid synthase 2 Not Available DB04224 Oleic Acid small molecule approved 112-80-1 282.4614 C18H34O2 Q07869#Peroxisome proliferator-activated receptor alpha@Q03181#Peroxisome proliferator-activated receptor delta@P19793#Retinoic acid receptor RXR-alpha@P37231#Peroxisome proliferator-activated receptor gamma@P02689#Myelin P2 protein Not Available DB04272 Citric acid small molecule approved 77-92-9 192.1235 C6H8O7 P15121#Aldose reductase@P00808#Beta-lactamase@P39126#Isocitrate dehydrogenase [NADP]@C7C422#Metallo-beta-lactamase type 2 Not Available DB04339 Carbocisteine small molecule approved 638-23-3 179.194 C5H9NO4S Q63HM9#PI-PLC X domain-containing protein 3@Q9UNP4#Lactosylceramide alpha-2,3-sialyltransferase Due to its mucolytic effects, carbocisteine significantly reduces sputum viscosity, cough, dyspnea and fatigue.1,2 Additionally, it prevents pulmonary infections by decreasing accumulated mucus in the respiratory tract; this is especially beneficial in preventing exacerbations of COPD caused by bacteria and viruses.2 It has in-vitro anti-inflammatory activity with some demonstrated action against free radicals.2 D0X5SI DB04348 Taurocholic acid small molecule approved 81-24-3 515.703 C26H45NO7S P19835#Bile salt-activated lipase@Q96RI1#Bile acid receptor@P51161#Gastrotropin Not Available DB00413 Pramipexole small molecule approved 104632-26-0 211.327 C10H17N3S P08913#Alpha-2A adrenergic receptor@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor Parkinson's Disease D0G8NN DB00414 Acetohexamide small molecule approved 968-81-0 324.395 C15H20N2O4S P48048#ATP-sensitive inward rectifier potassium channel 1 Acetohexamide is an intermediate-acting, first-generation oral sulfonylurea. It lowers blood sugar by stimulating the pancreatic beta cells to secrete insulin and by helping the body use insulin efficiently. Due to its primary action on the pancreatic beta cells, the drug is only effective when there are functional pancreatic beta cells that can produce insulin granules. Acetohexamide has one-third the potency of chlorpropamide, and twice the potency of tolbutamide; however, similar hypoglycemic efficacy occurs with equipotent dosage of sulfonylureas. D07WFK DB00415 Ampicillin small molecule approved 69-53-4 349.405 C16H19N3O4S A0A0E1R3H3#Penicillin-binding protein 3@P46059#Solute carrier family 15 member 1@Q16348#Solute carrier family 15 member 2@Q02763#Angiopoietin-1 receptor Ampicillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Ampicillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Ampicillin results from the inhibition of cell wall synthesis and is mediated through Ampicillin binding to penicillin binding proteins (PBPs). Ampicillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. D0YA9Z DB00416 Metocurine iodide small molecule approved 7601-55-0 906.6279 C40H48I2N2O6 Q15822#Neuronal acetylcholine receptor subunit alpha-2 Metocurine iodide is a benzylisoquinolinium competitive nondepolarizing neuromuscular blocking agent. Metocurine iodide has a moderate risk of inducing histamine release and has some ganglion blocking activity. Metocurine iodide can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored to assess degree of muscle relaxation. As with other nondepolarizing neuromuscular blockers, the time to onset of paralysis decreases and the duration of maximum effect increases with increasing doses of metocurine iodide. Repeated administration of maintenance doses of metocurine iodide has no cumulative effect on the duration of neuromuscular block if recovery is allowed to begin prior to repeat dosing. Moreover, the time needed to recover from repeat doses does not change with additional doses. Repeat doses can therefore be administered at relatively regular intervals with predictable results. DB00417 Phenoxymethylpenicillin small molecule approved 87-08-1 350.39 C16H18N2O5S P24228#D-alanyl-D-alanine carboxypeptidase DacB@P12256#Penicillin acylase DB00418 Secobarbital small molecule approved 76-73-3 238.2829 C12H18N2O3 P47869#Gamma-aminobutyric acid receptor subunit alpha-2@P34903#Gamma-aminobutyric acid receptor subunit alpha-3@P48169#Gamma-aminobutyric acid receptor subunit alpha-4@P31644#Gamma-aminobutyric acid receptor subunit alpha-5@Q16445#Gamma-aminobutyric acid receptor subunit alpha-6@P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P43681#Neuronal acetylcholine receptor subunit alpha-4@P36544#Neuronal acetylcholine receptor subunit alpha-7@P42262#Glutamate receptor 2@Q13002#Glutamate receptor ionotropic, kainate 2 Secobarbital, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation. D00SJE DB00419 Miglustat small molecule approved 72599-27-0 219.278 C10H21NO4 Q16739#Ceramide glucosyltransferase Miglustat, an N-alkylated imino sugar, is a synthetic analogue of D-glucose. Miglustat is an inhibitor of the enzyme glucosylceramide synthase, which is a glucosyl transferase enzyme responsible for catalyzing the formation of glucosylceramide (glucocerebroside). Glucosylceramide is a substrate for the endogenous glucocerebrosidase, an enzyme that is deficient in Gaucher's disease. The accumulation of glucosylceramide due to the absence of glucocerebrosidase results in the storage of this material in the lysosomes of tissue macrophages, leading to widespread pathology due to infiltration of lipid-engorged macrophages in the viscera, lymph nodes, and bone marrow. This results in secondary hematologic consequences including sever anemia and thrombocytopenia, in addition to the characteristic progressive hepatosplenomegaly, as well as skeletal complications including osteonecrosis and osteopenia with secondary pathological fractures. D0HR8Z DB00420 Promazine small molecule approved 58-40-2 284.419 C17H20N2S P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P35348#Alpha-1A adrenergic receptor@P11229#Muscarinic acetylcholine receptor M1@P70174#Histamine H1 receptor Promazine belongs to a group of medications known as the phenothiazine antipsychotics. It acts by blocking a variety of receptors in the brain, particularly dopamine receptors. Dopamine is involved in transmitting signals between brain cells. When there is an excess amount of dopamine in the brain it causes over-stimulation of dopamine receptors. These receptors normally act to modify behaviour and over-stimulation may result in psychotic illness. Promazine hydrochloride blocks these receptors and stops them becoming over-stimulated, thereby helping to control psychotic illness. Promazine has weak extrapyramidal and autonomic side effects which lead to its use in the elderly, for restless or psychotic patients. Its anti-psychotic effect is also weaker and it is not useful in general psychiatry. D00NAX DB00421 Spironolactone small molecule approved 52-01-7 416.573 C24H32O4S P08235#Mineralocorticoid receptor@P10275#Androgen receptor@P06401#Progesterone receptor@P04150#Glucocorticoid receptor@P19099#Cytochrome P450 11B2, mitochondrial@P05093#Steroid 17-alpha-hydroxylase/17,20 lyase@P04278#Sex hormone-binding globulin@O75469#Nuclear receptor subfamily 1 group I member 2 Originally spironolactone was only studied for its potassium sparing diuretic effect.8 Spironolactone competitively inhibits mineralocorticoid receptors in the distal convoluted tubule to promote sodium and water excretion and potassium retention.8. Inhibition of this receptor leads to increased renin and aldosterone levels.8 D0EP0C DB00422 Methylphenidate small molecule approved 113-45-1 233.3062 C14H19NO2 D02PPN DB00423 Methocarbamol small molecule approved 532-03-6 241.2405 C11H15NO5 P00915#Carbonic anhydrase 1 Methacarbamol is a skeletal muscle relaxant with an unknown mechanism of action.5 Methacarbamol has been shown to block spinal polysynaptic reflexes, decrease nerve transmission in spinal and supraspinal polysynaptic pathways, and prolong the refractory period of muscle cells.5,4 Methocarbamol does not act as a local anesthetic upon injection.4 In animal studies, methocarbamol also prevents convulsions after electric shock.5 D0FN7J DB00424 Hyoscyamine small molecule approved 101-31-5 289.3694 C17H23NO3 P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@Q08828#Adenylate cyclase type 1 Hyoscyamine is not FDA approved, and so it has not official indications.7,8 However, it is used as an antimuscarinic agent in a number of treatments and therapies.7,8 Hyoscyamine has a short duration of action as it may need to be given multiple times per day.7,8 Patients should be counselled regarding the risks and signs of anticholinergic toxicity.7,8 D0RD5W DB00425 Zolpidem small molecule approved 82626-48-0 307.3895 C19H21N3O P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P47869#Gamma-aminobutyric acid receptor subunit alpha-2@P34903#Gamma-aminobutyric acid receptor subunit alpha-3@P18507#Gamma-aminobutyric acid receptor subunit gamma-2 Effects on the central nervous system (CNS) D0T1WN DB00426 Famciclovir small molecule approved 104227-87-4 321.3318 C14H19N5O4 P09252#DNA polymerase catalytic subunit Famciclovir is a prodrug that undergoes rapid biotransformation to the active antiviral compound penciclovir. Penciclovir is an anti-viral drug which has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). Therefore, herpes viral DNA synthesis and replication are selectively inhibited. D0VT8P DB00427 Triprolidine small molecule approved 486-12-4 278.3914 C19H22N2 P70174#Histamine H1 receptor In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Triprolidine, is a histamine H1 antagonist that competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. Triprolidine has anticholinergic and sedative effects. D0E8CI DB00428 Streptozocin small molecule approved 18883-66-4 265.2206 C8H15N3O7 Q89ZI2#O-GlcNAcase BT_4395@O60502#Protein O-GlcNAcase Streptozocin is an antitumour antibiotic consisting of a nitrosourea moiety interposed between a methyl group and a glucosamine. Streptozocin is indicated in the treatment of metastatic islet cell carcinoma of the pancreas. Streptozocin inhibits DNA synthesis in bacterial and mammalian cells. In bacterial cells, a specific interaction with cytosine moieties leads to degradation of DNA. The biochemical mechanism leading to mammalian cell death has not been definitely established; streptozocin inhibits cell proliferation at a considerably lower level than that needed to inhibit precursor incorporation into DNA or to inhibit several of the enzymes involved in DNA synthesis. Although streptozocin inhibits the progression of cells into mitosis, no specific phase of the cell cycle is particularly sensitive to its lethal effects. D0I8RR DB00429 Carboprost tromethamine small molecule approved 58551-69-2 489.6426 C25H47NO8 P34995#Prostaglandin E2 receptor EP1 subtype Carboprost tromethamine administered intramuscularly stimulates in the gravid uterus myometrial contractions similar to labor contractions at the end of a full term pregnancy. Whether or not these contractions result from a direct effect of carboprost on the myome-trium has not been determined. Nonetheless, they evacuate the products of conception from the uterus in most cases. Postpartum, the resultant myometrial contractions provide hemostasis at the site of placentation. Carboprost tromethamine also stimulates the smooth muscle of the human gastrointestinal tract. This activity may produce the vomiting or diarrhea or both that is common when carbo-prost tromethamine is used to terminate pregnancy and for use postpartum. In laboratory animals and also in humans carboprost tromethamine can elevate body temperature. With the clinical doses of carboprost trometh-amine used for the termination of pregnancy, and for use postpartum, some patients do experience transient temperature increases. In laboratory animals and in humans large doses of carboprost tromethamine can raise blood pressure, probably by contracting the vascular smooth muscle. With the doses of carboprost tromethamine used for terminating pregnancy, this effect has not been clinically significant. In laboratory animals and also in humans carboprost tromethamine can elevate body temperature. With the clinical doses of carboprost tromethamine used for the termination of pregnancy, some patients do experience temperature increases. In some patients, carboprost tromethamine may cause transient bronchoconstriction. DB00430 Cefpiramide small molecule approved 70797-11-4 612.637 C25H24N8O7S2 P02919#Penicillin-binding protein 1B@P08506#D-alanyl-D-alanine carboxypeptidase DacC@Q07806#Penicillin-binding protein 1A Cefpiramide is a cephalosporin active against Pseudomonas aeruginosa. It has a broad spectrum of antibacterial activity. Cefpiramide works by inhibiting bacterial cell wall biosynthesis. The plasma half-lives of cefpiramide in rabbits, dogs, and rhesus monkeys were much longer than those of cefoperazone and cefazolin. D02MZY DB00431 Lindane small molecule approved 58-89-9 290.83 C6H6Cl6 P18505#Gamma-aminobutyric acid receptor subunit beta-1@P23415#Glycine receptor subunit alpha-1@P23416#Glycine receptor subunit alpha-2@O75311#Glycine receptor subunit alpha-3@P48167#Glycine receptor subunit beta@P28472#Gamma-aminobutyric acid receptor subunit beta-3@P24046#Gamma-aminobutyric acid receptor subunit rho-1@P06401#Progesterone receptor@O75469#Nuclear receptor subfamily 1 group I member 2 Scabies is a common, highly pruritic infestation of the skin caused by Sarcoptes scabiei (lice). It is a very contagious condition with specific lesions, such as burrows, and nonspecific lesions, such as papules, vesicles and excoriations. The typical areas of the body it affects are finger webs, scalp (hair), wrists, axillary folds, abdomen, buttocks, inframammary folds and genitalia (males). It is characterized by intense night-time itching. Scabies is spread through close personal contact (relatives, sexual partners, schoolchildren, chronically ill patients and crowded communities). Scabies infestations and the corresponding symptoms can be eliminated by killing the scabies with topical insecticides or scabicides. Lindane is a scabicide that is essentially an organochloride insecticide. D0Q5IN DB00432 Trifluridine small molecule approved 70-00-8 296.1999 C10H11F3N2O5 P04818#Thymidylate synthase Trifluridine exhibits an antiviral effect against herpes simplex virus, types 1 and 2 and vacciniavirus both in vitro and in vivo 1. Some strains of adenovirus that contribute to the pathology of keratoconjunctivitis were shown to be susceptible to trifluridine in vitro 1. While there is evidence from a study that cross-resistance may develop between trifluridine and idoxuridine or vidarabine, trifluridine was shown to effective in treating dendritic ulcers in patients with herpetic keratitis who are unresponsive to idoxuridine or vidarabine based on the results from masked comparative trials 1. In nonclinical studies, trifluridine/tipiracil hydrochloride demonstrated antitumour activity against both 5-fluorouracil (5-FU) sensitive and resistant colorectal cancer cell lines 6. The cytotoxic activity of trifluridine and tipiracil against several human tumour xenografts show high correlation with the amount of trifluridine incorporated into DNA, indicating that the primary mechanism of action of trifluridine involves the direct incorporation into the cancer cell DNA 6. Trifluridine and tipiracil demonstrated anti-tumor activity against KRAS wild-type and mutant human colorectal cancer xenografts in mice Label. D05RHI DB00433 Prochlorperazine small molecule approved 58-38-8 373.943 C20H24ClN3S P35367#Histamine H1 receptor@P14416#D(2) dopamine receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Prochlorperazine is an antipsychotic agent that works to promote postsynaptic inhibition of dopaminergic neurons.10 It also exerts its anti-emetic actions via anti-dopaminergic effects, where it displays similar efficacy as ondansteron, a 5HT-3 receptor antagonist and anti-emetic, in preventing delayed nausea and vomiting.3 Prochlorperazine was shown to inhibit histaminergic, cholinergic and alpha-1 adrenergic receptors.1,9 The blockade of alpha-1 adrenergic receptors may result in sedation, muscle relaxation, and hypotension. It displays anti-anxiety effects as well.10 Compared to other phenothiazine derivatives, prochlorperazine is less sedating and has a weak propensity for causing hypotension or potentiating the effects of CNS depressants and anesthetics.12 Other than its primary action on D2 receptors, one study showed that prochlorperazine may inhibit the P2X7 receptor in human macrophages, leading to inhibition of calcium ion influx.9 D0B2UZ DB00434 Cyproheptadine small molecule approved 129-03-3 287.3981 C21H21N P70174#Histamine H1 receptor@P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P25021#Histamine H2 receptor@P41595#5-hydroxytryptamine receptor 2B@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P34969#5-hydroxytryptamine receptor 7 Cyproheptadine has been observed to antagonize several pharmacodynamic effects of serotonin in laboratory animals, including bronchoconstriction and vasodepression, and has demonstrated similar efficacy in antagonizing histamine-mediated effects.9 The reason for its efficacy in preventing anaphylactic shock has not been elucidated, but appears to be related to its anti-serotonergic effects.9 D00TLN DB00435 Nitric Oxide small molecule approved 10102-43-9 30.0061 NO P33402#Guanylate cyclase soluble subunit alpha-2@P04731#Metallothionein-1A@P14902#Indoleamine 2,3-dioxygenase 1@P29474#Nitric oxide synthase, endothelial Persistent pulmonary hypertension of the newborn (PPHN) occurs as a primary developmental defect or as a condition secondary to other diseases such as meconium aspiration syndrome (MAS), pneumonia, sepsis, hyaline membrane disease, congenital diaphragmatic hernia (CDH), and pulmonary hypoplasia. In these states, pulmonary vascular resistance (PVR) is high, which results in hypoxemia secondary to right-to-left shunting of blood through the patent ductus arteriosus and foramen ovale. In neonates with PPHN, Nitric oxide improves oxygenation (as indicated by significant increases in PaO2). Nitric oxide appears to increase the partial pressure of arterial oxygen (PaO2) by dilating pulmonary vessels in better entilated areas of the lung, redistributing pulmonary blood flow away from lung regions with low ventilation/perfusion (V/Q) ratios toward regions with normal ratios. D0A5FM DB00436 Bendroflumethiazide small molecule approved 73-48-3 421.415 C15H14F3N3O4S2 P55017#Solute carrier family 12 member 3@Q12791#Calcium-activated potassium channel subunit alpha-1@P00915#Carbonic anhydrase 1@P00918#Carbonic anhydrase 2@P22748#Carbonic anhydrase 4 Bendroflumethiazide, a thiazide diuretic, removes excess water from the body by increasing how often you urinate (pass water) and also widens the blood vessels which helps to reduce blood pressure. It inhibits Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. D02PAH DB00437 Allopurinol small molecule approved 315-30-0 136.1115 C5H4N4O P47989#Xanthine dehydrogenase/oxidase Allopurinol decreases the production of uric acid by stopping the biochemical reactions that precede its formation Label. This process decreases urate and relieves the symptoms of gout, which may include painful tophi, joint pain, inflammation, redness, decreased range of motion, and swelling 2. D04KYY DB00438 Ceftazidime small molecule approved 72558-82-8 546.576 C22H22N6O7S2 P02919#Penicillin-binding protein 1B Ceftazidime is a semisynthetic, broad-spectrum, third-generation cephalosporin antibiotic that is bactericidal through inhibition of enzymes responsible for cell-wall synthesis, primarily penicillin-binding protein 3 (PBP3).12 Among cephalosporins, ceftazidime is notable for its resistance to numerous β-lactamases and its broad spectrum of activity against Gram-negative bacteria, including Pseudomonas aeruginosa.4 However, it is less active than first- and second-generation cephalosporins against Staphylococcus aureus and other Gram-positive bacteria and also has low activity against anaerobes.4,9 Ceftazidime has confirmed activity against clinically relevant Gram-negative bacteria including Citrobacter spp., Enterobacter spp., Klebsiella spp., Proteus spp., Serratia spp., _Escherichia coli, Haemophilus influenzae, Neisseria meningitidis, Pseudomonas aeruginosa, and some Gram-positive bacteria including Staphylococcus spp. and Streptococcus spp. There are also in vitro data for ceftazidime efficacy against a wide variety of other bacteria, such as Acinetobacter baumannii and Neisseria gonorrhoeae, but no clear clinical studies to support the use of ceftazidime for infections caused by these bacteria.12 D0PH5Z DB00439 Cerivastatin small molecule approved 145599-86-6 459.5503 C26H34FNO5 P04035#3-hydroxy-3-methylglutaryl-coenzyme A reductase Cerivastatin, a competitive HMG-CoA reductase inhibitor effective in lowering LDL cholesterol and triglycerides, is used to treat primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb). D03KIA DB00440 Trimethoprim small molecule approved 738-70-5 290.3177 C14H18N4O3 P0ABQ4#Dihydrofolate reductase Trimethoprim exerts its antimicrobial effects by inhibiting an essential step in the synthesis of bacterial nucleic acids and proteins.14 It has shown activity against several species of gram-negative bacteria, as well as coagulase-negative Staphylococcus species. 14 Resistance to trimethoprim may arise via a variety of mechanisms, including alterations to the bacterial cell wall, overproduction of dihydrofolate reductase, or production of resistant dihydrofolate reductase.14 Rarely, trimethoprim can precipitate the development of blood disorders (e.g. thrombocytopenia, leukopenia, etc.) which may be preceded by symptoms such as sore throat, fever, pallor, and or purpura - patients should be monitored closely for the development of these symptoms throught the course of therapy.14 D0AO5H DB00441 Gemcitabine small molecule approved 95058-81-4 263.1981 C9H11F2N3O4 P23921#Ribonucleoside-diphosphate reductase large subunit@P04818#Thymidylate synthase@P30085#UMP-CMP kinase Gemcitabine is a nucleoside analog that mediates its antitumour effects by promoting apoptosis of malignant cells undergoing DNA synthesis. More specifically, it blocks the progression of cells through the G1/S-phase boundary.4 Gemcitabine demonstrated cytotoxic effects against a broad range of cancer cell lines in vitro. It displayed schedule-dependent antitumour activity in various animal models and xenografts from human non-small cell lung cancer (NSCLC) and pancreatic cancer.2 Therefore, the antineoplastic effects of gemcitabine are enhanced through prolonged infusion time rather than higher dosage.2 Gemcitabine inhibited the growth of human xenografts from carcinoma of the lung, pancreas, ovaries, head and neck, and breast. In mice, gemcitabine inhibited the growth of human tumour xenografts from the breast, colon, lung or pancreas by 69 to 99%. In clinical trials of advanced NSCLC, gemcitabine monotherapy produced objective response rates ranging from 18 to 26%, with a median duration of response ranging from 3.3 to 12.7 months. Overall median survival time was 6.2 to 12.3 months. The combined use of cisplatin and gemcitabine produced better objective response rates compared to monotherapy. In patients with advanced pancreatic cancer, objective response rates in patients ranged from 5.to 12%, with a median survival duration of 3.9 to 6.3 months.3 In Phase II trials involving patients with metastatic breast cancer, treatment with gemcitabine alone or with adjuvant chemotherapies resulted in response rate ranging from 13 to 42% and median survival duration ranging from 11.5 to 17.8 months. In metastatic bladder cancer, gemcitabine has a response rate 20 to 28%. In Phase II trials of advanced ovarian cancer, patients treated with gemcitabine had response rate of 57.1%, with progression free survival of 13.4 months and median survival of 24 months.2 D03UVS DB00442 Entecavir small molecule approved 142217-69-4 277.2792 C12H15N5O3 Entecavir is a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). It is designed to selectively inhibit the Hepatitis B virus, blocking all three steps in the replication process. Entecavir is more efficient than an older Hepatitis B drug, lamivudine. D0KR2J DB00443 Betamethasone small molecule approved 378-44-9 392.4611 C22H29FO5 P04150#Glucocorticoid receptor Corticosteroids bind to the glucocorticoid receptor inhibiting pro-inflammatory signals, while promoting anti-inflammatory signals.1 Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.1 Patients who require long-term treatment with a corticosteroid should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.1 D0CW1P DB00444 Teniposide small molecule approved 29767-20-2 656.654 C32H32O13S P11388#DNA topoisomerase 2-alpha Teniposide is a phase-specific cytotoxic drug, acting in the late S or early G 2 phase of the cell cycle. Teniposide prevents cell mitosis by causing single and double stranded DNA breaks as well as cross linking between protein and DNA. D01DBQ DB00445 Epirubicin small molecule approved 56420-45-2 543.5193 C27H29NO11 P11388#DNA topoisomerase 2-alpha Epirubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Epirubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Epirubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific. D0C9XJ DB00446 Chloramphenicol small molecule approved 56-75-7 323.129 C11H12Cl2N2O5 P08174#Complement decay-accelerating factor@P24093#Dr hemagglutinin structural subunit@P0ADY7#50S ribosomal protein L16 Chloramphenicol is a broad-spectrum antibiotic that was derived from the bacterium Streptomyces venezuelae and is now produced synthetically. Chloramphenicol is effective against a wide variety of microorganisms, but due to serious side-effects (e.g., damage to the bone marrow, including aplastic anemia) in humans, it is usually reserved for the treatment of serious and life-threatening infections (e.g., typhoid fever). Chloramphenicol is bacteriostatic but may be bactericidal in high concentrations or when used against highly susceptible organisms. Chloramphenicol stops bacterial growth by binding to the bacterial ribosome (blocking peptidyl transferase) and inhibiting protein synthesis. D0X6IU DB00447 Loracarbef small molecule approved 76470-66-1 349.769 C16H16ClN3O4 A0A0E1R3H3#Penicillin-binding protein 3 Loracarbef is considered a second generation cephalosporin antibiotic. The advantages of cephalosporin antibiotics include a broad range of activity, a safe record in children with almost no dose-related toxicity, and the lack of need to monitor levels. Adverse reactions are rare and consist primarily of hypersensitivity reactions with urticaria, nonspecific rash, and pruritus. Loracarbef can be used to treat a large number of bacterial infections caused by gram-negative and gram-positive bacteria, including upper respiratory tract bacterial infections, chronic bronchitis, pneumonia, sinusitis, pharyntitis and tonsillitis, skin absceses, urinary tract infections and pyelonephritis caused by E. coli, S. pyogenes, S. aureus, S. saprphyticus, S. penumoniae, H. influenzae and M. catarrhalis. D0E9WL DB00448 Lansoprazole small molecule approved 103577-45-3 369.361 C16H14F3N3O2S P20648#Potassium-transporting ATPase alpha chain 1@P10636#Microtubule-associated protein tau Lansoprazole decreases gastric acid secretion by targeting H+,K+-ATPase, which is the enzyme that catalyzes the final step in the acid secretion pathway in parietal cells. 6 Conveniently, lansoprazole administered any time of day is able to inhibit both daytime and nocturnal acid secretion.6 The result is that lansoprazole is effective at healing duodenal ulcers, reduces ulcer-related pain, and offers relief from symptoms of heartburn 6 Lansoprazole also reduces pepsin secretion, making it a useful treatment option for hypersecretory conditions such as Zollinger-Ellison syndrome.76 DB00449 Dipivefrin small molecule approved 52365-63-6 351.4373 C19H29NO5 P35348#Alpha-1A adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P07550#Beta-2 adrenergic receptor@P06276#Cholinesterase@P22303#Acetylcholinesterase Dipivefrin is a member of a class of drugs known as prodrugs. Prodrugs are usually not active in themselves and require biotransformation to the parent compound before therapeutic activity is seen. These modifications are undertaken to enhance absorption, decrease side effects and enhance stability and comfort, thus making the parent compound a more useful drug. Enhanced absorption makes the prodrug a more efficient delivery system for the parent drug because less drug will be needed to produce the desired therapeutic response. Dipivefrin is a prodrug of epinephrine formed by the diesterification of epinephrine and pivalic acid. The addition of pivaloyl groups to the epinephrine molecule enhances its lipophilic character and, as a consequence, its penetration into the anterior chamber. D01JFT DB00450 Droperidol small molecule approved 548-73-2 379.4274 C22H22FN3O2 P35348#Alpha-1A adrenergic receptor Droperidol produces marked tranquilization and sedation. It allays apprehension and provides a state of mental detachment and indifference while maintaining a state of reflex alertness. Droperidol produces an antiemetic effect as evidenced by the antagonism of apomorphine in dogs. It lowers the incidence of nausea and vomiting during surgical procedures and provides antiemetic protection in the postoperative period. Droperidol potentiates other CNS depressants. It produces mild alpha-adrenergic blockade, peripheral vascular dilatation and reduction of the pressor effect of epinephrine. It can produce hypotension and decreased peripheral vascular resistance and may decrease pulmonary arterial pressure (particularly if it is abnormally high). It may reduce the incidence of epinephrine-induced arrhythmias, but it does not prevent other cardiac arrhythmias. D03CJL DB00451 Levothyroxine small molecule approved 51-48-9 776.87 C15H11I4NO4 P06756#Integrin alpha-V@P05106#Integrin beta-3@P10827#Thyroid hormone receptor alpha@P10828#Thyroid hormone receptor beta Oral levothyroxine is a synthetic hormone that exerts the same physiologic effect as endogenous T4, thereby maintaining normal T4 levels when a deficiency is present. D06RGG DB00452 Framycetin small molecule approved 119-04-0 614.6437 C23H46N6O13 P0A7S3#30S ribosomal protein S12@P61073#C-X-C chemokine receptor type 4 Framycetin is used for the treatment of bacterial eye infections such as conjunctivitis. Framycetin is an antibiotic. It is not active against fungi, viruses and most kinds of anaerobic bacteria. Framycetin works by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Framycetin is useful primarily in infections involving aerobic bacteria bacteria. D05JNI DB00454 Meperidine small molecule approved 57-42-1 247.3327 C15H21NO2 Q05586#Glutamate receptor ionotropic, NMDA 1@Q13224#Glutamate receptor ionotropic, NMDA 2B@P41145#Kappa-type opioid receptor@Q12879#Glutamate receptor ionotropic, NMDA 2A@P23141#Liver carboxylesterase 1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3 Meperidine is a synthetic opiate agonist belonging to the phenylpiperidine class. Meperidine may produce less smooth muscle spasm, constipation, and depression of the cough reflex than equivalent doses of morphine. The onset of action is lightly more rapid than with morphine, and the duration of action is slightly shorter. The chemical structure of meperidine is similar to local anesthetics. Meperidine is recommended for relief of moderate to severe acute pain and has the unique ability to interrupt postoperative shivering and shaking chills induced by amphotericin B. Meperidine has also been used for intravenous regional anesthesia, peripheral nerve blocks and intraarticular, epidural and spinal analgesia. Meperidine is considered a second-line agent for the treatment of acute pain. D00UYE DB00455 Loratadine small molecule approved 79794-75-5 382.883 C22H23ClN2O2 P70174#Histamine H1 receptor@Q12809#Potassium voltage-gated channel subfamily H member 2 Like other 2nd generation antihistamines, loratadine is selective for peripheral H1 receptors.9 Loratadine does not penetrate effectively into the central nervous system and has poor affinity for CNS H1-receptors.9 These qualities result in a lack of CNS depressant effects such as drowsiness, sedation, and impaired psychomotor function.9 D06ABF DB00456 Cefalotin small molecule approved 153-61-7 396.438 C16H16N2O6S2 P15555#D-alanyl-D-alanine carboxypeptidase@P00811#Beta-lactamase@P0A3M6#Penicillin-binding protein 2B@Q8DR59#Penicillin-binding protein 1A@Q7CRA4#Penicillin-binding protein 1b Cefalotin (INN) or cephalothin (USAN) is a semisynthetic first generation cephalosporin having a broad spectrum of antibiotic activity that is administered parenterally. D01PLN DB00457 Prazosin small molecule approved 19216-56-9 383.4011 C19H21N5O4 P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor@Q12809#Potassium voltage-gated channel subfamily H member 2@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Effects on blood pressure D0WV3U DB00458 Imipramine small molecule approved 50-49-7 280.4073 C19H24N2 P20309#Muscarinic acetylcholine receptor M3@Q12809#Potassium voltage-gated channel subfamily H member 2@P35367#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2@P14416#D(2) dopamine receptor@Q9UK17#Potassium voltage-gated channel subfamily D member 3@P19652#Alpha-1-acid glycoprotein 2@P21728#D(1A) dopamine receptor Imipramine is a tricyclic antidepressant with general pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. While it acts to block both, imipramine displays a much higher affinity for the serotonin reuptake transporter than for the norepinephrine reuptake transporter 5. Imipramine produces effects similar to other monoamine targeting antidepressants, increasing serotonin- and norepinephrine-based neurotransmission. D06ZUK DB00459 Acitretin small molecule approved 55079-83-9 326.4293 C21H26O3 P19793#Retinoic acid receptor RXR-alpha@P10276#Retinoic acid receptor alpha@P10826#Retinoic acid receptor beta@P13631#Retinoic acid receptor gamma@P28702#Retinoic acid receptor RXR-beta@P48443#Retinoic acid receptor RXR-gamma@P09455#Retinol-binding protein 1 Acitretin is a retinoid. Retinoids have a structure similar to vitamin A and are involved in the normal growth of skin cells. Acitretin works by inhibiting the excessive cell growth and keratinisation (process by which skin cells become thickened due to the deposition of a protein within them) seen in psoriasis. It therefore reduces the thickening of the skin, plaque formation and scaling. D05QDC DB00460 Verteporfin small molecule approved 129497-78-5 718.7942 C41H42N4O8 Verteporfin, otherwise known as benzoporphyrin derivative, is a medication used in conjunction with laser treatment to eliminate the abnormal blood vessels in the eye associated with conditions such as the wet form of macular degeneration. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a wavelength of 693 nm in the presence of oxygen, produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to the endothelium and blockage of the vessels. D0I3XG DB00461 Nabumetone small molecule approved 42924-53-8 228.2863 C15H16O2 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 NSAIDs, like nabumetone, are well established as analgesics. NSAIDs reduce both peripheral and central sensitization of nociceptive neurons due to inflammation which contribute to hyperalgesia and allodynia.9,6 This sensitization occurs through reducing the action potential threshold in peripheral neurons, reducing the intensity of painful stimuli needed to produce a painful sensation. Centrally, activation of dorsal horn neurons occurs along with increased release of glutamate, calcitonin gene-related peptide (CGRP), and substance P which increase the transmission of painful stimuli. Coupled with this is an inhibition glycinergic neurons which normally inhibit pain transmission, a phenomenon known as disinhibition. Increased activity ofn-methyl d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors leads to the establishment of central sensitization, allowing both mild painful and innocuous stimuli to produce action potentials in nociceptive projection neurons. NSAIDs are effective in reducing mild-moderate acute and chronic nociceptive pain, however, the usefulness of NSAIDs in neuropathic pain is limited. D05CKR DB00462 Methscopolamine bromide small molecule approved 155-41-9 398.291 C18H24BrNO4 P08172#Muscarinic acetylcholine receptor M2@P11229#Muscarinic acetylcholine receptor M1@P20309#Muscarinic acetylcholine receptor M3 Methscopolamine is a muscarinic antagonist structurally similar to the neurotransmitter acetylcholine and acts by blocking the muscarinic acetylcholine receptors and is thus classified as an anticholinergic. Methscopolamine has many uses including the prevention of motion sickness. It is not clear how Methscopolamine prevents nausea and vomiting due to motion sickness. The vestibular part of the ear is very important for balance. When a person becomes disoriented due to motion, the vestibule sends a signal through nerves to the vomiting center in the brain, and vomiting occurs. Acetylcholine is a chemical that nerves use to transmit messages to each other. It is believe that Methscopolamine prevents communication between the nerves of the vestibule and the vomiting center in the brain by blocking the action of acetylcholine. Methscopolamine also may work directly on the vomiting center. Methscopolamine must be taken before the onset of motion sickness to be effective. DB00464 Sodium tetradecyl sulfate small molecule approved 139-88-8 316.43 C14H29NaO4S P07225#Vitamin K-dependent protein S@P04070#Vitamin K-dependent protein C Sodium tetradecyl sulfate is an anionic surfactant which occurs as a white, waxy solid. It is used as a sclerosing agent in sclerotherapy. Sclerotherapy is an injection of a sclerosing agent directly through the skin into a lesion and is used primarily for slow-flow vascular anomalies, particularly for venous malformation and lymphatic malformation. Intravenous injection causes intima inflammation and thrombus formation. This usually occludes the injected vein. Subsequent formation of fibrous tissue results in partial or complete vein obliteration that may or may not be permanent. DB00465 Ketorolac small molecule approved 74103-06-3 255.2686 C15H13NO3 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Ketorolac is a non-selective NSAID and acts by inhibiting both COX-1 and COX-2 enzymes which are normally responsible for converting arachidonic acid to prostaglandins. The COX-1 enzyme is constitutively active and can be found in platelets, gastric mucosa, and vascular endothelium. On the other hand, the COX-2 enzyme is inducible and mediates inflammation, pain and fever. D0D9JW DB00467 Enoxacin small molecule approved 74011-58-8 320.3189 C15H17FN4O3 P11388#DNA topoisomerase 2-alpha Enoxacin is a quinolone/fluoroquinolone antibiotic. Enoxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Enoxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. Enoxacin may be active against pathogens resistant to drugs that act by different mechanisms. D0R8ER DB00468 Quinine small molecule approved 130-95-0 324.4168 C20H24N2O2 P14770#Platelet glycoprotein IX@O15554#Intermediate conductance calcium-activated potassium channel protein 4 Quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. Quinine acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine. D03DDR DB00469 Tenoxicam small molecule approved 59804-37-4 337.37 C13H11N3O4S2 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Tenoxicam, an antiinflammatory agent with analgesic and antipyretic properties, is used to treat osteoarthritis and control acute pain. D0I6IB DB00470 Dronabinol small molecule approved 1972-08-3 314.4617 C21H30O2 P21554#Cannabinoid receptor 1@P34972#Cannabinoid receptor 2 DB00471 Montelukast small molecule approved 158966-92-8 586.183 C35H36ClNO3S Q9Y271#Cysteinyl leukotriene receptor 1@P09917#Arachidonate 5-lipoxygenase Montelukast is a leukotriene receptor antagonist that demonstrates a marked affinity and selectivity to the cysteinyl leukotriene receptor type-1 in preference to many other crucial airway receptors like the prostanoid, cholinergic, or beta-adrenergic receptors.3,4,5,6,7,8,9 As a consequence, the agent can elicit substantial blockage of LTD4 leukotriene-mediated bronchoconstriction with doses as low as 5 mg.3,4,5,6,7,8,9 Moreover, a placebo-controlled, crossover study (n=12) demonstrated that montelukast is capable of inhibiting early and late phase bronchoconstriction caused by antigen challenge by 75% and 57% respectively.3,4,5,6,7,8,9 D00QET DB00472 Fluoxetine small molecule approved 54910-89-3 309.3261 C17H18F3NO P31645#Sodium-dependent serotonin transporter@P28335#5-hydroxytryptamine receptor 2C@Q15822#Neuronal acetylcholine receptor subunit alpha-2@P32297#Neuronal acetylcholine receptor subunit alpha-3@P30926#Neuronal acetylcholine receptor subunit beta-4@P61024#Cyclin-dependent kinases regulatory subunit 1@Q12809#Potassium voltage-gated channel subfamily H member 2 Fluoxetine blocks the serotonin reuptake transporter in the presynaptic terminal, which ultimately results in sustained levels of 5-hydroxytryptamine (5-HT) in certain brain areas.13 However, fluoxetine binds with relatively poor affinity to 5-HT, dopaminergic, adrenergic, cholinergic, muscarinic, and histamine receptors which explains why it has a far more desirable adverse effect profile compared to earlier developed classes of antidepressants such as tricyclic antidepressants.132 D0TR5X DB00473 Hexylcaine small molecule approved 532-77-4 261.3593 C16H23NO2 Q14524#Sodium channel protein type 5 subunit alpha@Q9Y5Y9#Sodium channel protein type 10 subunit alpha Hexylcaine is a local ester-class anesthetic. Local anesthetics produce a transient block of nerve conduction by interfering with sodium channels. This effect of the anesthetic interferes with the development of an action potential across the nerve. D08MRN DB00474 Methohexital small molecule approved 151-83-7 262.3043 C14H18N2O3 P14867#Gamma-aminobutyric acid receptor subunit alpha-1 Methohexital, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation. D0S8TD DB00475 Chlordiazepoxide small molecule approved 58-25-3 299.755 C16H14ClN3O P28472#Gamma-aminobutyric acid receptor subunit beta-3 Chlordiazepoxide has antianxiety, sedative, appetite-stimulating and weak analgesic actions. The drug seems to block EEG arousal from stimulation in the brain stem reticular formation. The drug has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses. Hostile monkeys were made tame by oral drug doses which did not cause sedation. Chlordiazepoxide revealed a "taming" action with the elimination of fear and aggression. The taming effect of chlordiazepoxide was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals. D06BEP DB00476 Duloxetine small molecule approved 116539-59-4 297.415 C18H19NOS P31645#Sodium-dependent serotonin transporter@P23975#Sodium-dependent noradrenaline transporter@Q01959#Sodium-dependent dopamine transporter Duloxetine, through increasing serotonin and norepinephrine concentrations in Onuf's nucleus, enhances glutamatergic activation of the pudendal motor nerve which innervates the external urethral sphinter.9,10 This enhanced signaling allows for stronger contraction. Increased contraction of this sphincter increases the pressure needed to produce an incontinence episode in stress urinary incontinence. Duloxetine has been shown to improve Patient Global Impression of Improvement and Incontinence Quality of Life scores.11 It has also been shown to reduce the median incontinence episode frequency at doses of 40 and 80 mg. D01AXB DB00477 Chlorpromazine small molecule approved 50-53-3 318.864 C17H19ClN2S P21728#D(1A) dopamine receptor@P35367#Histamine H1 receptor@P14416#D(2) dopamine receptor Chlorpromazine is a psychotropic agent indicated for the treatment of schizophrenia. It also exerts sedative and antiemetic activity. Chlorpromazine has actions at all levels of the central nervous system-primarily at subcortical levels-as well as on multiple organ systems. Chlorpromazine has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity. D01ZII DB00478 Rimantadine small molecule approved 13392-28-4 179.3018 C12H21N Rimantadine, a cyclic amine, is a synthetic antiviral drug and a derivate of adamantane, like a similar drug amantadine. Rimantadine is inhibitory to the in vitro replication of influenza A virus isolates from each of the three antigenic subtypes (H1N1, H2H2 and H3N2) that have been isolated from man. Rimantadine has little or no activity against influenza B virus. Rimantadine does not appear to interfere with the immunogenicity of inactivated influenza A vaccine. D0TQ1G DB00479 Amikacin small molecule approved 37517-28-5 585.6025 C22H43N5O13 P0A7S3#30S ribosomal protein S12 Amikacin is an aminoglycoside antibiotic. Aminoglycosides bind to the bacteria, causing misreading of t-RNA, leaving bacteria unable to synthesize proteins vital to their growth. Aminoglycosides are useful mainly in the treatment infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, however, other antibiotics may be more potent and less toxic to humans.Label,6 D0Y3MO DB00480 Lenalidomide small molecule approved 191732-72-6 259.2606 C13H13N3O3 Q96SW2#Protein cereblon@O14788#Tumor necrosis factor ligand superfamily member 11@P33151#Cadherin-5@P35354#Prostaglandin G/H synthase 2 In hematological malignancies, the immune system is deregulated in the form of altered cytokine networks in the tumour microenvironment, defective T cell regulation of host-tumour immune interactions, and diminished NK cell activity.3 Lenalidomide is an immunomodulatory agent with antineoplastic, antiangiogenic, and anti-inflammatory properties.5 Lenalidomide exerts direct cytotoxicity by increasing apoptosis and inhibiting the proliferation of hematopoietic malignant cells.7 It delays tumour growth in nonclinical hematopoietic tumour models in vivo, including multiple myeloma.9 Lenalidomide also works to limit the invasion or metastasis of tumour cells and inhibits angiogenesis.7 D0Q5NX DB00481 Raloxifene small molecule approved 84449-90-1 473.583 C28H27NO4S P03372#Estrogen receptor@Q92731#Estrogen receptor beta@P04155#Trefoil factor 1 D01XBA DB00482 Celecoxib small molecule approved 169590-42-5 381.372 C17H14F3N3O2S P35354#Prostaglandin G/H synthase 2@P00918#Carbonic anhydrase 2@P07451#Carbonic anhydrase 3@H3BUU9#Cadherin-11@O15530#3-phosphoinositide-dependent protein kinase 1@Q99519#Sialidase-1 Celecoxib inhibits cyclooxygenase 2 (COX-2) enzyme, reducing pain and inflammation. It is important to note that though the risk of bleeding with celecoxib is lower than with certain other NSAIDS, it exists nonetheless and caution must be observed when it is administered to those with a high risk of gastrointestinal bleeding.28 D03RTS DB00483 Gallamine triethiodide small molecule approved 65-29-2 891.5291 C30H60I3N3O3 P08172#Muscarinic acetylcholine receptor M2@P22303#Acetylcholinesterase@Q15822#Neuronal acetylcholine receptor subunit alpha-2@P11229#Muscarinic acetylcholine receptor M1@P08912#Muscarinic acetylcholine receptor M5 Gallamine Triethiodide is a nondepolarizing neuromuscular blocking drug (NDMRD) used as an adjunct to anesthesia to induce skeletal muscle relaxation. The actions of gallamine triethiodide are similar to those of tubocurarine, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. Muscle groups differ in their sensitivity to these types of relaxants with ocular muscles (controlling eyelids) being most sensitive, followed by the muscles of the neck, jaw, limbs and then abdomen. The diaphragm is the least sensitive muscle to NDMRDs. Although the nondepolarizing neuromuscular blocking drugs do not have the same adverse effects as succinylcholine, their onset of action is slower. They also have a longer duration of action, making them more suitable for maintaining neuromuscular relaxation during major surgical procedures. DB00484 Brimonidine small molecule approved 59803-98-4 292.135 C11H10BrN5 P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P18825#Alpha-2C adrenergic receptor Brimonidine is a highly selective alpha-2 adrenergic receptor agonist that is 1000-fold more selective for the alpha2-adrenergic receptor than the alpha1-adrenergic receptor.15 This characteristic gives the drug some therapeutic advantages, since it reduces the risk of systemic side effects, such as systemic hypotension, bradycardia, and sedation. In addition, there is a reduction in the risk for developing alpha-1 mediated ocular unwanted effects, such as conjunctival blanching, mydriasis, and eyelid retraction.11 However, despite high alpha-2 receptor specificity, brimonidine may still produce alpha-1 adrenoceptor-mediated ocular effects, such as conjunctival vasoconstriction.6 Brimonidine has a peak ocular hypotensive effect occurring at two hours post-dosing.Label In a randomized, double-blind clinical study, ocular administration of 0.2% brimonidine in healthy volunteers resulted in a 23% reduction of mean intraocular pressure from baseline at 3 hours following administration.3 In comparative studies consisting of patients with open-angle glaucoma or ocular hypertension, the ocular hypotensive effect of brimonidine was maintained during treatment periods of up to 1 year.1 D0AE3X DB00485 Dicloxacillin small molecule approved 3116-76-5 470.326 C19H17Cl2N3O5S P0A3M6#Penicillin-binding protein 2B@Q8DR59#Penicillin-binding protein 1A@Q7CRA4#Penicillin-binding protein 1b Dicloxacillin is a beta-lactamase resistant penicillin similar to oxacillin. Dicloxacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of dicloxacillin results from the inhibition of cell wall synthesis and is mediated through dicloxacillin binding to penicillin binding proteins (PBPs). Dicloxacillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. D0R2KJ DB00486 Nabilone small molecule approved 51022-71-0 372.5408 C24H36O3 P21554#Cannabinoid receptor 1@P34972#Cannabinoid receptor 2 DB00487 Pefloxacin small molecule approved 70458-92-3 333.3574 C17H20FN3O3 P11388#DNA topoisomerase 2-alpha@Q06AK7#DNA topoisomerase 1 Pefloxacin is a fluoroquinolone antibiotic. Flouroquinolones such as pefloxacin possess excellent activity against gram-negative aerobic bacteria such as E.coli and Neisseria gonorrhoea as well as gram-positive bacteria including S. pneumoniae and Staphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter. D04NXQ DB00488 Altretamine small molecule approved 645-05-6 210.2794 C9H18N6 Altretamine is a novel antineoplastic agent. The precise mechanism by which altretamine exerts its cytotoxic effect is unknown, although a number of theoretical possibilities have been studied. Structurally, altretamine resembles the alkylating agent triethylenemelamine, yet in vitro tests for alkylating activity of altretamine and its metabolitics have been negative. Altretamine has been demonstrated to be efficacious for certain ovarian tumors resistant to classical alkylating agents. Metabolism of altretamine is a requirement of cytotoxicity. Synthetic monohydroxymethylmelamines, and products of altretamine metabolism, in vitro and in vivo, can form covalent adducts with tissue macromolecules including DNA, but the relevance of these reactions to antitumor activity is unknown. D02LPF DB00489 Sotalol small molecule approved 3930-20-9 272.364 C12H20N2O3S P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@Q12809#Potassium voltage-gated channel subfamily H member 2 Sotalol is a competitive inhibitor of the rapid potassium channel.2 This inhibition lengthens the duration of action potentials and the refractory period in the atria and ventricles.3,4 The inhibition of rapid potassium channels is increases as heart rate decreases, which is why adverse effects like torsades de points is more likely to be seen at lower heart rates.6 L-sotalol also has beta adrenergic receptor blocking activity seen above plasma concentrations of 800ng/L.6 The beta blocking ability of sotalol further prolongs action potentials.6 D-sotalol does not have beta blocking activity but also reduces a patient's heart rate while standing or exercising.6 These actions combine to produce a negative inotropic effect that reduces the strength of contractility of muscle cells in the heart.2 Extension of the QT interval is also adversely associated with the induction of arrhythmia in patients.4 D04VMT DB00490 Buspirone small molecule approved 36505-84-7 385.5031 C21H31N5O2 P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor D0U2OO DB00491 Miglitol small molecule approved 72432-03-2 207.2243 C8H17NO5 P10253#Lysosomal alpha-glucosidase@Q14697#Neutral alpha-glucosidase AB@Q8TET4#Neutral alpha-glucosidase C@O43451#Maltase-glucoamylase, intestinal Miglitol, an oral alpha-glucosidase inhibitor, is a desoxynojirimycin derivative that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. As a consequence of plasma glucose reduction, miglitol reduce levels of glycosylated hemoglobin in patients with Type II (non-insulin-dependent) diabetes mellitus. Systemic nonenzymatic protein glycosylation, as reflected by levels of glycosylated hemoglobin, is a function of average blood glucose concentration over time. Because its mechanism of action is different, the effect of miglitol to enhance glycemic control is additive to that of sulfonylureas when used in combination. In addition, miglitol diminishes the insulinotropic and weight-increasing effects of sulfonylureas. Miglitol has minor inhibitory activity against lactase and consequently, at the recommended doses, would not be expected to induce lactose intolerance. D0D0ZD DB00492 Fosinopril small molecule approved 98048-97-6 563.672 C30H46NO7P P12821#Angiotensin-converting enzyme Following oral administration, fosinopril is rapidly and completely hydrolyzed to its principle active metabolite, fosinoprilat. Hydrolysis is thought to occur in the gastrointestinal mucosa and liver. Fosinoprilat is a competitive inhibitor of ACE, a peptidyl dipeptidase that is part of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may further sustain the effects of fosinoprilat by causing increased vasodilation and decreased blood pressure. D0X8KY DB00493 Cefotaxime small molecule approved 63527-52-6 455.465 C16H17N5O7S2 Q4U2R8#Solute carrier family 22 member 6@Q8TCC7#Solute carrier family 22 member 8@Q9NSA0#Solute carrier family 22 member 11@Q9Y694#Solute carrier family 22 member 7@P46059#Solute carrier family 15 member 1@P02768#Serum albumin@Q93LQ9#Beta-lactamase@Q16348#Solute carrier family 15 member 2 Cefotaxime is a third generation intravenous cephalosporin antibiotic. It has broad spectrum activity against Gram positive and Gram negative bacteria. It does not have activity against Pseudomonas aeruginosa. Cefotaxime works by inhibiting bacterial cell wall biosynthesis. A positive feature of cefotaxime is that it display a resistance to penicillinases and is useful to treat infections that are resistant to penicillin derivatives. D0D1HA DB00494 Entacapone small molecule approved 130929-57-6 305.286 C14H15N3O5 P21964#Catechol O-methyltransferase Entacapone is structurally and pharmacologically related to tolcapone, but unlike tolcapone, is not associated with hepatotoxicity. Entacapone is used in the treatment of Parkinson’s disease as an adjunct to levodopa/carbidopa therapy. Entacapone selectively and reversiblly inhibits catechol-O-methyltransferase (COMT). In mammals, COMT is distributed throughout various organs with the highest activities in the liver and kidney. COMT also occurs in the heart, lung, smooth and skeletal muscles, intestinal tract, reproductive organs, various glands, adipose tissue, skin, blood cells and neuronal tissues, especially in glial cells. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. COMT is responsible for the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa, catalyzing the it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery. D0J1VY DB00495 Zidovudine small molecule approved 30516-87-1 267.2413 C10H13N5O4 Q72547#Reverse transcriptase/RNaseH@O14746#Telomerase reverse transcriptase Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Zidovudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. D01XYJ DB00496 Darifenacin small molecule approved 133099-04-4 426.55 C28H30N2O2 P20309#Muscarinic acetylcholine receptor M3@P08172#Muscarinic acetylcholine receptor M2 D0Y5AM DB00497 Oxycodone small molecule approved 76-42-6 315.3636 C18H21NO4 P35372#Mu-type opioid receptor@P41145#Kappa-type opioid receptor@P41143#Delta-type opioid receptor Oxycodone acts directly on a number of tissues not related to its analgesic effect. These tissues include the respiratory centre in the brain stem, the cough centre in the medulla, muscles of the pupils, gastrointestinal tract, cardiovascular system, endocrine system, and immune system.Label Oxycodone's effect on the respiratory centre is dose dependant respiratory depression.Label The action on the cough centre is suppression of the cough reflex.Label Pupils become miopic or decrease in size, peristalsis of the gastrointestinal tract slows, and muscle tone in the colon may increase causing constipation.Label In the cardiovascular system histamine may be released leading to pruritis, red eyes, flushing, sweating, and decreased blood pressure.Label Endocrine effects may include increased prolactin, decreased cortisol, and decreased testosterone.Label It is not yet known if the effects of opioids on the immune system are clinically significant.Label D03SKD DB00498 Phenindione small molecule approved 83-12-5 222.2387 C15H10O2 Q9BQB6#Vitamin K epoxide reductase complex subunit 1 Phenindione thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as Phenindione have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body). However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higer incidence of severe adverse effects. D08FTG DB00499 Flutamide small molecule approved 13311-84-7 276.2118 C11H11F3N2O3 P10275#Androgen receptor@P35869#Aryl hydrocarbon receptor@O75469#Nuclear receptor subfamily 1 group I member 2 Flutamide is a nonsteroidal antiandrogen. In animal studies, flutamide demonstrates potent antiandrogenic effects. It exerts its antiandrogenic action by inhibiting androgen uptake and/or by inhibiting nuclear binding of androgen in target tissues or both. Prostatic carcinoma is known to be androgen-sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen, e.g. castration. Elevations of plasma testosterone and estradiol levels have been noted following flutamide administration. D0Y0SW DB00500 Tolmetin small molecule approved 26171-23-3 257.2845 C15H15NO3 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Tolmetin is a nonsteroidal anti-inflammatory agent. Studies in animals have shown tolmetin to possess anti-inflammatory, analgesic and antipyretic activity. In the rat, tolmetin prevents the development of experimentally induced polyarthritis and also decreases established inflammation. In patients with either rheumatoid arthritis or osteaoarthritis, tolmetin is as effective as aspirin and indomethacin in controlling disease activity, but the frequency of the milder gastrointestinal adverse effects and tinnitus was less than in aspirin-treated patients, and the incidence of central nervous system adverse effects was less than in indomethacin-treated patients. In patients with juvenile rheumatoid arthritis, tolmetin is as effective as aspirin in controlling disease activity, with a similar incidence of adverse reactions. tolmetin has produced additional therapeutic benefit when added to a regimen of gold salts and, to a lesser extent, with corticosteroids. Tolmetin should not be used in conjunction with salicylates since greater benefit from the combination is not likely, but the potential for adverse reactions is increased. D09BHB DB00501 Cimetidine small molecule approved 51481-61-9 252.339 C10H16N6S P25021#Histamine H2 receptor Cimetidine is a histamine H2-receptor antagonist. It reduces basal and nocturnal gastric acid secretion and a reduction in gastric volume, acidity, and amount of gastric acid released in response to stimuli including food, caffeine, insulin, betazole, or pentagastrin. It is used to treat gastrointestinal disorders such as gastric or duodenal ulcer, gastroesophageal reflux disease, and pathological hypersecretory conditions. Cimetidine inhibits many of the isoenzymes of the hepatic CYP450 enzyme system. Other actions of Cimetidine include an increase in gastric bacterial flora such as nitrate-reducing organisms. D02DPA DB00502 Haloperidol small molecule approved 52-86-8 375.864 C21H23ClFNO2 P21728#D(1A) dopamine receptor@P20309#Muscarinic acetylcholine receptor M3@P08913#Alpha-2A adrenergic receptor@Q13224#Glutamate receptor ionotropic, NMDA 2B@P35367#Histamine H1 receptor@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor Use of the first-generation antipsychotics (including haloperidol) is considered highly effective for the management of the "positive" symptoms of schizophrenia including hallucinations, hearing voices, aggression/hostility, disorganized speech, and psychomotor agitation. However, this class is limited by the development of movement disorders such as drug-induced parkinsonism, akathisia, dystonia, and tardive dyskinesia, and other side effects including sedation, weight gain, and prolactin changes. Compared to the lower-potency first-generation antipsychotics such as Chlorpromazine, Zuclopenthixol, Fluphenazine, and Methotrimeprazine, haloperidol typically demonstrates the least amount of side effects within class, but demonstrates a stronger disposition for causing extrapyramidal symptoms (EPS).6,7,8 Low‐potency medications have a lower affinity for dopamine receptors so that a higher dose is required to effectively treat symptoms of schizophrenia. In addition, they block many receptors other than the primary target (dopamine receptors), such as cholinergic or histaminergic receptors, resulting in a higher incidence of side effects such as sedation, weight gain, and hypotension. D0D1AL DB00503 Ritonavir small molecule approved 155213-67-5 720.944 C37H48N6O5S2 O75469#Nuclear receptor subfamily 1 group I member 2 D0ZU9R DB00504 Levallorphan small molecule approved 152-02-3 283.4079 C19H25NO P35372#Mu-type opioid receptor Levallorphan, an opioid antagonist similar to naloxone, is used to treat drug overdoses. Levallorphan differs from naloxone in that it also possesses some agonist properties. It is an analogue of levelorphanol that counteracts the actions of narcotic analgesics such as morphine. It is used especially in the treatment of respiratory depression due to narcotic overdoses. Levallorphan prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine. D04QWE DB00507 Nitazoxanide small molecule approved 55981-09-4 307.282 C12H9N3O5S P94692#Pyruvate synthase The general effect of this medication is the prevention of microbe activity through disruption of important energy pathways for survival and proliferation Label,2. Nitazoxanide exhibits antiprotozoal activity by interfering with the pyruvate ferredoxin/flavodoxin oxidoreductase dependent electron transfer reaction, an essential reaction need for anaerobic energy metabolism of various microorganisms. Sporozoites of Cryptosporidium parvum and trophozoites of Giardia lamblia are therefore inhibited, relieving symptoms of diahrrea 10. Interference with the PFOR enzyme-dependent electron transfer reaction may only be one of the many pathways by which nitazoxanide exhibits antiprotozoal activity Label,1,10. D08EBN DB00508 Triflupromazine small molecule approved 146-54-3 352.417 C18H19F3N2S P21728#D(1A) dopamine receptor@P41595#5-hydroxytryptamine receptor 2B@P08172#Muscarinic acetylcholine receptor M2@P14416#D(2) dopamine receptor Triflupromazine is a member of a class of drugs called phenthiazines, which are dopamine D1/D2 receptor antagonists. Phenothiazines are used to treat serious mental and emotional disorders, including schizophrenia and other psychotic disorders. It reduces anxiety, emotional withdrawal, hallucinations, disorganized thoughts, blunted mood, and suspiciousness. Triflupromazine is used particularly to control violent behavior during acute episodes of psychotic disorders. It can also be used to control severe nausea and vomiting, severe hiccups, and moderate to severe pain in some hospitalized patients. Triflupromazine acts on the central nervous system. D05NOS DB00509 Dextrothyroxine small molecule approved 51-49-0 776.87 C15H11I4NO4 P10827#Thyroid hormone receptor alpha@P10828#Thyroid hormone receptor beta@P07202#Thyroid peroxidase Dextrothyroxine, the dextrorotary isomer of the synthetic thyroxine, is a antihyperlipidemic. DB00511 Acetyldigitoxin small molecule approved 1111-39-3 806.9757 C43H66O14 P05023#Sodium/potassium-transporting ATPase subunit alpha-1 The main pharmacological effects of acetyldigitoxin are on the heart. Extracardiac effects are responsible for many of the adverse effects. Its main cardiac effects are 1) a decrease of conduction of electrical impulses through the AV node, making it a commonly used drug in controlling the heart rate during atrial fibrillation or atrial flutter, and 2) an increase of force of contraction via inhibition of the Na+/K+ ATPase pump. D0V3GA DB00512 Vancomycin small molecule approved 1404-90-6 1449.254 C66H75Cl2N9O24 Vancomycin is a branched tricyclic glycosylated nonribosomal peptide often reserved as the "drug of last resort", used only after treatment with other antibiotics has failed. Vancomycin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections: Listeria monocytogenes, Streptococcus pyogenes, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus agalactiae, Actinomyces species, and Lactobacillus species. The combination of vancomycin and an aminoglycoside acts synergistically in vitro against many strains of Staphylococcus aureus, Streptococcus bovis, enterococci, and the viridans group streptococci Label. D0B1IV DB00513 Aminocaproic acid small molecule approved 60-32-2 131.1729 C6H13NO2 P00747#Plasminogen@P00750#Tissue-type plasminogen activator@P08519#Apolipoprotein(a) Aminocaproic acid works as an antifibrinolytic. It is a derivative of the amino acid lysine. The fibrinolysis-inhibitory effects of aminocaproic acid appear to be exerted principally via inhibition of plasminogen activators and to a lesser degree through antiplasmin activity. Aminocaproic acid may be a possible prophylactic for vascular disease, as it may prevent formation of lipoprotein (a), a risk factor for vascular disease. DB00514 Dextromethorphan small molecule approved 125-71-3 271.404 C18H25NO Q99720#Sigma non-opioid intracellular receptor 1@Q8TCU5#Glutamate receptor ionotropic, NMDA 3A@Q15822#Neuronal acetylcholine receptor subunit alpha-2@P31645#Sodium-dependent serotonin transporter@O00264#Membrane-associated progesterone receptor component 1@P32297#Neuronal acetylcholine receptor subunit alpha-3@P43681#Neuronal acetylcholine receptor subunit alpha-4@P30926#Neuronal acetylcholine receptor subunit beta-4@P17787#Neuronal acetylcholine receptor subunit beta-2@P36544#Neuronal acetylcholine receptor subunit alpha-7 Dextromethorphan is an opioid-like molecule indicated in combination with other medication in the treatment of coughs and pseudobulbar affect.14,15,13 It has a moderate therapeutic window, as intoxication can occur at higher doses.10 Dextromethorphan has a moderate duration of action.13 Patients should be counselled regarding the risk of intoxication.10 D09OBB DB04398 Lactic acid small molecule approved 50-21-5 90.0779 C3H6O3 P09546#Bifunctional protein PutA@Q9RW27#NimA-related protein Lactic acid produces a metabolic alkalinizing effect. DB04465 Lactose small molecule approved 63-42-3 342.2965 C12H22O11 P17931#Galectin-3@P00722#Beta-galactosidase@Q9NZD2#Glycolipid transfer protein@Q02834#Sialidase@P26514#Endo-1,4-beta-xylanase A@Q7SI98#Beta-xylanase@P16278#Beta-galactosidase Not Available D0K8XC DB04540 Cholesterol small molecule approved 57-88-5 386.6535 C27H46O Q14994#Nuclear receptor subfamily 1 group I member 3@P11473#Vitamin D3 receptor@Q9ULY5#C-type lectin domain family 4 member E@P35398#Nuclear receptor ROR-alpha Not Available D02DLW DB04564 Gluconolactone small molecule approved 90-80-2 178.14 C6H10O6 P09848#Lactase-phlorizin hydrolase Not Available D04QWD DB04570 Latamoxef small molecule approved 64952-97-2 520.473 C20H20N6O9S P02919#Penicillin-binding protein 1B@P24228#D-alanyl-D-alanine carboxypeptidase DacB Latamoxef works by inhibiting bacterial cell wall biosynthesis. D0O5LU DB04571 Trioxsalen small molecule approved 3902-71-4 228.2433 C14H12O3 Trioxsalen ispharmacologically inactive but when exposed to ultraviolet radiation or sunlight it is converted to its active metabolite to produce a beneficial reaction affecting the diseased tissue. D0FA2O DB04572 Thiotepa small molecule approved 52-24-4 189.218 C6H12N3PS The unstable nitrogen-carbon groups alkylate with DNA causing irrepairable DNA damage. They stop tumor growth by crosslinking guanine nucleobases in DNA double-helix strands, directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. These drugs act nonspecifically. D00YZA DB04573 Estriol small molecule approved 50-27-1 288.3814 C18H24O3 P03372#Estrogen receptor@P04278#Sex hormone-binding globulin@Q92731#Estrogen receptor beta Estriol (also oestriol) is one of the three main estrogens produced by the human body. It is only produced in significant amounts during pregnancy as it is made by the placenta. In pregnant women with multiple sclerosis (MS), estriol reduces the disease's symptoms noticeably, according to researchers at UCLA's Geffen Medical School. D0Z1FX DB04574 Estrone sulfate small molecule approved 481-97-0 350.429 C18H22O5S P03372#Estrogen receptor@Q92731#Estrogen receptor beta Estropipate is an estrogenic substance. It acts as naturally produced estrogen does. Estrogens act through binding to nuclear receptors in estrogen-responsive tissues. Circulating estrogens modulate the pituitary secretion of the gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), through a negative feedback mechanism. Estrogens act to reduce the elevated levels of these hormones seen in postmenopausal women. DB04575 Quinestrol small molecule approved 152-43-2 364.5204 C25H32O2 P03372#Estrogen receptor Quinestrol is the 3-cyclopentyl ether of ethinyl estradiol (the active metabolite). After gastrointestinal absorption, it is stored in adipose tissue where it is slowly released and metabolized principally to the parent compound, ethinyl estradiol. Ethinyl estradiol is a synthetic derivative of the natural estrogen estradiol. D04UZT DB04657 Carboxin small molecule approved 5234-68-4 235.302 C12H13NO2S P31040#Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial Not Available DB04703 Hesperidin small molecule approved 520-26-3 610.5606 C28H34O15 Q96GD4#Aurora kinase B Not Available D0I9HF DB04711 Iodipamide small molecule approved 606-17-7 1139.7618 C20H14I6N2O6 Following intravenous administration of Cholografin Meglumine, iodipamide is carried to the liver where it is rapidly secreted. The contrast medium appears in the bile within 10 to 15 minutes after injection, thus permitting visualization of the hepatic and common bile ducts, even in cholecystectomized patients. The biliary ducts are readily visualized within about 25 minutes after administration, except in patients with impaired liver function. The gallbladder begins to fill within an hour after injection; maximum filling is reached after two to two and one-half hours. The contrast medium is finally eliminated in the feces without passing through the enterohepatic circulation, except for approximately 10 percent of the intravenously administered dose which is excreted through the kidneys. D07OIX DB04743 Nimesulide small molecule approved 51803-78-2 308.31 C13H12N2O5S P35354#Prostaglandin G/H synthase 2@Q9NZK7#Group IIE secretory phospholipase A2@P02788#Lactotransferrin Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics. D0C0JT DB04794 Bifonazole small molecule approved 60628-96-8 310.3917 C22H18N2 P20813#Cytochrome P450 2B6 Bifonazole is a type of antifungal medicine known as an imidazole. It kills fungi and yeasts by interfering with their cell membranes. D0AA2D DB04812 Benoxaprofen small molecule approved 51234-28-7 301.724 C16H12ClNO3 Not Available D00CCI DB04813 Bithionol small molecule approved 97-18-7 356.052 C12H6Cl4O2S Not Available DB04815 Clioquinol small molecule approved 130-26-7 305.5 C9H5ClINO Clioquinol is a broad-spectrum antibacterial with antifungal properties. Application of clioquinol to extensive or eroded areas of the skin may lead to increased protein-bound iodine (PBI) levels within 1 week. In addition, elevated PBI levels may occur when relatively small areas of the skin are treated with clioquinol for more than 1 week. DB04816 Dantron small molecule approved 117-10-2 240.2109 C14H8O4 Not Available DB04817 Metamizole small molecule approved 50567-35-6 311.36 C13H17N3O4S P23219#Prostaglandin G/H synthase 1 Dipyrone is a non-steroidal anti-inflammatory drug (NSAID), commonly used in the past as a powerful painkiller and fever reducer. D06JRD DB04820 Nialamide small molecule approved 51-12-7 298.3397 C16H18N4O2 P27338#Amine oxidase [flavin-containing] B@P21397#Amine oxidase [flavin-containing] A@P21964#Catechol O-methyltransferase Not Available DB04821 Nomifensine small molecule approved 24526-64-5 238.3275 C16H18N2 P23975#Sodium-dependent noradrenaline transporter@Q01959#Sodium-dependent dopamine transporter@P27338#Amine oxidase [flavin-containing] B@P21397#Amine oxidase [flavin-containing] A@P05164#Myeloperoxidase@P31645#Sodium-dependent serotonin transporter@Q05940#Synaptic vesicular amine transporter Nomifensine is a dopamine reuptake inhibitor test-marketed in the United States by Hoechst AG (now Novartis) that increases the amount of synaptic dopamine available to receptors by blocking dopamine's re-uptake transporter. Nomifensine is now mainly used in scientific research, particularly in studies involving dopamine release in response to addiction. D06BPG DB04822 Oxeladin small molecule approved 468-61-1 335.4809 C20H33NO3 Not Available DB04824 Phenolphthalein small molecule approved 77-09-8 318.3228 C20H14O4 O60656#UDP-glucuronosyltransferase 1-9@O75469#Nuclear receptor subfamily 1 group I member 2@Q14994#Nuclear receptor subfamily 1 group I member 3@P04278#Sex hormone-binding globulin Not Available D03FDT DB04825 Prenylamine small molecule approved 390-64-7 329.4779 C24H27N P0DP23#Calmodulin@Q9H1R3#Myosin light chain kinase 2, skeletal/cardiac muscle Not Available DB04826 Thenalidine small molecule approved 86-12-4 286.435 C17H22N2S Not Available DB04827 Urethane small molecule approved 51-79-6 89.0932 C3H7NO2 Not Available DB04832 Zimelidine small molecule approved 56775-88-3 317.23 C16H17BrN2 P27338#Amine oxidase [flavin-containing] B@P21397#Amine oxidase [flavin-containing] A@P31645#Sodium-dependent serotonin transporter Zimelidine was the first marketed selective serotonin reuptake inhibitor (SSRI) antidepressant. It is a pyridylallylamine, structurally different from other antidepressants. DB04834 Rapacuronium small molecule approved 465499-11-0 597.904 C37H61N2O4 P08172#Muscarinic acetylcholine receptor M2 Rapacuronium is a rapidly acting, non-depolarizing neuromuscular blocker. DB04835 Maraviroc small molecule approved 376348-65-1 513.6655 C29H41F2N5O P51681#C-C chemokine receptor type 5 Maraviroc is a chemokine receptor antagonist drug developed by the drug company Pfizer that is designed to act against HIV by interfering with the interaction between HIV and CCR5. D0NR6S DB04837 Clofedanol small molecule approved 791-35-5 289.8 C17H20ClNO P70174#Histamine H1 receptor Chlophedianol (or Clofedanol) is a centrally-acting cough suppressant. It has local anesthetic and antihistamine properties, and may have anticholinergic effects at high doses. DB04838 Cyclandelate small molecule approved 456-59-7 276.3707 C17H24O3 P54289#Voltage-dependent calcium channel subunit alpha-2/delta-1@P23141#Liver carboxylesterase 1 Cyclandelate is in a class of drugs called vasodilators. Cyclandelate relaxes veins and arteries, which makes them wider and allows blood to pass through them more easily. D05VQI DB04839 Cyproterone acetate small molecule approved 427-51-0 416.938 C24H29ClO4 P10275#Androgen receptor@P07288#Prostate-specific antigen Cyproterone is an antiandrogen. It suppresses the actions of testosterone (and its metabolite dihydrotestosterone) on tissues. It acts by blocking androgen receptors which prevents androgens from binding to them and suppresses luteinizing hormone (which in turn reduces testosterone levels). DB04840 Debrisoquine small molecule approved 1131-64-2 175.2303 C10H13N3 P23975#Sodium-dependent noradrenaline transporter Debrisoquin is an adrenergic neuron-blocking drug similar in effects to guanethidine. It is a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism. DB04841 Flunarizine small molecule approved 52468-60-7 404.4948 C26H26F2N2 O43497#Voltage-dependent T-type calcium channel subunit alpha-1G@O95180#Voltage-dependent T-type calcium channel subunit alpha-1H@Q9P0X4#Voltage-dependent T-type calcium channel subunit alpha-1I@P0DP23#Calmodulin@P70174#Histamine H1 receptor Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 blocking activity. D05CEU DB04842 Fluspirilene small molecule approved 1841-19-6 475.5727 C29H31F2N3O P28223#5-hydroxytryptamine receptor 2A@Q06432#Voltage-dependent calcium channel gamma-1 subunit Fluspirilene is a relatively long-acting injectable depot antipsychotic drug used for schizophrenia. Fluspirilene does not differ greatly from other depot antipsychotics (fluphenazine decanoate, fluphenazine enathate, perphenazine onanthat, pipotiazine undecylenate) with respect to treatment efficacy, response or tolerability. Outcomes suggest that fluspirilene does not differ significantly from oral antipsychotics or in different weekly regimens, although much cannot be inferred because of the shortage of trials. D0U5FS DB04843 Mepenzolate small molecule approved 25990-43-6 340.436 C21H26NO3 P11229#Muscarinic acetylcholine receptor M1@P20309#Muscarinic acetylcholine receptor M3 Mepenzolate diminishes gastric acid and pepsin secretion. Mepenzolate also suppresses spontaneous contractions of the colon. Pharmacologically, it is a post-ganglionic parasympathetic inhibitor. D0FV3V DB04844 Tetrabenazine small molecule approved 58-46-8 317.4226 C19H27NO3 Q05940#Synaptic vesicular amine transporter Prolongation of the QTc interval has been observed at doses of 50 mg. In rats, it has been observed that tetrabenazine or its metabolites bind to melanin-containing tissues such as the eyes and skin. After a single oral dose of radiolabeled tetrabenazine, radioactivity was still detected in eye and fur at 21 days post dosing. D09PJX DB04845 Ixabepilone small molecule approved 219989-84-1 506.7 C27H42N2O5S Q13509#Tubulin beta-3 chain Not Available D0W2EK DB04846 Celiprolol small molecule approved 56980-93-9 379.501 C20H33N3O4 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P18825#Alpha-2C adrenergic receptor Not Available DB04854 Febuxostat small molecule approved 144060-53-7 316.375 C16H16N2O3S P47989#Xanthine dehydrogenase/oxidase Febuxostat is a novel, selective xanthine oxidase/dehydrogenase inhibitor that works by decreasing serum uric acid in a dose-dependent manner. In healthy subjects, febuxostat decreased the mean serum uric acid and serum xanthine concentrations, as well as the total urinary uric acid excretion. Febuxostat at daily doses of 40-80 mg reduced the 24-hour mean serum uric acid concentrations by 40 to 55%.10 Closely related to the drug-induced reduction of serum uric acid levels and mobilization of urate crystals in tissue deposits, febuxostat is associated with gout flares.7 D0A5SE DB04855 Dronedarone small molecule approved 141626-36-0 556.756 C31H44N2O5S Q12809#Potassium voltage-gated channel subfamily H member 2@Q14524#Sodium channel protein type 5 subunit alpha@O95069#Potassium channel subfamily K member 2@P08913#Alpha-2A adrenergic receptor@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@P18089#Alpha-2B adrenergic receptor@P51787#Potassium voltage-gated channel subfamily KQT member 1@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q9UK17#Potassium voltage-gated channel subfamily D member 3@P48050#Inward rectifier potassium channel 4 D05CPV DB04861 Nebivolol small molecule approved 118457-14-0 405.435 C22H25F2NO4 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor Nebivolol is a selective beta-1 adrenergic receptor antagonist that decreases vascular resistance, increases stroke volume and cardiac output, and does not negatively affect left ventricular function.2,3 It has a long duration of action as effects can be seen 48 hours after stopping the medication and a wide therapeutic window as patients generally take 5-40mg daily.2,9 Patients should not abruptly stop taking this medication as this may lead to exacerbation of coronary artery disease.9 Diabetic patients should monitor their blood glucose levels as beta blockers may mask signs of hypoglycemia.9 D0Z1UA DB04864 Huperzine A small molecule approved 102518-79-6 242.3162 C15H18N2O P22303#Acetylcholinesterase Huperzine A is an alkaloid derived from Huperzia serrata (which is available as an herbal product in the US). It is under investigation as an acetylcholinesterase inhibitor. Clinical trials in China have shown that huperzine A is comparably effective to the drugs currently on the market, and may even be somewhat safer in terms of side effects. D06XWB DB04865 Omacetaxine mepesuccinate small molecule approved 26833-87-4 545.6213 C29H39NO9 P39023#60S ribosomal protein L3@P20276#50S ribosomal protein L2 The pharmacodynamics of homoharringtonine is not fully understood. It is known that homoharringtonine is involved D0M4XY DB04868 Nilotinib small molecule approved 641571-10-0 529.5158 C28H22F3N7O P00519#Tyrosine-protein kinase ABL1@P10721#Mast/stem cell growth factor receptor Kit Nilotinib is a transduction inhibitor that targets BCR-ABL, c-kit and PDGF, for the potential treatment of various leukemias, including chronic myeloid leukemia (CML). D00STL DB04871 Lorcaserin small molecule approved 616202-92-7 195.69 C11H14ClN D01JMC DB04876 Vildagliptin small molecule approved 274901-16-5 303.3993 C17H25N3O2 P27487#Dipeptidyl peptidase 4 Vildagliptin works to improve glycemic control in type II diabetes mellitus by enhancing the glucose sensitivity of beta-cells (β-cells) in pancreatic islets and promoting glucose-dependent insulin secretion. Increased GLP-1 levels leads to enhanced sensitivity of alpha cells to glucose, promoting glucagon secretion. Vildagliptin causes an increase in the insulin to glucagon ratio by increasing incretin hormone levels: this results in a decrease in fasting and postprandial hepatic glucose production. Vildagliptin does not affect gastric emptying. It also has no effects on insulin secretion or blood glucose levels in individuals with normal glycemic control.6 D0L3DK DB04880 Enoximone small molecule approved 77671-31-9 248.301 C12H12N2O2S Q14432#cGMP-inhibited 3',5'-cyclic phosphodiesterase A Enoximone is a phosphodiesterase inhibitor (type III) that increases the force of contraction of the heart and dilates blood vessels. In June 2005, Myogen announced that they were discontinuing development of enoximone due to negative results. The drug is approved for use in the UK. D0E0SW DB04890 Bepotastine small molecule approved 125602-71-3 388.888 C21H25ClN2O3 P70174#Histamine H1 receptor Bepotastine is a non-sedating, selective antagonist of the histamine 1 (H1) receptor. It belongs to the second-generation piperidine chemical class. It is a mast cell stabilizer and suppresses the migration of eosinophils into inflamed tissues. Furthermore, bepotastine does not interact with serotonin, muscarinic, benzodiazepine, and beta-adrenergic receptor that would otherwise result in adverse reactions such as dry mouth or sonmolence. D0U5VZ DB04896 Milnacipran small molecule approved 92623-85-3 246.354 C15H22N2O Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B When utilized to treat fibromyalgia, the effect of milnacipran on the QTcF interval in patients was measured in a double-blind placebo-and positive-controlled parallel study in 88 healthy subjects using three to six times the recommended therapeutic dose for fibromyalgia at 600 mg/day 26. After baseline and placebo adjustment, the maximum mean QTcF change was 8 ms - an increase that is generally not considered to be clinically significant 26. D09VGC DB04898 Ximelagatran small molecule approved 192939-46-1 473.5652 C24H35N5O5 P00734#Prothrombin Not Available D0JQ7Y DB04908 Flibanserin small molecule approved 167933-07-5 390.4021 C20H21F3N4O P08908#5-hydroxytryptamine receptor 1A@P28223#5-hydroxytryptamine receptor 2A Not Available D0S9CB DB04911 Oritavancin small molecule approved 171099-57-3 1793.101 C86H97Cl3N10O26 Oritavancin interferes with bacterial cell wall synthesis and integrity, treating susceptible skin and subcutaneous tissue infections with gram-positive bacteria.3,10 This drug is known to artifically increase INR and aPTT, interfering with coagulation testing. Cases of infusion reactions have also been reported.10 D02IBU DB04918 Ceftobiprole small molecule approved 209467-52-7 534.57 C20H22N8O6S2 Q7DHH4#MecA Ceftobiprole, a cephalosporin antibiotic, is active against methicillin-resistant Staphylococcus aureus. D0CI9T DB04920 Clevidipine small molecule approved 167221-71-8 456.316 C21H23Cl2NO6 O60840#Voltage-dependent L-type calcium channel subunit alpha-1F@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C Clevidipine belongs to a well-known class of drugs called dihydropyridine calcium channel antagonists. Clevidpine is the first third generation intravenous dihydropyridine calcium channel blocker. In vitro studies demonstrated that clevidipine acts by selectively relaxing the smooth muscle cells that line small arteries, resulting in arterial dilation, widening of the artery opening, and without reducing central venous pressure or reducing cardiac output. DB04930 Permethrin small molecule approved 52645-53-1 391.288 C21H20Cl2O3 P35498#Sodium channel protein type 1 subunit alpha@O75469#Nuclear receptor subfamily 1 group I member 2 Permethrin, a pyrethroid, is active against a broad range of pests including lice, ticks, fleas, mites, and other arthropods. D0K8MP DB04931 Afamelanotide small molecule approved 75921-69-6 1646.8452 C78H111N21O19 Q01726#Melanocyte-stimulating hormone receptor Afamelanotide increases the production of eumelanin, an endogenous photoprotective agent, to attenuate UV-induced skin damage in patients with a condition that predisposes them to phototoxicity.4 It has a relatively long duration of therapeutic effect despite its short half-life due to its ability to increase melanosome density and therefore skin pigmentation.2 As afamelanotide may darken pre-existing skin pigmentary lesions, patients receiving afamelanotide should undergo a full body skin examination every 6 months to monitor for progression or worsening of any skin abnormalities.4 Standard sun safety measures should continue to be employed during afamelanotide therapy.4 D0V2OX DB04938 Ospemifene small molecule approved 128607-22-7 378.891 C24H23ClO2 P03372#Estrogen receptor The half maximal inhibitory concentration (IC50) for estrogen receptor (ER) alpha and beta are 0.8 μM and 1.7 μM, respectively. Ospemifene has potential uses in the management of osteoporosis in postmenopausal women. It interacts with osteoblasts and osteoclasts in such a way that it reduces bone turnover. It also has potential uses in the prevention of breast cancer. Studies suggest that ospemifene, in a dose-dependent manner, reduces the incidence of tumours. D02CTS DB04946 Iloperidone small molecule approved 133454-47-4 426.4806 C24H27FN2O4 P28223#5-hydroxytryptamine receptor 2A@P08908#5-hydroxytryptamine receptor 1A@P50406#5-hydroxytryptamine receptor 6@P34969#5-hydroxytryptamine receptor 7@P35348#Alpha-1A adrenergic receptor@P70174#Histamine H1 receptor@P18825#Alpha-2C adrenergic receptor Iloperidone shows high affinity and maximal receptor occupancy for dopamine D2 receptors in the caudate nucleus and putamen of the brains of schizophrenic patients. The improvement in cognition is attributed to iloperidone's high affinity for α adrenergic receptors. Iloperidone also binds with high affinity to serotonin 5-HT2a and dopamine 3 receptors. Iloperidone binds with moderate affinity to dopamine D4, serotonin 5-HT6 and 5-HT7, and norepinephrine NEα1 receptors. Furthermore, iloperidone binds with weak affinity to serotonin 5-HT1A, dopamine D1, and histamine H1 receptors. D0M8VE DB04948 Lofexidine small molecule approved 31036-80-3 259.132 C11H12Cl2N2O P08913#Alpha-2A adrenergic receptor@P35348#Alpha-1A adrenergic receptor@P08908#5-hydroxytryptamine receptor 1A@P34969#5-hydroxytryptamine receptor 7@P28335#5-hydroxytryptamine receptor 2C@P28221#5-hydroxytryptamine receptor 1D In clinical trials, lofexidine presented more severe opioid withdrawal effects than observed with methadone. On the other hand, in clinical trials of methadone withdrawal, lofexidine effectively reduced withdrawal symptoms, especially hypotension.5 The clinical reports have also indicated that lofexidine presents a better outcome when used briefly.6 In phase 3 clinical trials, lofexidine was shown to generate a significantly higher completion rate of opioid discontinuation. Some pharmacological studies were performed and there were no off-target effects reported.9 D0K0MW DB04951 Pirfenidone small molecule approved 53179-13-8 185.2218 C12H11NO Pirfenidone is a novel agent with anti-inflammatory, antioxidant, and antifibrotic properties. It may improve lung function and reduce the number of acute exacerbations in patients with idiopathic pulmonary fibrosis (IPF). D02WCI DB04953 Ezogabine small molecule approved 150812-12-7 303.3314 C16H18FN3O2 O43526#Potassium voltage-gated channel subfamily KQT member 2@O43525#Potassium voltage-gated channel subfamily KQT member 3@P56696#Potassium voltage-gated channel subfamily KQT member 4@Q9NR82#Potassium voltage-gated channel subfamily KQT member 5 As compared to other antiepileptic agents, ezogabine is unique in that it selectively activates potassium ion channels Kv 7.2-Kv7.5 and not cardiac Kv 7.1, thereby avoiding cardiac side effects. The antiepileptics, as a drug class, are routinely used in the treatment of a number of disease states in addition to epilepsy. Ezogabine is highly efficacious in a broad-spectrum of in vivo epilepsy and seizure models. A comparison of antiepileptic form activity of ezogabine with that of conventional anticonvulsants in in vitro models suggests that retigabine is especially likely to be useful in the treatment of pharmacoresistant epilepsy. Retigabine clearly attenuates pain-like behaviors in various animal models of neuropathic pain; it may also prove to be useful in treatment of clinical anxiety disorders. Clinical data obtained thus far indicate that retigabine is well tolerated in humans when titrated up to its therapeutic dose range. No tolerance, drug dependence, or withdrawal liability has been reported. Thus, retigabine may prove to be useful in the treatment of a diverse range of disease states in which neuronal hyperexcitability is a common underlying factor. DB05013 Ingenol mebutate small molecule approved 75567-37-2 430.541 C25H34O6 P17252#Protein kinase C alpha type@Q05655#Protein kinase C delta type D0E9KA DB05015 Belinostat small molecule approved 866323-14-0 318.35 C15H14N2O4S Q13547#Histone deacetylase 1@Q92769#Histone deacetylase 2@O15379#Histone deacetylase 3@P56524#Histone deacetylase 4@Q9UQL6#Histone deacetylase 5@Q9UBN7#Histone deacetylase 6@Q8WUI4#Histone deacetylase 7@Q9BY41#Histone deacetylase 8 Beleodaq is a histone deacetylase (HDAC) inhibitor that exhibits pan-HDAC inhibition and potent growth inhibitory and pro-apoptotic activities in a variety of tumor cells, including PTCL cells, at nanomolar concentrations 2. None of the trials show any clinically relevant changes caused by Beleodaq on heart rate, PR duration or QRS duration as measures of autonomic state, atrio-ventricular conduction or depolarization; there were no cases of Torsades de Pointes. DB05016 Ataluren small molecule approved 775304-57-9 284.242 C15H9FN2O3 Not Available D09IRQ DB05018 Migalastat small molecule approved 108147-54-2 163.1717 C6H13NO4 P06280#Alpha-galactosidase A In general, treatment in patients with migalastat in Phase 2 pharmacodynamic trials resulted in increases in endogenous alpha-galactosidase (alpha-Gal A) activity in white blood cells, as well as in skin and kidney for the majority of patients Label,6. In patients with amenable galactosidase alpha gene (GLA) mutations, globotriaosylceramide (GL-3) levels tended to decrease in the urine and in the kidney interstitial capillaries Label,6. D0MU9L DB05039 Indacaterol small molecule approved 312753-06-3 392.4907 C24H28N2O3 P07550#Beta-2 adrenergic receptor Bronchodilator drugs are the foundation for the treatment of chronic obstructive pulmonary disease. The principal inhaled bronchodilator treatments used are β(2) -agonists and anticholinergics, either alone or in combination. Currently available β(2) -agonists are of either short duration and used multiple times/day, or of long duration, which requires twice-daily administration. Indacaterol is considered an ultra-long-acting β(2) -agonist and was recently approved for use in the United States. Its duration of action is approximately 24 hours, allowing for once-daily administration. Furthermore, this chiral compound it is given as the R-enantiomer and acts as a full agonist. Cough was the most commonly reported adverse effect with use of indacaterol. Compared to salmeterol, it has 35% more agonist activity. Cough usually occurred within 15 seconds of inhalation of the drug, lasted around 6 seconds, was not associated with bronchospasm, and did not cause discontinuation of the drug. Otherwise, the drug's safety profile was similar to that of other bronchodilators. [PMID: 22499359] D03DJL DB05057 Erdosteine small molecule approved 84611-23-4 249.307 C8H11NO4S2 Not Available D0K3VA DB05109 Trabectedin small molecule approved 114899-77-3 761.837 C39H43N3O11S Two of the rings in the drug's structure allows it to covalently bind to the minor groove of DNA. The third ring protrudes from the DNA which lets it interact with nearby nuclear proteins. This has the additive effect of blocking cell division at the G2 phase. D03RTK DB05154 Pretomanid small molecule approved 187235-37-6 359.2574 C14H12F3N3O5 P9WGR1#Enoyl-[acyl-carrier-protein] reductase [NADH]@P9WIP7#Nucleoid-associated protein Lsr2 Pretomanid kills the actively replicating bacteria causing tuberculosis, known as Mycobacterium tuberculosis, and shortens the duration of treatment in patients who suffer from resistant forms of pulmonary TB by killing dormant bacteria.4,5,7,10 D02AYL DB05219 Crisaborole small molecule approved 906673-24-3 251.05 C14H10BNO3 P27815#cAMP-specific 3',5'-cyclic phosphodiesterase 4A@Q07343#cAMP-specific 3',5'-cyclic phosphodiesterase 4B@Q08493#cAMP-specific 3',5'-cyclic phosphodiesterase 4C@Q08499#cAMP-specific 3',5'-cyclic phosphodiesterase 4D Crisaborole has broad-spectrum anti-inflammatory activity by mainly targeting phosphodiesterase 4 (PDE4) enzyme that is a key regulator of inflammatory cytokine production. As this enzyme is expressed in keratinocytes and immune cells, crisaborole mediates an anti-inflammatory effect on almost all inflammatory cells. Topical application of this drug is useful as it potentiates the localization of this drug in the skin and this anti-inflammatory activity is in the low micromolar range. DB05239 Cobimetinib small molecule approved 934660-93-2 531.318 C21H21F3IN3O2 Q02750#Dual specificity mitogen-activated protein kinase kinase 1 Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase 1 (MAPK)/extracellular signal regulated kinase 1 (MEK1) and MEK2. Preclinical studies have demonstrated that this agent is effective in inhibiting the growth of tumor cells bearing a BRAF mutation, which has been found to be associated with many tumor types. A threonine-tyrosine kinase and a key component of the RAS/RAF/MEK/ERK signalling pathway that is frequently activated in human tumors, MEK1 is required for the transmission of growth-promoting signals from numerous receptor tyrosine kinases. Cobimetinib is used in combination with vemurafenib because the clinical benefit of a BRAF inhibitor is limited by intrinsic and acquired resistance. Reactivation of the MAPK pathway is a major contributor to treatment failure in BRAF-mutant melanomas, approximately ~80% of melanoma tumors becomes BRAF-inhibitor resistant due to reactivation of MAPK signalling. BRAF-inhibitor resistant tumor cells are sensitive to MEK inhibition, therefore cobimetinib and vemurafenib will result in dual inhibition of BRAF and its downstream target, MEK. DB05245 Silver sulfadiazine small molecule approved 22199-08-2 357.137 C10H9AgN4O2S Silver sulfadiazine has broad antimicrobial activity. It is bactericidal for many gram- negative and gram-positive bacteria as well as being effective against yeast. Silver sulfadiazine is not a carbonic anhydrase inhibitor and may be useful in situations where such agents are contraindicated. D08JCA DB05246 Methsuximide small molecule approved 77-41-8 203.2371 C12H13NO2 O43497#Voltage-dependent T-type calcium channel subunit alpha-1G Used in the treatment of epilepsy. Methsuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli. D08EOD DB05260 Gallium nitrate small molecule approved 13494-90-1 255.738 GaN3O9 P31350#Ribonucleoside-diphosphate reductase subunit M2@P21281#V-type proton ATPase subunit B, brain isoform@P02818#Osteocalcin@P01584#Interleukin-1 beta@Q9S427#Protein-tyrosine-phosphatase Gallium nitrate exerts hypocalcemic effect by inhibiting calcium resorption from bone, possibly by stabilizing bone matrix, thereby reducing increased bone turnover. Gallium nitrate inhibits the growth of various lymphoma cell lines in vitro and exhibits antitumor activity in patients with lymphoma. The mechanism(s) of cytotoxicity is (are) only partly understood but appears to involve a two-step process: (1) targeting of gallium to cells, and (2) acting on multiple, specific intracellular processes. Gallium shares certain chemical properties with iron; therefore, it binds avidly to the iron transport protein transferrin. Transferrin-gallium complexes preferentially target cells that express transferrin receptors on their surface. Expression of transferrin receptors is particularly high on lymphoma cells. Cellular uptake of the gallium-transferrin complex leads to inhibition of cellular proliferation primarily via disruption of iron transport and homeostasis and blockade of ribonucleotide reductase. Recent studies have shown that cellular uptake of gallium leads to activation of caspases and induction of apoptosis. In phase II trials in patients with relapsed or refractory lymphoma, the antitumor activity of gallium nitrate is similar to, or better than, that of other commonly used chemotherapeutic agents. D0R4ZT DB05271 Rotigotine small molecule approved 99755-59-6 315.48 C19H25NOS P21728#D(1A) dopamine receptor@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor Rotigotine is an agonist at all 5 dopamine receptor subtypes (D1-D5) but binds to the D3 receptor with the highest affinity. It is also an antagonist at α-2-adrenergic receptors and an agonist at the 5HT1A receptors. Rotigotine also inhibits dopamine uptake and prolactin secretion. There is no indication of a QT/QTc prolonging effect of Neupro in doses up to 24 mg/24 hours. The effects of Neupro at doses up to 24 mg/24 hours (supratherapeutic doses) on the QT/QTc interval was evaluated in a double-blind, randomized, placebo- and positive-controlled (moxifloxacin 400 mg IV, single dose) parallel-group trial with an overall treatment period of 52 days in male and female patients with advanced-stage Parkinson's disease. Assay sensitivity was confirmed by significant QTc prolongation by moxifloxacin. DB05273 Samarium (153Sm) lexidronam small molecule approved 122575-21-7 586.021 C6H17N2O12P4Sm Not Available DB05294 Vandetanib small molecule approved 443913-73-3 475.354 C22H24BrFN4O2 P15692#Vascular endothelial growth factor A@P00533#Epidermal growth factor receptor@Q13882#Protein-tyrosine kinase 6@Q02763#Angiopoietin-1 receptor@P07949#Proto-oncogene tyrosine-protein kinase receptor Ret Mean IC50 of approximately 2.1 μg/mL. D0G6QF DB05316 Pimavanserin small molecule approved 706779-91-1 427.564 C25H34FN3O2 P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@Q99720#Sigma non-opioid intracellular receptor 1 Pimavanserin's unique actions on serotonin receptors improve symptoms of hallucinations and delusions associated with Parkinson's disease.2 In clinical studies, 80.5% of individuals treated with pimavanserin reported improvement in symptoms. Pimavanserin does not worsen motor functioning in patients with Parkinson's disease psychosis.9 D0J8JP DB05351 Dexlansoprazole small molecule approved 138530-94-6 369.36 C16H14F3N3O2S P51164#Potassium-transporting ATPase subunit beta@P20648#Potassium-transporting ATPase alpha chain 1 Dexlansoprazole is a proton pump inhibitor (PPI) and is included in the drug class of antisecretory compounds. It blocks the final step of gastric acid secretion by specific inhibition of the (H+, K+)-ATPase at the secretory surface of the parietal cells on gastric mucosa. D06YYD DB05381 Histamine small molecule approved 51-45-6 111.1451 C5H9N3 P70174#Histamine H1 receptor@P25021#Histamine H2 receptor@Q9Y5N1#Histamine H3 receptor@Q9H3N8#Histamine H4 receptor@Q05940#Synaptic vesicular amine transporter Histamine stimulates gastric gland secretion, causing an increased secretion of gastric juice of high acidity. This action is probably due mainly to a direct action on parietal and chief gland cells. DB05382 Iodine small molecule approved 7553-56-2 253.8089 I2 Q92911#Sodium/iodide cotransporter Not Available DB05389 Tetrachlorodecaoxide small molecule approved 92047-76-2 319.821 Cl4H2O11 Q7L5Y9#Macrophage erythroblast attacher@Q86VB7#Scavenger receptor cysteine-rich type 1 protein M130 Not Available DB00515 Cisplatin small molecule approved 15663-27-1 300.05 Cl2H6N2Pt P29372#DNA-3-methyladenine glycosylase@P01023#Alpha-2-macroglobulin@P02787#Serotransferrin@O00244#Copper transport protein ATOX1 Cisplatin is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. D0U5HU DB00517 Anisotropine methylbromide small molecule approved 80-50-2 362.345 C17H32BrNO2 P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3 Anisotropine methylbromide is a quaternary ammonium compound. Its use as treatment adjunct in peptic ulcer has been replaced by the use of more effective agents. Depending on the dose, anisotropine methylbromide may reduce the motility and secretory activity of the gastrointestinal system, and the tone of the ureter and urinary bladder and may have a slight relaxant action on the bile ducts and gallbladder. In general, smaller doses of anisotropine methylbromide inhibit salivary and bronchial secretions, sweating, and accommodation; cause dilatation of the pupil; and increase the heart rate. Larger doses are required to decrease motility of the gastrointestinal and urinary tracts and to inhibit gastric acid secretion. DB00518 Albendazole small molecule approved 54965-21-8 265.331 C12H15N3O2S F1L7U3#Tubulin beta-2 chain@Q71U36#Tubulin alpha-1A chain@P68371#Tubulin beta-4B chain Albendazole is a broad-spectrum anthelmintic. The principal mode of action for albendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules. D00KVO DB00519 Trandolapril small molecule approved 87679-37-6 430.5372 C24H34N2O5 P12821#Angiotensin-converting enzyme Trandolapril is the ethyl ester prodrug of a nonsulfhydryl ACE inhibitor, trandolaprilat. Trandolapril is deesterified in the liver to the diacid metabolite, trandolaprilat, which is approximately eight times more active as an inhibitor of ACE than its parent compound. ACE is a peptidyl dipeptidase that is part of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure via a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may further sustain the effects of trandolaprilat by causing increased vasodilation and decreased blood pressure. The blood pressure lowering effect of trandolaprilat is due to a decrease in peripheral vascular resistance, which is not accompanied by significant changes in urinary excretion of chloride or potassium or water or sodium retention. D0M5OC DB00520 Caspofungin small molecule approved 162808-62-0 1093.3131 C52H88N10O15 Caspofungin is an antifungal drug, and belongs to a new class termed the echinocandins. It is used to treat Aspergillus and Candida infection, and works by inhibiting cell wall synthesis. Antifungals in the echinocandin class inhibit the synthesis of glucan in the cell wall, probably via the enzyme 1,3-beta glucan synthase. There is a potential for resistance development to occur, however in vitro resistance development to Caspofungin by Aspergillus species has not been studied. D00ZCN DB00521 Carteolol small molecule approved 51781-06-7 292.3734 C16H24N2O3 P07550#Beta-2 adrenergic receptor@P08588#Beta-1 adrenergic receptor Carteolol is a beta1 and beta2 (non-selective) adrenergic receptor-blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity. Carteolol, when applied topically to the eye, has the action of reducing elevated, as well as normal, intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss and optic nerve damage. Carteolol reduces intraocular pressure with little or no effect on pupil size or accommodation in contrast to the miosis which cholinergic agents are known to produce. D03GCJ DB00523 Alitretinoin small molecule approved 5300-03-8 300.4351 C20H28O2 P10276#Retinoic acid receptor alpha@P19793#Retinoic acid receptor RXR-alpha@P10826#Retinoic acid receptor beta@P28702#Retinoic acid receptor RXR-beta@P13631#Retinoic acid receptor gamma@P48443#Retinoic acid receptor RXR-gamma@P17936#Insulin-like growth factor-binding protein 3@Q15238#Pregnancy-specific beta-1-glycoprotein 5@Q6V0L0#Cytochrome P450 26C1 Alitretinoin (9-cis-retinoic acid) is a naturally-occurring endogenous retinoid indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Alitretinoin inhibits the growth of Kaposi's sarcoma (KS) cells in vitro. D0G3PI DB00524 Metolazone small molecule approved 17560-51-9 365.835 C16H16ClN3O3S P55017#Solute carrier family 12 member 3 Metolazone is a quinazoline diuretic, with properties generally similar to the thiazide diuretics. A proximal action of metolazone has been shown in humans by increased excretion of phosphate and magnesium ions and by a markedly increased fractional excretion of sodium in patients with severely compromised glomerular filtration. This action has been demonstrated in animals by micropuncture studies. D01WLC DB00525 Tolnaftate small molecule approved 2398-96-1 307.409 C19H17NOS Q92206#Squalene monooxygenase Tolnaftate is a synthetic over-the-counter anti-fungal agent. D02NTO DB00526 Oxaliplatin small molecule approved 61825-94-3 397.294 C8H14N2O4Pt D0Y3ME DB00527 Cinchocaine small molecule approved 85-79-0 343.4632 C20H29N3O2 Q14524#Sodium channel protein type 5 subunit alpha@Q9Y5Y9#Sodium channel protein type 10 subunit alpha@P0DP23#Calmodulin Dibucaine is an amide-type local anesthetic, similar to lidocaine. DB00528 Lercanidipine small molecule approved 100427-26-7 611.7272 C36H41N3O6 Q06432#Voltage-dependent calcium channel gamma-1 subunit Lercanidipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Lercanidipine is similar to other peripheral vasodilators. Lercanidipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. D0P6ZH DB00529 Foscarnet small molecule approved 4428-95-9 126.0053 CH3O5P P09252#DNA polymerase catalytic subunit@P09252#DNA polymerase catalytic subunit Foscarnet is an organic analogue of inorganic pyrophosphate that inhibits replication of herpes viruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Foscarnet does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Thus, HSV strains resistant to acyclovir or CMV strains resistant to ganciclovir may be sensitive to foscarnet. However, acyclovir or ganciclovir resistant mutants with alterations in the viral DNA polymerase may be resistant to foscarnet and may not respond to therapy with foscarnet. The combination of foscarnet and ganciclovir has been shown to have enhanced activity in vitro. DB00530 Erlotinib small molecule approved 183321-74-6 393.4357 C22H23N3O4 O75469#Nuclear receptor subfamily 1 group I member 2@P00533#Epidermal growth factor receptor Not Available D07POC DB00531 Cyclophosphamide small molecule approved 50-18-0 261.086 C7H15Cl2N2O2P O75469#Nuclear receptor subfamily 1 group I member 2 Cyclophosphamide is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. D0CT9C DB00532 Mephenytoin small molecule approved 50-12-4 218.2518 C12H14N2O2 Q14524#Sodium channel protein type 5 subunit alpha@O75469#Nuclear receptor subfamily 1 group I member 2 Mephenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, mephenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of posttetanic potentiation at synapses. Loss of posttetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. Mephenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures. D07RGW DB00533 Rofecoxib small molecule approved 162011-90-7 314.356 C17H14O4S P35354#Prostaglandin G/H synthase 2@P15502#Elastin Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Unlike celecoxib, rofecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Like other NSAIDs, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activity. NSAIDs appear to inhibit prostaglandin synthesis via the inhibition of cyclooxygenase (COX), which are responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathyway. There are at least two isoenzymes, COX-1 and COX-2, that have been identified. Although the exact mechanisms have not been clearly established, NSAIDs exert their anti-inflammatory, analgesic, and antipyretic primarily through the inhibition of COX-2. The inhibition of COX-1 is principally responsible for the negative effects on the GI mucosa. As rofecoxib is selective for COX-2, it may be potentially associated with a decreased risk of certain adverse events, but more data is needed to fully evaulate the drug. D05VLS DB00534 Chlormerodrin small molecule approved 62-37-3 367.2 C5H11ClHgN2O2 Q13621#Solute carrier family 12 member 1@P51649#Succinate-semialdehyde dehydrogenase, mitochondrial Chlormerodrin is a mercurial compound with toxic side effects. It is no longer used and has been replaced with new classes of diuretic drugs. D06EMT DB00535 Cefdinir small molecule approved 91832-40-5 395.414 C14H13N5O5S2 D6R448#Penicillin-binding protein 2@Q60FT7#PBP3@P05164#Myeloperoxidase Cefdinir is a bactericidal agent that treats bacterial infections by interfering with cell wall synthesis.14 D0WS1X DB00536 Guanidine small molecule approved 113-00-8 59.0705 CH5N3 P05091#Aldehyde dehydrogenase, mitochondrial@P07998#Ribonuclease pancreatic@P78352#Disks large homolog 4@Q37875#Lysozyme@Q14353#Guanidinoacetate N-methyltransferase@P53608#Arginase Guanidine apparently acts by enhancing the release of acetylcholine following a nerve impulse. It also appears to slow the rates of depolarization and repolarization of muscle cell membranes. DB00537 Ciprofloxacin small molecule approved 85721-33-1 331.3415 C17H18FN3O3 P11388#DNA topoisomerase 2-alpha@Q12809#Potassium voltage-gated channel subfamily H member 2@P0C1U9#DNA topoisomerase 4 subunit A@C3T8E2#Multidrug resistance protein MdtK@B4YQT9#Gyrase A@P05653#DNA gyrase subunit A Ciprofloxacin is a second generation fluoroquinolone that is active against many Gram negative and Gram positive bacteria.9,18,19,20,21,22,23,24,25,26 It produces its action through inhibition of bacterial DNA gyrase and topoisomerase IV.12 Ciprofloxacin binds to bacterial DNA gyrase with 100 times the affinity of mammalian DNA gyrase.13 There is no cross resistance between fluoroquinolones and other classes of antibiotics, so it may be of clinical value when other antibiotics are no longer effective.13 Ciprofloxain and its derivatives are also being investigated for its action against malaria, cancers, and AIDS.12 DB00538 Gadoversetamide small molecule approved 131069-91-5 661.76 C20H34GdN5O10 Not Available D0X0GI DB00539 Toremifene small molecule approved 89778-26-7 405.96 C26H28ClNO P03372#Estrogen receptor@P04278#Sex hormone-binding globulin Toremifene is an antineoplastic hormonal agent primarily used in the treatment of advanced breast cancer. Toremifene is a nonsteroidal agent that has demonstrated potent antiestrogenic properties in animal test systems. The antiestrogenic effects may be related to its ability to compete with estrogen for binding sites in target tissues such as breast. Toremifene inhibits the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes the regression of already established DMBA-induced tumors. In this rat model, Toremifene appears to exert its antitumor effects by binding the estrogen receptors. In cytosols derived from human breast adenocarcinomas, Toremifene competes with estradiol for estrogen receptor protein. D04VFJ DB00540 Nortriptyline small molecule approved 72-69-5 263.3767 C19H21N P35367#Histamine H1 receptor@P14416#D(2) dopamine receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P08909#5-hydroxytryptamine receptor 2C@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3 Nortriptyline exerts antidepressant effects likely by inhibiting the reuptake of serotonin and norepinephrine at neuronal cell membranes. It also exerts antimuscarinic effects through its actions on the acetylcholine receptor.18,19 D04WFD DB00541 Vincristine small molecule approved 57-22-7 824.972 C46H56N4O10 Q7KQL5#Tubulin beta chain@P68366#Tubulin alpha-4A chain Vincristine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific. D09QVV DB00542 Benazepril small molecule approved 86541-75-5 424.4895 C24H28N2O5 P12821#Angiotensin-converting enzyme Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which, when hydrolyzed by esterases to its active Benazeprilat1, is used to treat hypertension and heart failure, to reduce proteinuria and renal disease in patients with nephropathies, and to prevent stroke, myocardial infarction, and cardiac death in high-risk patients5,3,2. Benazepril and Benazeprilat inhibit angiotensin-converting enzyme (ACE) in human subjects and animals5,1. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin IILabel. Angiotensin II also stimulates aldosterone secretion by the adrenal cortexLabel. D0U3EC DB00543 Amoxapine small molecule approved 14028-44-5 313.781 C17H16ClN3O P31645#Sodium-dependent serotonin transporter@P23975#Sodium-dependent noradrenaline transporter@P08913#Alpha-2A adrenergic receptor@P35348#Alpha-1A adrenergic receptor@P11229#Muscarinic acetylcholine receptor M1@P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P50406#5-hydroxytryptamine receptor 6@P34969#5-hydroxytryptamine receptor 7 Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class, chemically distinct from the dibenzodiazepines, dibenzocycloheptenes, and dibenzoxepines. It has a mild sedative component to its action. The mechanism of its clinical action in man is not well understood. In animals, amoxapine reduced the uptake of nor-epinephirine and serotonin and blocked the response of dopamine receptors to dopamine. Amoxapine is not a monoamine oxidase inhibitor. Clinical studies have demonstrated that amoxapine has a more rapid onset of action than either amitriptyline or imipramine D09IOI DB00544 Fluorouracil small molecule approved 51-21-8 130.0772 C4H3FN2O2 P04818#Thymidylate synthase Fluorouracil is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances from becoming incorporated into DNA during the "S" phase (of the cell cycle), stopping normal development and division. Fluorouracil blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Fluorouracil blocks the incorporation of the thymidine nucleotide into the DNA strand. D05LEO DB00545 Pyridostigmine small molecule approved 155-97-5 181.2117 C9H13N2O2 P06276#Cholinesterase@P22303#Acetylcholinesterase Pyridostigmine bromide, designated as 3-hydroxy-1-methyl-pyridinium bromide dimethyl-carbamate, is an orally active reversible cholinesterase inhibitor similar to neostigmine but with a milder adverse effect profile and a longer duration of action. Pyridostigmine may, specifically in the case of excessive administration, result in a cholinergic crisis, with symptoms mimicking a myasthenic crisis. Administration of atropine is recommended in the case of a true cholinergic crisis or to counteract muscarinic/nicotinic effects such as bradycardia and excessive bronchial secretions.10,11 D0O2WB DB00547 Desoximetasone small molecule approved 382-67-2 376.4617 C22H29FO4 P04150#Glucocorticoid receptor Like other topical corticosteroids, desoximetasone has anti-inflammatory, antipruritic, and vasoconstrictive properties. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Desoximetasone is a potent topical corticosteroid that should not be used with occlusive dressings. It is recommended that treatment should be limited to 2 consecutive weeks and therapy should be discontinued when adequate results have been achieved. D0CZ1Q DB00548 Azelaic acid small molecule approved 123-99-9 188.2209 C9H16O4 P51857#3-oxo-5-beta-steroid 4-dehydrogenase@P31213#3-oxo-5-alpha-steroid 4-dehydrogenase 2@P14679#Tyrosinase Azelaic acid is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. It is a natural substance that is produced by Malassezia furfur (also known as Pityrosporum ovale), a yeast that lives on normal skin. It is effective against a number of skin conditions, such as mild to moderate acne, when applied topically in a cream formulation of 20%. It works in part by stopping the growth of skin bacteria that cause acne, and by keeping skin pores clear. Azelaic acid's antimicrobial action may be attributable to inhibition of microbial cellular protein synthesis. DB00549 Zafirlukast small molecule approved 107753-78-6 575.675 C31H33N3O6S Q9Y271#Cysteinyl leukotriene receptor 1 Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA) indicated for the prophylaxis and chronic treatment of asthma. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD4 than nonasthmatic subjects. In vitro studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC4, LTD4 and LTE4) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD4-induced increases in cutaneous vascular permeability and inhibited inhaled LTD4-induced influx of eosinophils into animal lungs. D05DVP DB00550 Propylthiouracil small molecule approved 51-52-5 170.232 C7H10N2OS P07202#Thyroid peroxidase Propylthiouracil is a thiourea antithyroid agent. Grave's disease is the most common cause of hyperthyroidism. It is an autoimmune disease where an individual's own antibodies attach to thyroid stimulating hormone receptors within cells of the thyroid gland and then trigger overproduction of thyroid hormone. The two thyroid hormones manufactured by the thyroid gland, thyroxine (T4) and triiodothyronine (T3), are formed by combining iodine and a protein called thyroglobulin with the assistance of an enzyme called peroxidase. PTU inhibits iodine and peroxidase from their normal interactions with thyroglobulin to form T4 and T3. This action decreases thyroid hormone production. PTU also interferes with the conversion of T4 to T3, and, since T3 is more potent than T4, this also reduces the activity of thyroid hormones. The actions and use of propylthiouracil are similar to those of methimazole. D00MIN DB00551 Acetohydroxamic acid small molecule approved 546-88-3 75.0666 C2H5NO2 P18314#Urease subunit alpha@P39900#Macrophage metalloelastase Acetohydroxamic Acid, a synthetic drug derived from hydroxylamine and ethyl acetate, is similar in structure to urea. In the urine, it acts as an antagonist of the bacterial enzyme urease. Acetohydroxamic Acid has no direct antimicrobial action and does not acidify urine directly. DB00552 Pentostatin small molecule approved 53910-25-1 268.2691 C11H16N4O4 Q8IJA9#Adenosine deaminase Pentostatin is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia and hairy cell leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Cytotoxicity is cell cycle phase-specific (S-phase). D0T3AD DB00553 Methoxsalen small molecule approved 298-81-7 216.192 C12H8O4 Methoxsalen selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of Methoxsalen-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. D08SKH DB00554 Piroxicam small molecule approved 36322-90-4 331.346 C15H13N3O4S P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Piroxicam is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Piroxicam works by reducing hormones that cause inflammation and pain in the body. Piroxicam is used to reduce the pain, inflammation, and stiffness caused by rheumatoid arthritis and osteoarthritis. D00IBN DB00555 Lamotrigine small molecule approved 84057-84-1 256.091 C9H7Cl2N5 Q15878#Voltage-dependent R-type calcium channel subunit alpha-1E@Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha Lamotrigine likely prevents seizures and prevents mood symptoms via stabilizing presynaptic neuronal membranes and preventing the release of excitatory neurotransmitters such as glutamate, which contribute to seizure activity.10,14 D03FLC DB00556 Perflutren small molecule approved 76-19-7 188.0193 C3F8 Perflutren, a diagnostic drug that is intended to be used for contrast enhancement during the indicated echocardiographic procedures, comprised of lipid-coated microspheres filled with octafluoropropane(OFP) gas. It provide contrast enhancement of the endocardial borders during echocardiography. The perflutren lipid microspheres exhibit lower acoustic impedance than blood and enhance the intrinsic backscatter of blood. DB00557 Hydroxyzine small molecule approved 68-88-2 374.904 C21H27ClN2O2 P70174#Histamine H1 receptor@Q12809#Potassium voltage-gated channel subfamily H member 2 Hydroxyzine blocks the activity of histamine to relieve allergic symptoms such as pruritus.18 Activity at off-targets also allows for its use as a sedative anxiolytic and an antiemetic in certain disease states.15 D0O6SX DB00558 Zanamivir small molecule approved 139110-80-8 332.3098 C12H20N4O7 Q9Y3R4#Sialidase-2@P27907#Neuraminidase Zanamivir, an antiviral agent, is a neuraminidase inhibitor indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years and older who have been symptomatic for no more than 2 days. Zanamivir has also been shown to significantly inhibit the human sialidases NEU3 and NEU2 in the micromolar range (Ki 3.7 +/-0.48 and 12.9+/-0.07 microM, respectively), which could account for some of the rare side effects of zanamivir. D00NPP DB00559 Bosentan small molecule approved 147536-97-8 551.614 C27H29N5O6S P24530#Endothelin B receptor@P25101#Endothelin-1 receptor Bosentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Bosentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects. D0U4CE DB00560 Tigecycline small molecule approved 220620-09-7 585.6487 C29H39N5O8 P0A7X3#30S ribosomal protein S9@P0A7S3#30S ribosomal protein S12@P0AG59#30S ribosomal protein S14@P0A7S9#30S ribosomal protein S13@P0A7U3#30S ribosomal protein S19 Tigecycline is the first clinically-available drug in a new class of antibiotics called the glycylcyclines. Glycylcyclines are a new class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection. Glycylcycline antibiotics have a similar mechanism of action as tetracycline antibiotics. Both classes of antibiotics bind to the 30S ribosomal subunit to prevent the amino-acyl tRNA from binding to the A site of the ribosome. However, the glycylcyclines appear to bind more effectively than the tetracyclines. D0G4OD DB00561 Doxapram small molecule approved 309-29-5 378.5072 C24H30N2O2 O14649#Potassium channel subfamily K member 3@Q9NPC2#Potassium channel subfamily K member 9 Doxapram is an analeptic agent (a stimulant of the central nervous system). The respiratory stimulant action is manifested by an increase in tidal volume associated with a slight increase in respiratory rate. A pressor response may result following doxapram administration. Provided there is no impairment of cardiac function, the pressor effect is more marked in hypovolemic than in normovolemic states. The pressor response is due to the improved cardiac output rather than peripheral vasoconstriction. Following doxapram administration, an increased release of catecholamines has been noted. D0M7BT DB00562 Benzthiazide small molecule approved 91-33-8 431.937 C15H14ClN3O4S3 P00915#Carbonic anhydrase 1@Q8N1Q1#Carbonic anhydrase 13@Q9ULX7#Carbonic anhydrase 14@P00918#Carbonic anhydrase 2@P07451#Carbonic anhydrase 3@P22748#Carbonic anhydrase 4@P23280#Carbonic anhydrase 6@P43166#Carbonic anhydrase 7@Q16790#Carbonic anhydrase 9 Benzthiazide is used to treat hypertension and edema. Like other thiazides, benzthiazide promotes water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. D0L2MX DB00563 Methotrexate small molecule approved 59-05-2 454.4393 C20H22N8O5 P04818#Thymidylate synthase@P31939#Bifunctional purine biosynthesis protein PURH@P00378#Dihydrofolate reductase Methotrexate inhibits enzymes responsible for nucleotide synthesis which prevents cell division and leads to anti-inflammatory actions.1 It has a long duration of action and is generally given to patients once weekly.1,4,5,6 Methotrexate has a narrow therapeutic index.2 D0SV8E DB00564 Carbamazepine small molecule approved 298-46-4 236.2686 C15H12N2O P43681#Neuronal acetylcholine receptor subunit alpha-4@O75469#Nuclear receptor subfamily 1 group I member 2@Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha General effects D04MSM DB00565 Cisatracurium small molecule approved 96946-41-7 929.16 C53H72N2O12 Q15822#Neuronal acetylcholine receptor subunit alpha-2 Cisatracurium Besylate is a nondepolarizing skeletal muscle relaxant for intravenous administration. Cisatracurium Besylate acts on cholinergic receptors, blocking neuromuscular transmission. This action is antagonized by acetylcholinesterase inhibitors such as neostigmine. The neuromuscular block produced by cisatracurium besylate is readily antagonized by anticholinesterase agents once recovery has started. As with other nondepolarizing neuromuscular blocking agents, the more profound the neuromuscular block at the time of reversal, the longer the time required for recovery of neuromuscular function. Compared to other neuromuscular blocking agents, it is intermediate in its onset and duration of action. D08ALK DB00566 Succimer small molecule approved 304-55-2 182.21 C4H6O4S2 Succimer is an orally active, heavy metal chelating agent. It forms water soluble chelates and, consequently, increases the urinary excretion of lead. Succimer is not to be used for prophylaxis of lead poisoning in a lead-containing environment. In addition, the use of succimer should always be accompanied by identification and removal of the source of the lead exposure. D01GYK DB00567 Cephalexin small molecule approved 15686-71-2 347.389 C16H17N3O4S P0A3M6#Penicillin-binding protein 2B@Q8DR59#Penicillin-binding protein 1A@Q7CRA4#Penicillin-binding protein 1b Cephalexin (also called Cefalexin) is a first generation cephalosporin antibiotic.7,8 It is one of the most widely prescribed antibiotics, often used for the treatment of superficial infections that result as complications of minor wounds or lacerations.Label It is effective against most gram-positive bacteria through its inihibition of the cross linking reaction between N-acetyl muramicacid and N-acetylglucosamine in the cell wall, leading to cell lysis.9 D0Z5EM DB00568 Cinnarizine small molecule approved 298-57-7 368.5139 C26H28N2 P70174#Histamine H1 receptor@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@O60840#Voltage-dependent L-type calcium channel subunit alpha-1F@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O43497#Voltage-dependent T-type calcium channel subunit alpha-1G@O95180#Voltage-dependent T-type calcium channel subunit alpha-1H@Q9P0X4#Voltage-dependent T-type calcium channel subunit alpha-1I Cinnarizine is an antihistamine and a calcium channel blocker. Histamines mediate a number of activities such as contraction of smooth muscle of the airways and gastrointestinal tract, vasodilatation, cardiac stimulation, secretion of gastric acid, promotion of interleukin release and chemotaxis of eosinophils and mast cells. Competitive antagonists at histamine H1 receptors may be divided into first (sedating) and second (non-sedating) generation agents. Some, such as Cinnarizine also block muscarinic acetylcholine receptors and are used as anti-emetic agents. Cinnarizine through its calcium channel blocking ability also inhibits stimulation of the vestibular system. D0Q3YO DB00569 Fondaparinux small molecule approved 104993-28-4 1508.263 C31H53N3O49S8 P00742#Coagulation factor X@P01008#Antithrombin-III Fondaparinux binds specifically to the natural anticoagulant factor, ATIII. Binding to ATIII potentiates the neutralizing action of ATIII on Factor Xa 300-times. Neutralization of Factor Xa decreases the conversion of prothrombin to thrombin, which subsequently decreases the conversion of fibrinogen to fibrin (loose meshwork). The decrease in thrombin also decreases the activation of Factor XIII, which decreases the conversion of fibrin in its loose meshwork form to its stabilized meshwork form. Disruption of the coagulation cascade effectively decreases the formation of blood clots. Fondaparinux does not inactivate thrombin (activated Factor II). According to the manufacturer, fondaparinux has no known effect on platelet function. In studies comparing fondaparinux to enoxaparin, decreases in platelet levels were observed in similar numbers of patients from both groups (2-5%) 1,2. At the recommended dose, Fondaparinux does not affect fibrinolytic activity or bleeding time. There is no antidote for fondaparinux. Monitoring of the anticoagulant activity of fondaparinux is not generally required. The anti-factor Xa assay may be used to monitor therapy in special populations such as those with renal impairment or who are pregnant. Complete blood count (CBC) and kidney function should be monitored during treatment. DB00570 Vinblastine small molecule approved 865-21-4 810.9741 C46H58N4O9 Q71U36#Tubulin alpha-1A chain@Q7KQL5#Tubulin beta chain@Q9UJT1#Tubulin delta chain@P23258#Tubulin gamma-1 chain@Q9UJT0#Tubulin epsilon chain@P05412#Transcription factor AP-1 Vinblastine is a vinca alkaloid antineoplastic agent. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units: vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vinblastine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific. D0W9MM DB00571 Propranolol small molecule approved 525-66-6 259.3434 C16H21NO2 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P08908#5-hydroxytryptamine receptor 1A@P28222#5-hydroxytryptamine receptor 1B Propranolol is a beta-adrenergic receptor antagonist used to treat hypertension9,10. Propranolol has a long duration of action as it is given once or twice daily depending on the indication.8,9,10 When patients abruptly stop taking propranolol, they may experience exacerbations of angina and myocardial infarctions.10 D04JEE DB00572 Atropine small molecule approved 51-55-8 289.3694 C17H23NO3 P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5@P23415#Glycine receptor subunit alpha-1@P43681#Neuronal acetylcholine receptor subunit alpha-4@P17787#Neuronal acetylcholine receptor subunit beta-2 Atropine, a naturally occurring belladonna alkaloid, is a racemic mixture of equal parts of d- and l-hyoscyamine, whose activity is due almost entirely to the levo isomer of the drug. Atropine is commonly classified as an anticholinergic or antiparasympathetic (parasympatholytic) drug. More precisely, however, it is termed an antimuscarinic agent since it antagonizes the muscarine-like actions of acetylcholine and other choline esters. Adequate doses of atropine abolish various types of reflex vagal cardiac slowing or asystole. The drug also prevents or abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus. Atropine may also lessen the degree of partial heart block when vagal activity is an etiologic factor. Atropine in clinical doses counteracts the peripheral dilatation and abrupt decrease in blood pressure produced by choline esters. However, when given by itself, atropine does not exert a striking or uniform effect on blood vessels or blood pressure. D0RG3O DB00573 Fenoprofen small molecule approved 29679-58-1 242.2699 C15H14O3 P35354#Prostaglandin G/H synthase 2@Q07869#Peroxisome proliferator-activated receptor alpha@P37231#Peroxisome proliferator-activated receptor gamma@P23219#Prostaglandin G/H synthase 1 Fenoprofen is a propionic acid derivative with analgesic, antiinflammatory and antipyretic properties. Fenoprofen inhibits prostaglandin synthesis by decreasing the enzyme needed for biosynthesis. In patients with rheumatoid arthritis, the anti-inflammatory action of fenoprofen has been evidenced by relief of pain, increase in grip strength, and reductions in joint swelling, duration of morning stiffness, and disease activity (as assessed by both the investigator and the patient). In patients with osteoarthritis, the anti-inflammatory and analgesic effects of fenoprofen have been demonstrated by reduction in tenderness as a response to pressure and reductions in night pain, stiffness, swelling, and overall disease activity (as assessed by both the patient and the investigator). These effects have also been demonstrated by relief of pain with motion and at rest and increased range of motion in involved joints. In patients with rheumatoid arthritis and osteoarthritis, clinical studies have shown fenoprofen to be comparable to aspirin in controlling the aforementioned measures of disease activity, but mild gastrointestinal reactions (nausea, dyspepsia) and tinnitus occurred less frequently in patients treated with fenoprofen than in aspirin-treated patients. It is not known whether fenoprofen causes less peptic ulceration than does aspirin. In patients with pain, the analgesic action of fenoprofen has produced a reduction in pain intensity, an increase in pain relief, improvement in total analgesia scores, and a sustained analgesic effect. D03XYW DB00574 Fenfluramine small molecule approved 458-24-2 231.2573 C12H16F3N P41595#5-hydroxytryptamine receptor 2B D09WNK DB00575 Clonidine small molecule approved 4205-90-7 230.094 C9H9Cl2N3 P18089#Alpha-2B adrenergic receptor@P18825#Alpha-2C adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor Clonidine functions through agonism of alpha-2 adrenoceptors which have effects such as lowering blood pressure, sedation, and hyperpolarization of nerves.2 It has a long duration of action as it is given twice daily and the therapeutic window is between 0.1mg and 2.4mg daily.8,9,10,11 D03SKR DB00576 Sulfamethizole small molecule approved 144-82-1 270.331 C9H10N4O2S2 P0AC13#Dihydropteroate synthase Sulfamethizole is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus. D07JJS DB00577 Valaciclovir small molecule approved 124832-26-4 324.3357 C13H20N6O4 P13159#Thymidine kinase@P09252#DNA polymerase catalytic subunit Antiviral effects D04QJD DB00578 Carbenicillin small molecule approved 4697-36-3 378.4 C17H18N2O6S P0AEB2#D-alanyl-D-alanine carboxypeptidase DacA@P24228#D-alanyl-D-alanine carboxypeptidase DacB@P08506#D-alanyl-D-alanine carboxypeptidase DacC@P02919#Penicillin-binding protein 1B Carbenicillin is a semisynthetic penicillin. Though carbenicillin provides substantial in vitro activity against a variety of both gram-positive and gram-negative microorganisms, the most important aspect of its profile is in its antipseudomonal and antiproteal activity. Because of the high urine levels obtained following administration, carbenicillin has demonstrated clinical efficacy in urinary infections due to susceptible strains of: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Pseudomonas species, Providencia rettgeri, Enterobacter species, and Enterococci (S. faecalis). D02TBI DB00579 Mazindol small molecule approved 22232-71-9 284.74 C16H13ClN2O P23975#Sodium-dependent noradrenaline transporter@Q01959#Sodium-dependent dopamine transporter@P31645#Sodium-dependent serotonin transporter@Q05940#Synaptic vesicular amine transporter Mazindol is a sympathomimetic amine that stimulates the central nervous system (nerves and brain), leading to increased your heart rate and blood pressure, and decreased appetite. Since the appetite-suppressing effect of the drug tends to decrease after few weeks of treatment, sympathomimetic appetite suppressants are typically used short-term weight-loss program. D0H8QL DB00580 Valdecoxib small molecule approved 181695-72-7 314.359 C16H14N2O3S P35354#Prostaglandin G/H synthase 2@P00918#Carbonic anhydrase 2@P07451#Carbonic anhydrase 3 Valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Valdecoxib is used for its anti-inflammatory, analgesic, and antipyretic activities in the management of osteoarthritis (OA) and for the treatment of dysmenorrhea or acute pain. Unlike celecoxib, valdecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. D0L6DA DB00581 Lactulose small molecule approved 4618-18-2 342.2965 C12H22O11 Lactulose formulations are most commonly administered via the oral route or the rectal route.4 Consequently, because the substance experiences minimal absorption by the gut it typically remains localized in the gastrointestinal tract environment and ultimately demonstrates almost all of its pharmacologic effects within the gut.Label,3,4 In particular, as lactulose elicits its laxative effects in enhancing stool amounts and softening stool, such biochemical and physiologic activities can cause increased bowel sounds (borborygmi), a feeling of bloatedness, belching, frequent flatus, and diarrhea.Label,3,4 D0T5BC DB00582 Voriconazole small molecule approved 137234-62-9 349.3105 C16H14F3N5O Voriconazole is a fungistatic triazole antifungal used to treat infections by inhibiting fungal growth.13 It is known to cause hepatotoxic and photosensitivity reactions in some patients. D0N3VR DB00583 Levocarnitine small molecule approved 541-15-1 161.1989 C7H15NO3 P50416#Carnitine O-palmitoyltransferase 1, liver isoform@P43155#Carnitine O-acetyltransferase@P05164#Myeloperoxidase@P47989#Xanthine dehydrogenase/oxidase@P23141#Liver carboxylesterase 1 DB00584 Enalapril small molecule approved 75847-73-3 376.4467 C20H28N2O5 P12821#Angiotensin-converting enzyme Enalapril is an antihypertensive agent that exhibits natriuretic and uricosuric properties. Enalapril lowers blood pressure in all grades of essential and renovascular hypertension, and peripheral vascular resistance without causing an increase in heart rate.6 Individuals with low-renin hypertensive population were still responsive to enalapril.Label The duration of hypertensive effect in the systolic and diastolic blood pressure persists for at least 24 hours following initial administration of a single oral dose, and repeated daily administration of enalapril confers an additional reduction in blood pressure and a steady-state antihypertensive response may take several weeks.7 In patients with severe congestive heart failure and inadequate clinical response to conventional antihypertensive therapies, treatment with enalapril resulted in improvements in cardiac performance as observed by a reduction in both preload and afterload, and improved clinical status long-term.6 Furthermore, enalapril was shown to increase cardiac output and stroke volume while decreasing pulmonary capillary wedge pressure in patients with congestive heart failure refractory to conventional treatment with digitalis and diuretics. In clinical studies, enalapril reduced left ventricular mass, and did not affect cardiac function or myocardial perfusion during exercise.5 Enalapril is not highly associated with the risk of bradycardia unlike most diuretics and beta-blockers 6 and it does not produce rebound hypertension upon discontinuation of therapy.5 D00SEB DB00585 Nizatidine small molecule approved 76963-41-2 331.45 C12H21N5O2S2 P25021#Histamine H2 receptor Nizatidine is a competitive, reversible inhibitor of histamine at the histamine H2-receptors, particularly those in the gastric parietal cells. By inhibiting the action of histamine on stomach cells, nizatidine reduces stomach acid production. Nizatidine had no demonstrable antiandrogenic action. Full-dose therapy for the problems treated by nizatidine lasts no longer than 8 weeks. It has been demonstrated that treatment with a reduced dose of nizatidine is effective as maintenance therapy following healing of active duodenal ulcers. D0Q9DK DB00586 Diclofenac small molecule approved 15307-86-5 296.149 C14H11Cl2NO2 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Diclofenac reduces inflammation and by extension reduces nociceptive pain and combats fever.Label,17 It also increases the risk of developing a gastrointestinal ulcer by inhibiting the production of protective mucus in the stomach. D0TG1H DB00588 Fluticasone propionate small molecule approved 80474-14-2 500.571 C25H31F3O5S P04150#Glucocorticoid receptor@P06401#Progesterone receptor@P47712#Cytosolic phospholipase A2@P08235#Mineralocorticoid receptor Systemically, fluticasone propionate activates glucocorticoid receptors, and inhibits lung eosinophilia in rats10Label. Fluticasone propionate as a topical formulation is also associated with vasoconstriction in the skin9,3. DB00589 Lisuride small molecule approved 18016-80-3 338.4466 C20H26N4O P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P08908#5-hydroxytryptamine receptor 1A@P28221#5-hydroxytryptamine receptor 1D@P41595#5-hydroxytryptamine receptor 2B@P28222#5-hydroxytryptamine receptor 1B@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P18825#Alpha-2C adrenergic receptor@P34969#5-hydroxytryptamine receptor 7 There is evidence that lisuride lowers prolactin levels and, in low doses, prevents migraine attacks. D0X7KB DB00590 Doxazosin small molecule approved 74191-85-8 451.4751 C23H25N5O5 P35348#Alpha-1A adrenergic receptor@P25100#Alpha-1D adrenergic receptor@P35368#Alpha-1B adrenergic receptor Doxazosin decreases standing and supine blood pressure5 and relieves the symptoms of benign prostatic hypertrophy through the inhibition of alpha-1 receptors. D03MIR DB00591 Fluocinolone acetonide small molecule approved 67-73-2 452.4882 C24H30F2O6 P04150#Glucocorticoid receptor@P04083#Annexin A1@P07355#Annexin A2@P12429#Annexin A3@P09525#Annexin A4@P08758#Annexin A5@P04054#Phospholipase A2 Fluocinolone acetonide is a synthetic anti-inflammatory corticosteroid and thus, the effect of its interaction with the body produces vasoconstriction and suppression of membrane permeability, mitotic activity, immune response and release of inflammatory mediators.18 DB00592 Piperazine small molecule approved 110-85-0 86.1356 C4H10N2 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Piperazine is an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms, which is a condition primarily seen in children. Piperazine hydrate and piperazine citrate are the main anthelminthic piperazines. D01XLM DB00593 Ethosuximide small molecule approved 77-67-8 141.1677 C7H11NO2 O43497#Voltage-dependent T-type calcium channel subunit alpha-1G Used in the treatment of epilepsy. Ethosuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli. D0Q4XQ DB00594 Amiloride small molecule approved 2609-46-3 229.627 C6H8ClN7O P37088#Amiloride-sensitive sodium channel subunit alpha@P51168#Amiloride-sensitive sodium channel subunit beta@P51170#Amiloride-sensitive sodium channel subunit gamma@P51172#Amiloride-sensitive sodium channel subunit delta@P19801#Amiloride-sensitive amine oxidase [copper-containing]@Q16515#Acid-sensing ion channel 2@P78348#Acid-sensing ion channel 1@P19634#Sodium/hydrogen exchanger 1@P00749#Urokinase-type plasminogen activator Amiloride, an antikaliuretic-diuretic agent, is a pyrazine-carbonyl-guanidine that is unrelated chemically to other known antikaliuretic or diuretic agents. It is an antihypertensive, potassium-sparing diuretic that was first approved for use in 1967 and helps to treat hypertension and congestive heart failure. The drug is often used in conjunction with thiazide or loop diuretics. Due to its potassium-sparing capacities, hyperkalemia (high blood potassium levels) are occasionally observed in patients taking amiloride. The risk is high in concurrent use of ACE inhibitors or spironolactone. Patients are also advised not to use potassium-containing salt replacements. D0I0RJ DB00595 Oxytetracycline small molecule approved 79-57-2 460.434 C22H24N2O9 P0A7V8#30S ribosomal protein S4@P0A7X3#30S ribosomal protein S9 Oxytetracycline is known as a broad-spectrum antibiotic due to its activity against such a wide range of infections. It was the second of the tetracyclines to be discovered. Oxytetracycline, like other tetracyclines, is used to treat many infections common and rare. Its better absorption profile makes it preferable to tetracycline for moderately severe acne, but alternatives sould be sought if no improvement occurs by 3 months. D0J2NK DB00596 Ulobetasol small molecule approved 98651-66-2 428.9 C22H27ClF2O4 P04150#Glucocorticoid receptor Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.2 Ulobetasol has a moderate duration of action as it is applied once or twice daily.7,8 Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.2 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.2 DB00597 Gadoteridol small molecule approved 120066-54-8 558.68 C17H29GdN4O7 Not Available D0M1PL DB00598 Labetalol small molecule approved 36894-69-6 328.4055 C19H24N2O3 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor Labetalol antagonizes various adrenergic receptors to decrease blood pressure.5,3,4,7 The duration of action is long as it is generally given twice daily, and the therapeutic window is wide as patients usually take 200-400mg twice daily.8 Patients susceptible to bronchospasms should not use labetalol unless they are unresponsive to or intolerant of other antihypertensives.8 D0A8XN DB00599 Thiopental small molecule approved 76-75-5 242.338 C11H18N2O2S P20309#Muscarinic acetylcholine receptor M3@Q13002#Glutamate receptor ionotropic, kainate 2@P42262#Glutamate receptor 2@P43681#Neuronal acetylcholine receptor subunit alpha-4@P36544#Neuronal acetylcholine receptor subunit alpha-7 Thiopental, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Thiopental is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia D00MYT DB00600 Monobenzone small molecule approved 103-16-2 200.2332 C13H12O2 D0H6TP DB00601 Linezolid small molecule approved 165800-03-3 337.3461 C16H20FN3O4 Linezolid is an oxazolidinone antibacterial agent effective against most strains of aerobic Gram-positive bacteria and mycobacteria. It appears to be bacteriostatic against both staphylococci and enterococci and bactericidal against most isolates of streptococci.9 Linezolid has shown some in vitro activity against Gram-negative and anaerobic bacteria but is not considered efficacious against these organisms.9 D07UYO DB00602 Ivermectin small molecule approved 70288-86-7 1736.1589 C95H146O28 D09YHJ DB00603 Medroxyprogesterone acetate small molecule approved 71-58-9 386.5244 C24H34O4 P03372#Estrogen receptor@P06401#Progesterone receptor@P28472#Gamma-aminobutyric acid receptor subunit beta-3 Medroxyprogesterone acetate (MPA) inhibits gonadotropin production, reduces nuclear estrogen receptors and DNA synthesis in epithelial cells of the endometrium, and induces p53 dependant apoptosis in cancer cell lines.11,6 MPA oral tablets have a half life of 40-60 hours and other formulations can have half lives that are considerably longer, so the duration of action is long.2,3 The therapeutic window is wide as patients may take doses ranging from 5mg orally daily to 1000mg as a depo injection weekly.10,11,12,13,14 Long term use of MPA is associated with a reduction in bone density and patients who taking MPA during adolescence may have lower peak bone mass than untreated patients, which can also increase the risk of osteoporosis and fractures in the future.10,11,12,13,14 DB00604 Cisapride small molecule approved 81098-60-4 465.945 C23H29ClFN3O4 Q13639#5-hydroxytryptamine receptor 4@P46098#5-hydroxytryptamine receptor 3A@P28223#5-hydroxytryptamine receptor 2A@Q12809#Potassium voltage-gated channel subfamily H member 2 Cisapride is a parasympathomimetic which acts as a serotonin 5-HT4 agonist; upon activation of the receptor signaling pathway, cisapride promotes the release of acetylcholine neurotransmitters in the enteric nervous system. Cisapride stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. Cisapride increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder. Cisapride does not induce muscarinic or nicotinic receptor stimulation, nor does it inhibit acetylcholinesterase activity. D0BD8D DB00605 Sulindac small molecule approved 38194-50-2 356.411 C20H17FO3S P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1@P15121#Aldose reductase@P27361#Mitogen-activated protein kinase 3@Q03181#Peroxisome proliferator-activated receptor delta@Q9Y5Y4#Prostaglandin D2 receptor 2@O60218#Aldo-keto reductase family 1 member B10 Sulindac is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities. D0Z5IU DB00606 Cyclothiazide small molecule approved 2259-96-3 389.878 C14H16ClN3O4S2 P54710#Sodium/potassium-transporting ATPase subunit gamma@P00915#Carbonic anhydrase 1@Q8N1Q1#Carbonic anhydrase 13@Q9ULX7#Carbonic anhydrase 14@P00918#Carbonic anhydrase 2@P07451#Carbonic anhydrase 3@P22748#Carbonic anhydrase 4@P23280#Carbonic anhydrase 6@P43166#Carbonic anhydrase 7@Q16790#Carbonic anhydrase 9 Like other thiazides, cyclothiazide promotes water loss from the body (diuretics). It inhibits Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Cyclothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Cyclothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. D03CNS DB00607 Nafcillin small molecule approved 147-52-4 414.475 C21H22N2O5S P0A3M6#Penicillin-binding protein 2B@Q8DR59#Penicillin-binding protein 1A@Q7CRA4#Penicillin-binding protein 1b Nafcillin is a semisynthetic antibiotic substance derived from 6-amino-penicillanic acid. The drugs in this class are highly resistant to inactivation by staphylococcal penicillinase and are active against penicillinase-producing and non penicillinase-producing strains of Staphylococcus species. D0A0JH DB00608 Chloroquine small molecule approved 54-05-7 319.872 C18H26ClN3 P09210#Glutathione S-transferase A2@P01375#Tumor necrosis factor@Q9NR96#Toll-like receptor 9@Q8MU52#Glutathione S-transferase@P09429#High mobility group protein B1@P09488#Glutathione S-transferase Mu 1@Q9BYF1#Angiotensin-converting enzyme 2 Chloroquine inhibits the action of heme polymerase, which causes the buildup of toxic heme in Plasmodium species.11 It has a long duration of action as the half life is 20-60 days.10 Patients should be counselled regarding the risk of retinopathy with long term usage or high dosage, muscle weakness, and toxicity in children.19 D09EGZ DB00609 Ethionamide small molecule approved 536-33-4 166.243 C8H10N2S A0A6L8PBX8#Enoyl-[acyl-carrier-protein] reductase [NADH]@P9WIE5#Catalase-peroxidase Ethinamate is bacteriostatic against M. tuberculosis. In a study examining ethionamide resistance, ethionamide administered orally initially decreased the number of culturable Mycobacterium tuberculosis organisms from the lungs of H37Rv infected mice. Drug resistance developed with continued ethionamide monotherapy, but did not occur when mice received ethionamide in combination with streptomycin or isoniazid. D0P0HB DB00610 Metaraminol small molecule approved 54-49-9 167.205 C9H13NO2 P35348#Alpha-1A adrenergic receptor Metaraminol is a potent sympathomimetic amine that increases both systolic and diastolic blood pressure. Metaraminol is indicated for prevention and treatment of the acute hypotensive state occurring with spinal anesthesia. It is also indicated as adjunctive treatment of hypotension due to hemorrhage, reactions to medications, surgical complications, and shock associated with brain damage due to trauma or tumor. Metaraminol acts on both α1-adrenergic receptors but appears to have no effect on β-adrenergic receptors. It acts by increasing the force of the heart's pumping action as well as constricting peripheral blood vessels. D04EYC DB00611 Butorphanol small molecule approved 42408-82-2 327.4605 C21H29NO2 P41145#Kappa-type opioid receptor@P41143#Delta-type opioid receptor@P35372#Mu-type opioid receptor Butorphanol is a synthetic opioid agonist-antagonist analgesic with a pharmacological and therapeutic profile that has been well established since its launch as a parenteral formulation in 1978. The introduction of a transnasal formulation of butorphanol represents a new and noninvasive presentation of an analgesic for moderate to severe pain. This route of administration bypasses the gastrointestinal tract, and this is an advantage for a drug such as butorphanol that undergoes significant first-pass metabolism after oral administration. The onset of action and systemic bioavailability of butorphanol following transnasal delivery are similar to those after parenteral administration. Butorphanol blocks pain impulses at specific sites in the brain and spinal cord. D0X9RG DB00612 Bisoprolol small molecule approved 66722-44-9 325.443 C18H31NO4 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor Bisoprolol decreases heart rate (chronotropy), decreases contractility (inotropy), and reduces blood pressure.14,16 The results of various clinical studies indicate that bisoprolol reduces cardiovascular mortality and all-cause mortality in patients with heart failure and decreased cardiac ejection fraction (EF).3,8 D0K3ZR DB00613 Amodiaquine small molecule approved 86-42-0 355.861 C20H22ClN3O P50135#Histamine N-methyltransferase Amodiaquine, a 4-aminoquinoline similar to chloroquine in structure and activity, has been used as both an antimalarial and an anti-inflammatory agent for more than 40 years. Amodiaquine is at least as effective as chloroquine, and is effective against some chloroquine-resistant strains, although resistance to amodiaquine has been reported. The mode of action of amodiaquine has not yet been determined. 4-Aminoquinolines depress cardiac muscle, impair cardiac conductivity, and produce vasodilatation with resultant hypotension. They depress respiration and cause diplopia, dizziness and nausea. D04NQI DB05521 Telaprevir small molecule approved 402957-28-2 679.8493 C36H53N7O6 Q9Y6L6#Solute carrier organic anion transporter family member 1B1@O94956#Solute carrier organic anion transporter family member 2B1 Telaprevir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1 Label. D0X9CH DB05528 Mipomersen small molecule approved 1000120-98-8 7177.11 C230H324N67O122P19S19 Mipomersen sodium decreases the levels of apolipoprotein B (apo B), low density lipoprotein (LDL) non-high density lipoprotein-cholesterol, and total cholesterol. D08CVQ DB05541 Brivaracetam small molecule approved 357336-20-0 212.2887 C11H20N2O2 Q7L0J3#Synaptic vesicle glycoprotein 2A@Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha@Q9NY72#Sodium channel subunit beta-3@Q8IWT1#Sodium channel subunit beta-4 Brivaracetam binds SV2A with high affinity 2. SV2A is known to play a role in epileptogenesis through modulation of synaptic GABA release 3. It is thought that brivaracetam exerts its anti-epileptogenic effects through its binding to SV2A. Brivaracetam is also known to inhibit Na+ channels which may also contribute to its anti-epileptogenic action 4. D0CT4D DB05630 Sodium stibogluconate small molecule approved 16037-91-5 907.88 C12H35Na3O26Sb2 Q06AK7#DNA topoisomerase 1 The mode of action of sodium stibogluconate is not clearly understood. In vitro exposure of amastigotes to 500 mg pentavalent antimony/ml results in a greater than 50% decrease in parasite DNA, RNA protein and purine nucleoside triphosphate levels. It has been postulated that the reduction in ATP (adenosine triphosphate) and GTP (guanosine triphosphate) synthesis contributes to decreased macromolecular synthesis. DB05676 Apremilast small molecule approved 608141-41-9 460.5 C22H24N2O7S Q86V67#Phosphodiesterase isozyme 4 Apremilast reduces but does not completely inhibit various inflammatory cytokines such as IL-1α, IL-6, IL-8, IL-10 MCP-1, MIP-1β, MMP-3, and TNF-α, relieving the symptoms of psoriasis and Behcet's disease, which are caused by an increase in these inflammatory mediators.6,13 This drug has also been proven to be effective in relieving the pain associated with oral ulcers in Behcet's disease.11 D07ESC DB05812 Abiraterone small molecule approved 154229-19-3 349.509 C24H31NO P05093#Steroid 17-alpha-hydroxylase/17,20 lyase Abiraterone is associated with decreases in PSA levels, tumor shrinkage (as evaluated by RECIST criteria), radiographic regression of bone metastases and improvement in pain. Levels of adrenocorticotropic hormones increased up to 6-fold but this can be suppressed by dexamethasone. DB05990 Obeticholic acid small molecule approved 459789-99-2 420.6252 C26H44O4 Q96RI1#Bile acid receptor The activation of the FXR by obeticholic acid acts to reduce the synthesis of bile acids, inflammation, and the resulting hepatic fibrosis. This may increase the survival of patients with PBC, but to date, an association between obeticholic acid and survival in PBC has not been established.3,9 DB06016 Cariprazine small molecule approved 839712-12-8 427.41 C21H32Cl2N4O P08908#5-hydroxytryptamine receptor 1A@P41595#5-hydroxytryptamine receptor 2B@P28223#5-hydroxytryptamine receptor 2A@P70174#Histamine H1 receptor@P28335#5-hydroxytryptamine receptor 2C@P35348#Alpha-1A adrenergic receptor Cariprazine is an antipsychotic agent. In clinical trials, it reduced positive and negative symptoms in patients with schizophrenia and acute mania in patients with bipolar I disorder. In animal models, cariprazine showed therapeutic benefits against cognitive deficits, mania, and catalepsy.2 In a meta-analysis study, cariprazine was shown to improve anxiety and depressed mood in patients with psychosis.3 D05XGO DB06077 Lumateperone small molecule approved 313368-91-1 393.506 C24H28FN3O P31645#Sodium-dependent serotonin transporter@Q13224#Glutamate receptor ionotropic, NMDA 2B@P28223#5-hydroxytryptamine receptor 2A Lumateperone, also known as ITI-007, is an atypical antipsychotic that has proven to be effective in the treatment of schizophrenia.1 Lumateperone's receptor binding profile is unique, allowing it to target schizophrenia related symptoms while minimizing adverse effects.1,5 In contrast to other second generation antipsychotics such as lurasidone and brexpiprazole, lumateperone behaves as a partial agonist and as an antagonist at pre and postynaptic dopamine (D2) receptors respectively.1 DB06119 Cenobamate small molecule approved 913088-80-9 267.67 C10H10ClN5O2 The mechanism of cenobamate is unknown, however it modulates GABAA and inhibit voltage gated sodium channels.3 Cenobamate is given once daily and so it has a long duration of action.3 The therapeutic window is wide as doses of 750mg can be well tolerated.2 Patients should be counselled regarding the risk of DRESS syndrome, QT interval shortening, suicidal behavior, and neurological adverse effects.3 DU8CF6 DB06144 Sertindole small molecule approved 106516-24-9 440.941 C24H26ClFN4O P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P50406#5-hydroxytryptamine receptor 6@Q12809#Potassium voltage-gated channel subfamily H member 2@P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor Sertindole is an atypical antipsychotic at least as effective as haloperidol and risperidone in the treatment of neuroleptic-responsive schizophrenia. Sertindole improves negative symptoms, and is also effective for the treatment of neuroleptic-resistant schizophrenia. Sertindole is generally well tolerated and is associated with a low rate of extrapyramidal symptoms (EPS). D0OS6O DB06145 Spiramycin small molecule approved 24916-50-5 843.065 C43H74N2O14 Q9A1X4#50S ribosomal protein L3 The absolute bioavailability of oral spiramycin is generally within the range of 30 to 40%. After a 1 g oral dose, the maximum serum drug concentration was found to be within the range 0.4 to 1.4 mg/L. D0F5OR DB06147 Sulfathiazole small molecule approved 72-14-0 255.317 C9H9N3O2S2 Q27738#Dihydropteroate synthetase Not Available DB06148 Mianserin small molecule approved 24219-97-4 264.3648 C18H20N2 P08913#Alpha-2A adrenergic receptor@P41595#5-hydroxytryptamine receptor 2B@P35367#Histamine H1 receptor@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P41145#Kappa-type opioid receptor@P14416#D(2) dopamine receptor@P21728#D(1A) dopamine receptor Mianserin is a tetracyclic antidepressant that has antihistaminic and hypnosedative, but almost no anticholinergic, effect. It is a weak inhibitor of norepinephrine reuptake and strongly stimulates the release of norepinephrine. Interactions with serotonin receptors in the central nervous system have also been found. Its effect is usually noticeable after one to three weeks. Mianserin may cause drowsiness and hematological problems. D0R6RO DB06150 Sulfadimethoxine small molecule approved 122-11-2 310.329 C12H14N4O4S Sulfadimethoxine has been shown to be effective against streptococci, klebsiella, proteus, shigella, staphylococci, escherichia, and salmonella. DB06151 Acetylcysteine small molecule approved 616-91-1 163.195 C5H9NO3S P48637#Glutathione synthetase@Q9UPY5#Cystine/glutamate transporter@Q03154#Aminoacylase-1@O14920#Inhibitor of nuclear factor kappa-B kinase subunit beta@O15111#Inhibitor of nuclear factor kappa-B kinase subunit alpha@Q13224#Glutamate receptor ionotropic, NMDA 2B@Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@O15399#Glutamate receptor ionotropic, NMDA 2D@Q8TCU5#Glutamate receptor ionotropic, NMDA 3A Acetylcysteine is indicated for mucolytic therapy and in the management of acetaminophen overdose.14,15,16,17 It has a short duration of action as it is given every 1-8 hours depending on route of administration, and has a wide therapeutic window.14,15,16,17 Patients should be counselled regarding diluting oral solutions in cola for taste masking,7 the risk of hypersensitivity, and the risk of upper gastrointestinal hemorrhage.14,15,16,17 D06XGW DB06152 Nylidrin small molecule approved 447-41-6 299.414 C19H25NO2 P48551#Interferon alpha/beta receptor 2@Q9P0X4#Voltage-dependent T-type calcium channel subunit alpha-1I Nylidrin hydrochloride acts mainly by beta-receptor stimulation 1, 15. Beta stimulation with nylidrin has been studied and confirmed in a variety of isolated tissues from rabbits, guinea pigs, as well as dogs. This drug has been shown to dilate arterioles in skeletal muscle and to increase cardiac output in the anesthetized dog and cat as well as the unanesthetized man. An increase in cerebral blood flow and a decrease in vascular resistance has also been reported. The result of this combination of mechanisms is an improved blood supply to ischemic tissues, with minimal change in blood pressure (generally) 16. DB06153 Pizotifen small molecule approved 15574-96-6 295.44 C19H21NS P20309#Muscarinic acetylcholine receptor M3@P08913#Alpha-2A adrenergic receptor@P41595#5-hydroxytryptamine receptor 2B@P35367#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2@P18089#Alpha-2B adrenergic receptor@P28222#5-hydroxytryptamine receptor 1B Various studies have shown pizotifen to be effective in the prophylaxis of migraines in reducing the frequency and severity of vascular headaches 3. Evidence from studies in vivo and in vitro demonstrate antagonistic actions towards serotonin and histamine. Pizotifen blocks the postsynaptic 5-HT2 receptors, as supported by antagonism of several direct agonists of 5-HT receptors 5. It is an antagonist at histamine H1 receptors, and is weakly anticholinergic 9. It also binds to α1- and α2-adrenergic receptors, and dopamine receptors 9. Pizotifen elicits a minimal effect as an epinephrine or bradykinin antagonist 10. Pizotifen exhibits weak sedative properties in mouse and monkey studies, as indicated by inhibition of locomotion and potentiation of barbiturates, without changes in cardiac or respiratory rates 10. In dogs, intravenous administration of pizotifen cause rapid hypotension but was reversed to normal within 30 minutes 10. Pizotifen was shown to inhibit serotonin uptake in the isolated perfused cat spleen and, in vivo, inhibits serotonin-induced contractions in rat uterus and cat nictiating membrane 2. In contrast, pizotifen demonstrated a venoconstrictor activity in vivo when orally or intravenously administered to saphenous veins in conscious dogs 4. Pizotifen has the potential to stimulate the appetite and may cause weight gain upon treatment 2. DB06154 Pentaerythritol tetranitrate small molecule approved 78-11-5 316.1366 C5H8N4O12 P69905#Hemoglobin subunit alpha@P68871#Hemoglobin subunit beta Organic nitrate which causes systemic vasodilation, decreasing cardiovascular preload 15. D0W9TE DB06155 Rimonabant small molecule approved 168273-06-1 463.787 C22H21Cl3N4O P21554#Cannabinoid receptor 1@Q9Y2T6#G-protein coupled receptor 55 In the RIO-North America trial, 3040 patients were randomized to receive either placebo or one of two doses of rimonabant (5 mg or 20 mg per day). Patients taking 20 mg rimonabant had significant weigh loss, decrease in waist circumference, improved insulin sensitivity, and increases in HDL cholesterol, compared to patients on placebo. DB06174 Noscapine small molecule approved 128-62-1 413.4205 C22H23NO7 Q99720#Sigma non-opioid intracellular receptor 1 Not Available DB06176 Romidepsin small molecule approved 128517-07-7 540.69 C24H36N4O6S2 Q13547#Histone deacetylase 1@Q92769#Histone deacetylase 2@P56524#Histone deacetylase 4@Q9UBN7#Histone deacetylase 6@P33527#Multidrug resistance-associated protein 1 Not Available D0L7LC DB06193 Pixantrone small molecule approved 144510-96-3 325.372 C17H19N5O2 However, pixantrone is believed to have additional mechanisms of action as its potency does not correlate to the degree of double stranded DNA breaks observed. It has been postulated that this second mechanism may be pixantrone-DNA adduct formation. [1] D0Q4OW DB06196 Icatibant small molecule approved 130308-48-4 1304.54 C59H89N19O13S P30411#B2 bradykinin receptor@P15144#Aminopeptidase N Icatibant is a potent, specific, competitive, and selective peptidomimetic bradykinin beta2-receptor antagonist (pA2 = 9.04). It has a modified peptide structure, and is the first bradykinin receptor antagonist to act on the guinea-pig trachea without demonstrating agonist effects. It also inhibits aminopeptidase N (Ki = 9.1 μM). If an IV dose of 0.4 and 0.8 mg/kg was infused over 4 hours, one may observe an inhibited response to bradykinin challenge for 6 - 8 hours following completion of infusion. D04ZBT DB06201 Rufinamide small molecule approved 106308-44-5 238.1935 C10H8F2N4O Q15858#Sodium channel protein type 9 subunit alpha@P41594#Metabotropic glutamate receptor 5 At high concentrations will inhibit action of mGluR5 subtype receptors thus preventing the production of glutamate. D0MD2L DB06202 Lasofoxifene small molecule approved 180916-16-9 413.5512 C28H31NO2 P34972#Cannabinoid receptor 2@P03372#Estrogen receptor@Q92731#Estrogen receptor beta Lasofoxifene exhibits both significant estrogenic and antiestrogenic activity both in vitro and in vivo, targeting any tissues that possess ERs, such as bone, uterus, breast, blood vessels, and liver. Binding assays demonstrated high affinity of the compound for both ERα and ERβ in a tissue-dependent manner. It mimics the effects of estradiol with varying agonist and antagonist effects. D09NMD DB06203 Alogliptin small molecule approved 850649-61-5 339.3916 C18H21N5O2 P27487#Dipeptidyl peptidase 4 Peak inhibition of DPP-4 occurs within 2-3 hours after a single-dose administration to healthy subjects. The peak inhibition of DPP-4 exceeded 93% across doses of 12.5 mg to 800 mg. Inhibition of DPP-4 remained above 80% at 24 hours for doses greater than or equal to 25 mg. Alogliptin also demonstrated decreases in postprandial glucagon while increasing postprandial active GLP-1 levels compared to placebo over an 8-hour period following a standardized meal. Alogliptin does not affect the QTc interval. D0NJ5H DB06204 Tapentadol small molecule approved 175591-23-8 221.3385 C14H23NO P35372#Mu-type opioid receptor@P23975#Sodium-dependent noradrenaline transporter@P41145#Kappa-type opioid receptor@P41143#Delta-type opioid receptor@P46098#5-hydroxytryptamine receptor 3A@P31645#Sodium-dependent serotonin transporter Tapentadol is a centrally-acting synthetic analgesic that is 18 times less potent than morphine in binding mu-opioid receptors. It also increases norepinephrine concentrations in the brains of rats via inhibition of norepinephrine reuptake. Selective mu-opioid antagonists like naloxone can block analgesia from tapentadol. It also has not effect on the QT interval. DB06206 Sugammadex small molecule approved 343306-71-8 2002.12 C72H112O48S8 Not Available DB06207 Silodosin small molecule approved 160970-54-7 495.5345 C25H32F3N3O4 P35348#Alpha-1A adrenergic receptor@P25100#Alpha-1D adrenergic receptor@P35368#Alpha-1B adrenergic receptor Silodosin is an antagonist of α1-adrenoceptors. It has the highest selectivity for the α1A-adrenoceptor subtype, with a 162-fold greater affinity than α1B-adrenoceptor and about a 50-fold greater affinity than for α1D-adrenoceptor. In clinical trials, silodosin improved maximum urinary flow rate, voiding symptoms, and storage symptoms of benign prostatic hyperplasia.2,3 Following oral administration, silodosin had a rapid onset of effect in men,3 with early effects of relieving lower urinary tract symptoms occurring within two to six hours post-dose.6 DB06209 Prasugrel small molecule approved 150322-43-3 373.441 C20H20FNO3S Q9H244#P2Y purinoceptor 12 Prasugrel is a thienopyridine ADP receptor inhibitors which inhibits platelet aggregation by irreversibly binding to P2Y12 receptors. D07IRF DB06210 Eltrombopag small molecule approved 496775-61-2 442.4666 C25H22N4O4 P40238#Thrombopoietin receptor Not Available D00PEH DB06211 Doripenem small molecule approved 148016-81-3 420.504 C15H24N4O6S2 A0A0E1R3H3#Penicillin-binding protein 3@P72355#Penicillin-binding protein 4 Similar to other beta-lactam antimicrobial agents, the time that unbound plasma concentration of doripenem exceeds the MIC (T>MIC) of the infecting organism has been shown to best correlate with efficacy in animal models of infection. D03QWT DB06212 Tolvaptan small molecule approved 150683-30-0 448.941 C26H25ClN2O3 P30518#Vasopressin V2 receptor@P37288#Vasopressin V1a receptor Urine volume and fluid intake increase in a dose dependent manner which results in overall negative fluid balance in patients taking tolvaptan. Increases in serum sodium and osmolality can be observed 4-8 hours post-administration and is maintained for 24 hours. The magnitude of serum sodium and osmolality change increases with escalating doses. Furthermore, a decrease in urine osmolality and increase in free water clearance can be observed 4 hours after post-administration of tolvaptan. The affinity for V2 receptors is 29x greater than that of V1a receptors and does not have any appreciable affinity for V2 receptors. D03KZM DB06213 Regadenoson small molecule approved 313348-27-5 390.354 C15H18N8O5 P29274#Adenosine receptor A2a Regadenoson rapidly increases coronary blood flow (CBF) which is sustained for a short duration. Mean average peak velocity increased to greater than twice baseline by 30 seconds and decreased to less than twice the baseline level within 10 minutes. Myocardial uptake of the radiopharmaceutical is proportional to (CBF). Regadenoson increases blood flow in normal coronary arteries but not in stenotic (blocked) arteries. The significance of this finding is that stenotic arteries will take up less of the radiopharmaceutical than normal coronary arteries, resulting in a signal that is less intense in these areas. D0XE1C DB06215 Ferumoxytol small molecule approved 722492-56-0 231.531 Fe3O4 The pharmacodynamic effect of ferumoxytol on hematologic indexes such as Hgb (hemoglobin), serum ferritin, and TSAT (transferrin saturation) were studied and measured as primary and secondary endpoints in clinical efficacy studies 14. D06CTM DB06216 Asenapine small molecule approved 65576-45-6 401.84 C21H20ClNO5 P21728#D(1A) dopamine receptor@P08588#Beta-1 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P41595#5-hydroxytryptamine receptor 2B@P35367#Histamine H1 receptor@P18089#Alpha-2B adrenergic receptor@P35462#D(3) dopamine receptor@P07550#Beta-2 adrenergic receptor@P14416#D(2) dopamine receptor@P28222#5-hydroxytryptamine receptor 1B Asenapine is a serotonin, dopamine, noradrenaline, and histamine antagonist in which asenapine possess more potent activity with serotonin receptors than dopamine. Sedation in patients is associated with asenapine's antagonist activity at histamine receptors. Its lower incidence of extrapyramidal effects are associated with the upregulation of D1 receptors. This upregulation occurs due to asenapine's dose-dependent effects on glutamate transmission in the brain. It does not have any significant activity with muscarinic, cholinergic receptors therefore symptoms associated with anticholinergic drug activity like dry mouth or constipation are not expected to be observed. Asenapine has a higher affinity for all aforementioned receptors compared to first-generation and second-generation antipsychotics except for 5-HT1A and 5-HT1B receptors. D00JRA DB06217 Vernakalant small molecule approved 794466-70-9 349.471 C20H31NO4 Q14524#Sodium channel protein type 5 subunit alpha@P22460#Potassium voltage-gated channel subfamily A member 5@Q9UK17#Potassium voltage-gated channel subfamily D member 3@Q12809#Potassium voltage-gated channel subfamily H member 2 Vernakalant blocks currents in all phases of atrial action potential including atria-specific potassium currents (the ultra-rapid delayed rectifier and the acetylcholine dependent potassium currents) and prolongs the refractory period. It dose-dependently prolongs atrial refractoriness, prolongs AV nodal conduction and refractoriness, and slightly prolongs QRS duration without significantly affecting ventricular refractory period. Vernakalant has a high affinity to ion channels specifically involved in repolarization of atrial tissue and is thought to have a low proarrhythmic potential. D00OTL DB06218 Lacosamide small molecule approved 175481-36-4 250.2936 C13H18N2O3 Q15858#Sodium channel protein type 9 subunit alpha@Q9NY46#Sodium channel protein type 3 subunit alpha@Q9Y5Y9#Sodium channel protein type 10 subunit alpha Lacosamide therapy is correlated with a decrease in seizure frequency. It should be noted that in group analyses, dosages above 400 mg/day do not appear to result in additional benefit. D05OFX DB06228 Rivaroxaban small molecule approved 366789-02-8 435.881 C19H18ClN3O5S P00742#Coagulation factor X Rivaroxaban is an anticoagulant which binds directly to factor Xa. Thereafter, it effectively blocks the amplification of the coagulation cascade, preventing the formation of thrombus. Rivaroxaban is a unqiue anticoagulant for two reasons. First of all, it is does not involve antithrombin III (ATIII) to exert its anticoagulant effects. Secondly, it is an oral agent whereas the widely used unfractionated heparin and low molecular weight heparins are for parenteral use only. Although the activated partial thromboplastin time (aPTT) and HepTest (a test developed to assay low molecular weight heparins) are prolonged in a dose-dependant manner, neither test is recommended for the assessment of the pharmacodynamic effects of rivaroxaban. Anti-Xa activity and inhibition of anti-Xa activity monitoring is also not recommended despite being influenced by rivaroxaban. D0KG3R DB06230 Nalmefene small molecule approved 55096-26-9 339.435 C21H25NO3 P41145#Kappa-type opioid receptor@P41143#Delta-type opioid receptor@P35372#Mu-type opioid receptor Nalmefene is an opioid antagonist with no agonist activity. It works to prevent or reverse the effects of opioids, including respiratory depression, sedation, and hypotension.8 Nalmefene has a longer duration of action than naloxone, another opioid antagonist used to reverse opioid overdose.2,8 In a study of brain receptor occupancy, a 1 mg dose of nalmefene blocked over 80% of brain opioid receptors within five minutes after administration.8 D05VIL DB06237 Avanafil small molecule approved 330784-47-9 483.951 C23H26ClN7O3 O76074#cGMP-specific 3',5'-cyclic phosphodiesterase Avanafil is a strong competitive inhibitor of phosphodiesterase 5 (PDE5) with a demonstrated in vitro IC50 of 5.2 nM.5 Its inhibitory effects on PDE5 are 100-fold more potent than on PDE6 and >1000-fold more potent than on other PDE enzymes,4 meaning it is less likely to cause visual disturbances and cardiovascular adverse effects when compared with less selective PDE5 inhibitors such as sildenafil and vardenafil.5 It has a relatively quick onset of action allowing for administration as early as 15 minutes prior to sexual activity.4 D0Y5JC DB06243 Eflornithine small molecule approved 70052-12-9 182.171 C6H12F2N2O2 P11926#Ornithine decarboxylase Not Available D0X7JR DB06249 Arzoxifene small molecule approved 182133-25-1 475.6 C28H29NO4S P03372#Estrogen receptor@Q92731#Estrogen receptor beta Not Available DB06261 Hexaminolevulinate small molecule approved 140898-97-1 215.293 C11H21NO3 DB06262 Droxidopa small molecule approved 23651-95-8 213.189 C9H11NO5 P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P18825#Alpha-2C adrenergic receptor@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P00439#Phenylalanine-4-hydroxylase Droxidopa is an orally active synthetic precursor of norepinephrine that increases the deficient supply of norepinephrine in patients with NOH, thereby improving orthostatic blood pressure and alleviating associated symptoms of lightheadedness, dizziness, blurred vision, and syncope through the induction of tachycardia (increased heart rate) and hypertension. D0I3RO DB06267 Udenafil small molecule approved 268203-93-6 516.656 C25H36N6O4S O76074#cGMP-specific 3',5'-cyclic phosphodiesterase Udenafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor. D01GUS DB06268 Sitaxentan small molecule approved 184036-34-8 454.905 C18H15ClN2O6S2 P25101#Endothelin-1 receptor@P24530#Endothelin B receptor Sitaxentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Sitaxentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects. DB06274 Alvimopan small molecule approved 156053-89-3 424.5326 C25H32N2O4 P35372#Mu-type opioid receptor@P41145#Kappa-type opioid receptor@P41143#Delta-type opioid receptor Not Available D0D7KC DB06282 Levocetirizine small molecule approved 130018-77-8 388.89 C21H25ClN2O3 P70174#Histamine H1 receptor Levocetirizine is a second generation histamine H1 antagonist used to treat various allergic symptoms.2,3,4 It has a long duration of action as it is generally taken once daily, and a wide therapeutic window as animal studies show the maximal nonlethal dose is over 100x a normal dose.4 Patients are cautioned to avoid tasks that require complete alertness, avoid alertness, and use caution in patients with factors predisposing urinary retention.4 DB06287 Temsirolimus small molecule approved 162635-04-3 1030.2871 C56H87NO16 P42345#Serine/threonine-protein kinase mTOR Not Available D0ES1Q DB06288 Amisulpride small molecule approved 71675-85-9 369.479 C17H27N3O4S P34969#5-hydroxytryptamine receptor 7@P28223#5-hydroxytryptamine receptor 2A@P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor Amisulpride is a selective dopamine D2 and D3 receptor antagonist with no affinity towards other dopamine receptor subtypes. Amisulpride is an atypical antipsychotic agent that works as an antagonist at dopamine receptors in the limbic system. Since it works preferentially in the limbic system, amisulpride is less likely to be associated with extrapyramidal adverse effects than other atypical antipsychotic agents. Amisulpride has no affinity for serotonin, alpha-adrenergic, H1-histamine, cholinergic, and sigma receptors. In clinical trials, amisulpride improved reduced secondary negative symptoms, affective symptoms, and psychomotor retardation in patients with acute exacerbation of schizophrenia. Notably, amisulpride has a differential target binding profile at different doses: at low doses, amisulpride selectively binds to presynaptic dopamine autoreceptors. At high doses, it preferentially binds to post-synaptic dopamine receptors.3 This explains how amisulpride reduces negative symptoms at low doses and mediates antipsychotic effects at high doses.11 One study alluded that the antinociceptive effects of amisulpride are mediated through opioid receptor acvitation and D2 receptor antagonism. 3,5 The actions of amisulpride at opioid receptors may explain its pro-convulsant properties.5 D03ELL DB06290 Simeprevir small molecule approved 923604-59-5 749.939 C38H47N5O7S2 Q91RS4#NS3 protease D00TLP DB06292 Dapagliflozin small molecule approved 461432-26-8 408.873 C21H25ClO6 P31639#Sodium/glucose cotransporter 2 Dapagliflozin inhibits the sodium-glucose contransporter 2(SGLT2) which is primarily located in the proximal tubule of the nephron1. SGLT2 facilitates 90% of glucose resorption in the kidneys and so its inhibition allows for glucose to be excreted in the urine1. This excretion allows for better glycemic control and potentially weight loss in patients with type 2 diabetes mellitus1. D01TNW DB06335 Saxagliptin small molecule approved 361442-04-8 315.41 C18H25N3O2 P27487#Dipeptidyl peptidase 4 Post-administration of saxagliptin, GLP-1 and GIP levels rise up to 2- to 3- fold. Because it is very selective of DPP-4 inhibition, there are fewer systemic side effects. Saxagliptin inhibits DPP-4 enzyme activity for a 24-hour period. It also decreased glucagon concentrations and increased glucose-dependent insulin secretion from pancreatic beta cells. The half maximal inhibitory concentration (IC50) is 0.5 nmol/L. Saxagliptin did not prolong the QTc interval to a clinically significant degree. D0K9MY DB06401 Bazedoxifene small molecule approved 198481-32-2 470.613 C30H34N2O3 P03372#Estrogen receptor@Q92731#Estrogen receptor beta Not Available D0JY8T DB06402 Telavancin small molecule approved 372151-71-8 1755.65 C80H106Cl2N11O27P Telavancin is a semi-synthetic derivative of vancomycin, therefore the mode of bactericidal action is similar to vancomycin in which both antibiotics inhibit cell wall synthesis. Not only that, it displays concentration-dependent bactericidal action. Furthermore, telavancin is a more potent inhibitor (10-fold) of peptidoglycan synthesis and, unlike vancomycin, disrupts cell membrane integrity via its interaction with lipid II. AUC/MIC ratio best predicts the extent of in-vivo response in which the higher the ratio, the greater the bactericidal activity. The smallest ratio in which one would be able to observe no bacterial growth at 24 hours is 50. Maximal bactericidal activity is observed at a AUC/MIC ratio of 404. D0B9JO DB06403 Ambrisentan small molecule approved 177036-94-1 378.428 C22H22N2O4 P25101#Endothelin-1 receptor@P24530#Endothelin B receptor Ambrisentan 10 mg daily had no significant effect on the QTc interval, whereas a 40 mg daily dose of ambrisentan increased mean QTc at tmax by 5 ms with an upper 95% confidence limit of 9 ms. Significant QTc prolongation is not expected in patients taking ambrisentan without concomitant metabolic inhibitors. D0X5ZI DB06410 Doxercalciferol small molecule approved 54573-75-0 412.6478 C28H44O2 P11473#Vitamin D3 receptor Not Available D0G5CF DB06412 Oxymetholone small molecule approved 434-07-1 332.484 C21H32O3 P10275#Androgen receptor@P16860#Natriuretic peptides B Not Available D0Q6NZ DB06413 Armodafinil small molecule approved 112111-43-0 273.35 C15H15NO2S D0J5RN DB06414 Etravirine small molecule approved 269055-15-4 435.277 C20H15BrN6O P03366#Gag-Pol polyprotein@P03366#Gag-Pol polyprotein@Q72547#Reverse transcriptase/RNaseH Clinical trials have shown no prolongation of QT intervals on electrocardiograms after 8 days of dosing. D0BP9C DB06441 Cangrelor small molecule approved 163706-06-7 776.35 C17H25Cl2F3N5O12P3S2 Q9H244#P2Y purinoceptor 12 Not Available D09QBG DB06480 Prucalopride small molecule approved 179474-81-8 367.87 C18H26ClN3O3 Q13639#5-hydroxytryptamine receptor 4 In animal studies, prucalopride induced a dose-dependent stimulation of contractile activity in the proximal colon and inhibition of the contractility in the distal colon.4 As well it has been shown that prucalopride stimulates and amplifies giant migratory contraction which is the high-amplitude type of contraction that initiates the urge to defecate. Thus, prucalopride not only accelerates the colonic transit but also accelerates gastric emptying and small bowel transit.2 DB06589 Pazopanib small molecule approved 444731-52-6 437.518 C21H23N7O2S P17948#Vascular endothelial growth factor receptor 1@P35968#Vascular endothelial growth factor receptor 2@P35916#Vascular endothelial growth factor receptor 3@P16234#Platelet-derived growth factor receptor alpha@P09619#Platelet-derived growth factor receptor beta@P10721#Mast/stem cell growth factor receptor Kit@P22607#Fibroblast growth factor receptor 3@Q08881#Tyrosine-protein kinase ITK/TSK@P05230#Fibroblast growth factor 1@Q9UQQ2#SH2B adapter protein 3 Pazopanib is a synthetic indazolylpyrimidine and reaches steady state concentrations of >15 μg/ml. This concentration is high enough to observe maximal inhibition of VEGFR2 phosphorylation and some anti-tumour activity (concentration required to inhibit receptors is 0.01 - 0.084 μmol/L). A reduction in tumour blood flow, increased tumour apoptosis, inhibition of tumour growth, reduction in tumour interstitial fluid pressure, and hypoxia in cancer cells can be observed in patients receiving treatment. DB06590 Ceftaroline fosamil small molecule approved 229016-73-3 684.67 C22H21N8O8PS4 The time that unbound plasma concentration of ceftaroline exceeds the minimum inhibitory concentration (MIC) of the infecting organism has been shown to best correlate with efficacy in a neutropenic murine thigh infection model with S. aureus and S. pneumoniae. DB06594 Agomelatine small molecule approved 138112-76-2 243.301 C15H17NO2 P28335#5-hydroxytryptamine receptor 2C@P48039#Melatonin receptor type 1A@P49286#Melatonin receptor type 1B Agomelatine resynchronises circadian rhythms in animal models of delayed sleep phase syndrome and other circadian rhythm disruptions. It increases noradrenaline and dopamine release specifically in the frontal cortex and has no influence on the extracellular levels of serotonin. Agomelatine has shown an antidepressant-like effect in animal depression models, (learned helplessness test, despair test, and chronic mild stress) circadian rhythm desynchronisation, and in stress and anxiety models. In humans, agomelatine has positive phase shifting properties; it induces a phase advance of sleep, body temperature decline and melatonin onset. Controlled studies in humans have shown that agomelatine is as effective as the SSRI antidepressants paroxetine and sertraline in the treatment of major depression D0Y8UB DB06595 Midostaurin small molecule approved 120685-11-2 570.649 C35H30N4O4 P17252#Protein kinase C alpha type@P35968#Vascular endothelial growth factor receptor 2@P16234#Platelet-derived growth factor receptor alpha@P09619#Platelet-derived growth factor receptor beta@P36888#Receptor-type tyrosine-protein kinase FLT3@P10721#Mast/stem cell growth factor receptor Kit It targets multiple WT and mutated kinases that, when activated, constitutively stimulate aberrant signalling cascades that lead to malignancies such as AML and ASM. Alternative pharmacodynamic effect of midostaurin in prolonging QTc intervals was not clinically significant in patients with advanced SM or AML when compared to placebo. Midostaurin is therapeutically beneficial as a combination therapy for patients undergoing chemotherapy. D07NVU DB06603 Panobinostat small molecule approved 404950-80-7 349.434 C21H23N3O2 Q13547#Histone deacetylase 1@Q92769#Histone deacetylase 2@O15379#Histone deacetylase 3@P56524#Histone deacetylase 4@Q9UQL6#Histone deacetylase 5@Q9UBN7#Histone deacetylase 6@Q8WUI4#Histone deacetylase 7@Q9BY41#Histone deacetylase 8 Not Available D0E3SH DB06605 Apixaban small molecule approved 503612-47-3 459.4971 C25H25N5O4 P00742#Coagulation factor X Apixaban selectively inhibits factor Xa in its free and bound forms, independant of antithrombin IIILabel. Apixaban also inhibits prothrominaseLabel. These effects prevent the formation of a thrombusLabel. D0I5HF DB06608 Tafenoquine small molecule approved 106635-80-7 463.501 C24H28F3N3O3 In vitro studies have shown that tafenoquine presents an average 50% inhibitory concentration of 0.436 mcg against blood stages of seven strains of P. falciparum. In chloroquine-resistant P. falciparum strains the IC50 of tafenoquine was greater when compared with primaquine and it ranged from 0.5 to 33.1 mcg. In studies evaluating the transmission-blocking activity of tafenoquine against the sporogonic stage of P. vivax, it was showed a reduced transmission at doses higher than 25 mg/kg.2 D07TWN DB06614 Peramivir small molecule approved 330600-85-6 328.4072 C15H28N4O4 P03472#Neuraminidase@P27907#Neuraminidase Not Available D0P2IW DB06616 Bosutinib small molecule approved 380843-75-4 530.446 C26H29Cl2N5O3 P11274#Breakpoint cluster region protein@P00519#Tyrosine-protein kinase ABL1@P07948#Tyrosine-protein kinase Lyn@P08631#Tyrosine-protein kinase HCK@P12931#Proto-oncogene tyrosine-protein kinase Src@P24941#Cyclin-dependent kinase 2@Q02750#Dual specificity mitogen-activated protein kinase kinase 1@P36507#Dual specificity mitogen-activated protein kinase kinase 2@Q9Y2U5#Mitogen-activated protein kinase kinase kinase 2@Q13555#Calcium/calmodulin-dependent protein kinase type II subunit gamma Not Available D0OB0F DB06626 Axitinib small molecule approved 319460-85-0 386.47 C22H18N4OS P35916#Vascular endothelial growth factor receptor 3@P17948#Vascular endothelial growth factor receptor 1@P35968#Vascular endothelial growth factor receptor 2 D01ZRI DB06636 Isavuconazonium small molecule approved 742049-41-8 717.77 C35H35F2N8O5S Not Available DB06637 Dalfampridine small molecule approved 504-24-5 94.1145 C5H6N2 Q09470#Potassium voltage-gated channel subfamily A member 1@Q9UK17#Potassium voltage-gated channel subfamily D member 3@P22001#Potassium voltage-gated channel subfamily A member 3 Dalfampridine is a board-spectrum lipophillic potassium channel blocker and binds favourably to the open state than closed state of the potassium channel in the CNS. Its pharmacological target are the potassium channels exposed in MS patients. Does not prolong the QTc interval. D08YIN DB06654 Safinamide small molecule approved 133865-89-1 302.349 C17H19FN2O2 P27338#Amine oxidase [flavin-containing] B Not Available D0TV6I DB06663 Pasireotide small molecule approved 396091-73-9 1047.2062 C58H66N10O9 D0TV0C DB06684 Vilazodone small molecule approved 163521-12-8 441.5249 C26H27N5O2 P31645#Sodium-dependent serotonin transporter@P08908#5-hydroxytryptamine receptor 1A Vilazodone increases serotonin levels in the brain by inhibiting the reuptake of serotonin while acting as a partial agonist on serotonin-1A receptorsLabel,1,3. Due to this activity vilazodone has sometimes been referred to as a selective partial agonist and reuptake inhibitor (SPARI)Label,3. D0X6BV DB06689 Ethanolamine oleate small molecule approved 2272-11-9 343.5444 C20H41NO3 P00748#Coagulation factor XII When injected intravenously, ethanolamine oleate acts primarily by irritation of the intimal endothelium of the vein and produces a sterile dose-related inflammatory response. This results in fibrosis and possible occlusion of the vein. Ethanolamine oleate also rapidly diffuses through the venous wall and produces a dose-related extravascular inflammatory reaction. D0O1PH DB06690 Nitrous oxide small molecule approved 10024-97-2 44.0128 N2O Not Available D0O8DI DB06691 Mepyramine small molecule approved 91-84-9 285.384 C17H23N3O P70174#Histamine H1 receptor Not Available D08JZS DB06694 Xylometazoline small molecule approved 526-36-3 244.3752 C16H24N2 P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor@P18825#Alpha-2C adrenergic receptor Xylometazoline is a sympathomimetic agent that causes vasoconstriction of the nasal mucosa. In one study comprising subjects with nasal congestion associated with the common cold, the median time of onset of subjective relief of nasal congestion was about 1.7 minutes and the time of subjective peak relief of nasal congestion was 30 minutes.2 Previous studies reported rebound swelling, rebound nasal congestion, rhinitis medicamentosa, and shorter duration of decongestant effect from the long-term use of xylometazoline in healthy volunteers, suggesting that the drug is most effective if used temporarily.2,3 D0Y4DY DB06695 Dabigatran etexilate small molecule approved 211915-06-9 627.7332 C34H41N7O5 P00734#Prothrombin Dabigatran etexilate is a double prodrug that is hydrolyzed to the active dabigatran by intestinal and hepatic carboxylesterases.12,13,14 Dabigatran is a reversible competitive thrombin inhibitor that directly inhibits the conversion by thrombin of fibrinogen to fibrin, impairing the clotting process and acting as an anticoagulant.4,7,8,18,19 Dabigatran use prolongs coagulation markers such as the activated partial thromboplastin time (aPTT), ecarin clotting time (ECT), thrombin time (TT), and dilute thrombin time (dTT), but not the international normalized ratio (INR), which cannot be used in this context as it can in warfarin monitoring.18,19 D0KI5R DB06697 Artemether small molecule approved 71963-77-4 298.3746 C16H26O5 In the body, artemether is metabolized into the active metabolite metabolite dihydroartemisinin. The drug works against the erythrocytic stages of P. falciparum by inhibiting nucleic acid and protein synthesis. Artemether is administered in combination with lumefantrine for improved efficacy. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thought that artemether provides rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites. D0M9BW DB06698 Betahistine small molecule approved 5638-76-6 136.1943 C8H12N2 P70174#Histamine H1 receptor@Q9Y5N1#Histamine H3 receptor Through its actions on the histamine receptors, betahistine provides relief from vertigo associated with Ménière's disease.3,5,11 DB06699 Degarelix small molecule approved 214766-78-6 1632.29 C82H103ClN18O16 P30968#Gonadotropin-releasing hormone receptor Degarelix is a synthetic derivative of GnRH decapeptide, the ligand of the GnRH receptor. Gonadotropin and androgen production result from the binding of endogenous GnRH to the GnRH receptor. Degarelix antagonizes the GnRH receptor which in turn blocks the release of LH and FSH from the pituitary. LF and FSH decreases in a concentration-dependent manner. The reduction in LH leads to a decrease in testosterone release from the testes. D0Y7KH DB06700 Desvenlafaxine small molecule approved 93413-62-8 263.3752 C16H25NO2 P23975#Sodium-dependent noradrenaline transporter@P31645#Sodium-dependent serotonin transporter@Q01959#Sodium-dependent dopamine transporter Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor3,4,Label. It lacks significant activity on muscarinic-cholinergic, H1-histaminergic, or α1-adrenergic receptors in vitro. Desvenlafaxine does not appear to exert activity against calcium, chloride, potassium and sodium ion channels and also lacks monoamine oxidase (MAO) inhibitory activity4. It was also shown to lack significant activity again the cardiac potassium channel, hERG, in vitro6. Compared to other SNRIs, desvenlafaxine undergoes simple metabolism, has a low risk of drug-drug interactions and does not have to be extensively titrated to reach a therapeutic doseLabel. D0O3FG DB06701 Dexmethylphenidate small molecule approved 40431-64-9 233.3062 C14H19NO2 Q01959#Sodium-dependent dopamine transporter@P23975#Sodium-dependent noradrenaline transporter@P31645#Sodium-dependent serotonin transporter Dexmethylphenidate is the d-enantiomer of methylphenidateLabel. This enantiomer is more pharmacologically active than the racemic mixture and may block norepinephrine and dopamine reuptake in synapsesLabel. DB06702 Fesoterodine small molecule approved 286930-02-7 411.5769 C26H37NO3 P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P08912#Muscarinic acetylcholine receptor M5 In-vivo the fesoteridine prodrug is broken down into its active metabolite, 5-hydroxymethyl tolterodine (5-HMT), by plasma esterases. The 5-hydroxymethyl metabolite, which exhibits an antimuscarinic activity. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors. Therefore, acting as a competitive muscarinic receptor antagonist, fesoterodine ultimately acts to decrease the detrusor pressure by its muscarinic antagonism, thereby decreasing bladder contraction and consequently, the urge to urinate. DB06703 Gadobutrol small molecule approved 770691-21-9 604.72 C18H31GdN4O9 Even at low concentrations Gadobutrol can lead to distinct shortening of relaxation times of protons in plasma. At physiological conditions (pH=7, temperature=37°C), and 1.5T, the relaxivity (r1) is 5.2L/(mmol·sec) based on the relaxation times (T1), while the relativity (r2) is 6.1L/(mmol·sec) based on relaxation times (T2). D0P1IZ DB06704 Iobenguane small molecule approved 80663-95-2 275.0896 C8H10IN3 AdreView is a diagnostic radiopharmaceutical which contains a small quantity of iobenguane that is not expected to produce a pharmacodynamic effect. Patients with renal insufficiency may experience increased radiation exposure and impaired imaging results. DB06705 Gadofosveset trisodium small molecule approved 193901-90-5 957.87 C33H38GdN3Na3O14P Gadofosveset causes signal enhancement by shortening the T1 of water molecules that interact with it. The contrast agent complex's rotation rate is the primary factor determining the magnitude of relaxation enhancement. This relaxation enhancement increase only occurs when bound to human serum albumin. DB06706 Isometheptene small molecule approved 503-01-5 141.2539 C9H19N P35348#Alpha-1A adrenergic receptor@Q05940#Synaptic vesicular amine transporter Isometheptene Mucate is an indirect-acting sympathomimetic. Due to its vasoconstricting properties, Isometheptene Mucate is used for the treatment of acute migraine attacks, usually in combination with other analgeics. It can also displace catecholamines from vesicles inside the neuron leading to the sympathetic responses it is known for. DB06707 Levonordefrin small molecule approved 829-74-3 183.2044 C9H13NO3 P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Levonordefrin is a sympathomimetic amine used as a vasoconstrictor in local anesthetic solutions. It has pharmacologic activity similar to that of Epinephrine but it is more stable than Epinephrine. In equal concentrations, Levonordefrin is less potent than Epinephrine in raising blood pressure, and as a vasoconstrictor. DB06708 Lumefantrine small molecule approved 82186-77-4 528.94 C30H32Cl3NO Lumefantrine is a blood schizonticide active against erythrocytic stages of Plasmodium falciparum. It is thought that administration of lumefantrine with artemether results in cooperate antimalarial clearing effects. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thus thought to provide rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites. D06MQM DB06709 Methacholine small molecule approved 55-92-5 160.234 C8H18NO2 P20309#Muscarinic acetylcholine receptor M3@P08172#Muscarinic acetylcholine receptor M2 DB06710 Methyltestosterone small molecule approved 58-18-4 302.451 C20H30O2 P03372#Estrogen receptor@P10275#Androgen receptor Testosterone is a steroid hormone from the androgen group. Testosterone is primarily secreted from the testes of males. In females, it is produced in the ovaries, adrenal glands and by conversion of adrostenedione in the periphery. It is the principal male sex hormone and an anabolic steroid. In both males and females, it plays key roles in health and well-being. Examples include enhanced libido, energy, immune function, and protection against osteoporosis. On average, the adult male body produces about twenty times the amount of testosterone than an adult female's body does. D0Z1XD DB06711 Naphazoline small molecule approved 835-31-4 210.2744 C14H14N2 P08913#Alpha-2A adrenergic receptor@P35348#Alpha-1A adrenergic receptor Naphazoline is a sympathomimetic alpha adrenergic agonist that acts to vasoconstrict nasal or ocular arterioles, resulting in reduced congestion at the site of administration6,7. D0O6IZ DB06712 Nilvadipine small molecule approved 75530-68-6 385.3707 C19H19N3O6 Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@P54289#Voltage-dependent calcium channel subunit alpha-2/delta-1@Q08289#Voltage-dependent L-type calcium channel subunit beta-2@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@Q8IZS8#Voltage-dependent calcium channel subunit alpha-2/delta-3@O95180#Voltage-dependent T-type calcium channel subunit alpha-1H@Q9P0X4#Voltage-dependent T-type calcium channel subunit alpha-1I Nilvadipine is similar to other dihydropyridines including amlodipine, felodipine, isradipine, and nicardipine. Nilvadipine is used to treat Prinzmetal's angina, hypertension, and other vascular disorders such as Raynaud's phenomenon. By blocking the calcium channels, Nifedipine inhibits the spasm of the coronary artery and dilates the systemic arteries, results in a increase of myocardial oxygen supply and a decrease in systemic blood pressure. DB06713 Norelgestromin small molecule approved 53016-31-2 327.468 C21H29NO2 P06401#Progesterone receptor@P02768#Serum albumin@P10275#Androgen receptor Norelgestromin is used for contraception and menopausal hormonal therapy transdermally or in combination with ethinyl estradiol as a vaginal ring. Norelgestromin, in combination with ethinyl estradiol inhibits ovulation by suppressing gonadotropins. DB06714 Propylhexedrine small molecule approved 101-40-6 155.2804 C10H21N Q05940#Synaptic vesicular amine transporter@Q96RJ0#Trace amine-associated receptor 1 Like other monoamine releasing stimulants propylhexedrine is active as a norepinephrine and dopamine releaser in the central nervous system. The acute effects of the drug closely resemble the physiological and psychological effects of an epinephrine-provoked fight-or-flight response, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). D03DVJ DB06715 Potassium Iodide small molecule approved 7681-11-0 166.0028 IK It works in the thyroid gland. By inhibiting thyroid hormone synthesis and release, thyroid gland vascularity is reduced, thyroid gland tissue becomes firmer, thyroid cell size is reduced, follicular colloid reaccumulates, and bound iodine levels increase. As a protectant following radiation exposure, KI blocks the uptake of radioactive iodine isotopes by the thyroid gland thereby minimizing the risk of radiation-induced thyroid neoplasms. DB06716 Fospropofol small molecule approved 258516-89-1 288.2766 C13H21O5P P47870#Gamma-aminobutyric acid receptor subunit beta-2@P28472#Gamma-aminobutyric acid receptor subunit beta-3 Fospropofol is a prodrug of propofol, a sedative hypnotic drug. Unlike propofol, fospropofol is water soluble and can be administered in an aqueous solution. 1.86 mg of fospropofol is the molar equivalent for 1mg of propofol. DB06717 Fosaprepitant small molecule approved 172673-20-0 614.4066 C23H22F7N4O6P ethasone and inhibits both the acute and delayed phases of cisplatin induced emesis. DB06718 Stanozolol small molecule approved 10418-03-8 328.4916 C21H32N2O P10275#Androgen receptor Stanozolol is a synthetic anabolic-androgenic steroid (AAS), which promotes cell growth (anabolism) and development/maintenance of masculine characteristics (androgenism). D08QKJ DB06723 Aluminum hydroxide small molecule approved 21645-51-2 78.0036 AlH3O3 Gastric-peptic disease occurs as a result of an imbalance between protective factors, such as mucus, bicarbonate, and prostaglandin secretion, and aggressive factors, such as hydrochloric acid, pepsin, and Helicobacter pylori (H. pylori). Antacids work by restoring acid-base balance, attenuating the pepsin activity and increasing bicarbonate and prostaglandin secretion. DB06724 Calcium carbonate small molecule approved 471-34-1 100.087 CCaO3 Gastric-peptic disease occurs as a result of an imbalance between protective factors, such as mucus, bicarbonate, and prostaglandin secretion, and aggressive factors, such as hydrochloric acid, pepsin, and Helicobacter pylori (H. pylori). Antacids work by restoring acid-base balance, attenuating the pepsin activity and increasing bicarbonate and prostaglandin secretion. The acid-neutralizing capacity of calcium carbonate is 58 mEq/15 ml. DB06725 Lornoxicam small molecule approved 70374-39-9 371.81 C13H10ClN3O4S2 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Lornoxicam is a non-steroidal anti-inflammatory drug (NSAID) that belongs to the oxicam class. As with other NSAIDS, lornoxicam is a potent inhibitor of the cyclooxgenase enzymes, which are responsible for catalyzing the formation of prostaglandins (act as messenger molecules in the process of inflammation) and thromboxane from arachidonic acid. Unlike some NSAIDS, lornoxicam's inhibition of cyclooxygenase does not lead to an increase in leukotriene formation, meaning that arachidonic acid is not moved to the 5-lipoxygenase cascade, resulting in the minimization of the risk of adverse events. D0UL2L DB06729 Sulfaphenazole small molecule approved 526-08-9 314.362 C15H14N4O2S P0AC13#Dihydropteroate synthase Not Available D0A4YE DB06736 Aceclofenac small molecule approved 89796-99-6 354.18 C16H13Cl2NO4 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Aceclofenac is a NSAID that inhibits both isoforms of COX enzyme, a key enzyme involved in the inflammatory cascade. COX-1 enzyme is a constitutive enzyme involved in prostacyclin production and protective functions of gastric mucosa whereas COX-2 is an inducible enzyme involved in the production of inflammatory mediators in response to inflammatory stimuli. Aceclofenac displays more selectivity towards COX-2 (IC50 of 0.77uM) than COX-1 (IC50 of >100uM), which promotes its gastric tolerance compared to other NSAIDs. The primary metabolite, 4'-hydroxyaceclofenac, also minimally inhibits COX-2 with IC50 value of 36uM 2. Although the mode of action of aceclofenac is thought to mainly arise from the inhibition of synthesis of prostaglandins (PGE2), aceclofenac also inhibits the production of inflammatory cytokines, interleukins (IL-1β, IL-6), and tumor necrosis factors (TNF) 1,2. It is also reported that aceclofenac also affects the cell adhesion molecules from neutrophils 8. Aceclofenac also targets the synthesis of glycosaminoglycan and mediates chrondroprotective effects 1. D0T8VY DB06742 Ambroxol small molecule approved 18683-91-5 378.108 C13H18Br2N2O Not Available D03DSR DB06751 Drotaverine small molecule approved 14009-24-6 397.5072 C24H31NO4 P27815#cAMP-specific 3',5'-cyclic phosphodiesterase 4A@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A Drotaverine is an e spasmolytic agent with a relaxing effect on smooth muscles. It works to relieve visceral spasms and improve cervical dilation. In vitro, drotaverine mediated cytostatic effects on several human tumor cell lines and nonmalignant mouse fibroblasts.5 Drotaverine may have minor allosteric calcium channel blocking properties: in vitro, drotaverine behaves like voltage-dependent L-type calcium channel blockers.8 D06XAE DB06753 Triclofos small molecule approved 306-52-5 229.37 C2H4Cl3O4P Not Available DB06755 Beta carotene small molecule approved 7235-40-7 536.888 C40H56 Oral administration of beta-carotene increases the serum concentration of beta-carotene by 60% but it does not change the concentration found in the heart, liver or kidneys.5 In vitro studies in hepatocytes have shown that beta-carotene ameliorates oxidative stress, enhances antioxidant activity and decreases apoptosis.7 DB06756 Glycine betaine small molecule approved 107-43-7 117.1463 C5H11NO2 P10415#Apoptosis regulator Bcl-2 DB06757 Manganese small molecule approved 7439-96-5 54.938 Mn P50213#Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial@P51553#Isocitrate dehydrogenase [NAD] subunit gamma, mitochondrial@Q15750#TGF-beta-activated kinase 1 and MAP3K7-binding protein 1@P05089#Arginase-1@P02787#Serotransferrin Not Available DB06762 Pinacidil small molecule approved 60560-33-0 245.33 C13H19N5 Not Available D02KMO DB06764 Tetryzoline small molecule approved 84-22-0 200.285 C13H16N2 P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Tetryzoline is a sympathomimetic amine and an alpha-adrenergic agonist with vasoconstricting and decongestant properties. It works by constricting the smaller arterioles of the nasal passages 13 and conjunctival blood vessels to ameliorate allergic rhinitis, nasal congestion, and ocular irritation.3 Tetryzoline is known to cross the blood-brain barrier to work on alpha-2 adrenoceptors and imidazole receptors,3 causing effects like hypotension, bradycardia, analgesia, hypothermia, sedation, and hypnosis.3 DB06766 Alcaftadine small molecule approved 147084-10-4 307.3895 C19H21N3O P70174#Histamine H1 receptor Following bilateral topical ocular administration of alcaftadine ophthalmic solution, 0.25%, the mean plasma Cmax of alcaftadine was approximately 60 pg/mL and the median Tmax occurred at 15 minutes. Plasma concentrations of alcaftadine were below the lower limit of quantification (10 pg/mL) by 3 hours after dosing. The mean Cmax of the active carboxylic acid metabolite was approximately 3 ng/mL and occurred at 1 hour after dosing. Plasma concentrations of the carboxylic acid metabolite were below the lower limit of quantification (100 pg/mL) by 12 hours after dosing. D0O7JW DB06767 Ammonium chloride small molecule approved 12125-02-9 53.491 ClH4N Systemic acidifier. In liver ammonium chloride is converted into urea with the liberation of hydrogen ions ( which lowers the pH) and chloride. D06WEK DB06768 Ammonium lactate small molecule approved 515-98-0 107.1085 C3H9NO3 Lactic acid is an alpha-hydroxy acid. It is a normal constituent of tissues and blood. The alpha-hydroxy acids (and their salts) may act as humectants when applied to the skin. This property may influence hydration of the stratum corneum. In addition, lactic acid, when applied to the skin, may act to decrease corneocyte cohesion. D08QGD DB06769 Bendamustine small molecule approved 16506-27-7 358.263 C16H21Cl2N3O2 No mean changes in QTc interval greater than 20 milliseconds were detected up to one hour post-infusion. DB06770 Benzyl alcohol small molecule approved 100-51-6 108.1378 C7H8O Not Available D05OIS DB06771 Besifloxacin small molecule approved 141388-76-3 393.84 C19H21ClFN3O3 P72525#DNA topoisomerase 4 subunit A Besifloxacin tear concentrations were higher than MIC90 (minimum inhibitory concentration) values for common bacterial pathogens and sustained for 24 hours or longer. Mean residence time in the conjunctiva was 4.7 hours. D00TRV DB06772 Cabazitaxel small molecule approved 183133-96-2 835.9324 C45H57NO14 P68366#Tubulin alpha-4A chain@Q9H4B7#Tubulin beta-1 chain Cabaitaxel has anti-tumour properties and is effective against docetaxel-sensitive and -insensitive tumours. D02HSB DB06774 Capsaicin small molecule approved 404-86-4 305.4119 C18H27NO3 Q8NER1#Transient receptor potential cation channel subfamily V member 1@Q99623#Prohibitin-2 Capsaicin is a TRPV1 receptor agonist. TRPV1 is a trans-membrane receptor-ion channel complex activated by temperatures higher than 43 degrees Celsius, pH lower than 6, and endogenous lipids. When activated by a combination of these factors, the channel can transiently open and initiate depolarization due to the influx of calcium and sodium ions. Because TRPV1 is commonly expressed in A-delta and mostly C fibers, depolarization results in action potentials which send impulses to the brain and spinal cord. These impulses result in capsaicin effects of warming, tingling, itching, stinging, or burning. Capsaicin also causes more persistent activation of these receptors compared to the environmental agonists, resulting in a loss of response to many sensory stimuli, described as "defunctionalization". Capsaicin is associated with many enzymatic, cytoskeletal, and osmotic changes, as well as disruption of mitochondrial respiration, impairing nociceptor function for extended periods of time. D0U5CE DB06775 Carglumic acid small molecule approved 1188-38-1 190.154 C6H10N2O5 P31327#Carbamoyl-phosphate synthase [ammonia], mitochondrial The median Tmax of Carbaglu was 3 hours (range: 2-4). The daily dose of carglumic acid ranges from 100 to 250 mg/kg and this does are normally adjusted to maintain normal plasma levels of ammonia. D0Z0MG DB06777 Chenodeoxycholic acid small molecule approved 474-25-9 392.572 C24H40O4 Q96RI1#Bile acid receptor@O75469#Nuclear receptor subfamily 1 group I member 2@Q8TDU6#G-protein coupled bile acid receptor 1@P52895#Aldo-keto reductase family 1 member C2 It acts by reducing levels of cholesterol in the bile, helping gallstones that are made predominantly of cholesterol to dissolve. Chenodeoxycholic acid is ineffective with stones of a high calcium or bile acid content. DB06778 Cupric sulfate small molecule approved 7758-98-7 159.609 CuO4S DB06780 Desoxycorticosterone acetate small molecule approved 56-47-3 372.505 C23H32O4 P08235#Mineralocorticoid receptor Not Available DB06781 Difluprednate small molecule approved 23674-86-4 508.5515 C27H34F2O7 P04150#Glucocorticoid receptor Difluprednate is a corticosteroid used as an anti-inflammatory steroidal drug used primarily in ocular surgery. D01ZOG DB06782 Dimercaprol small molecule approved 59-52-9 124.225 C3H8OS2 P05067#Amyloid beta A4 protein Due to its oily nature, dimercaprol is not absorbed orally and its administration requires a deep intra-muscular injection that is extremely painful and allergenic. It was found to mobilize and relocate lead to the brain, increasing its neurotoxic effects. Despite that fact that dimercaprol increases cadmium excretion, there is an associated increase in kidney cadmium concentration. Because of this, dimercaprol must be avoided in patients with cadmium toxicity. D0X2IE DB06783 Prussian blue small molecule approved 14038-43-8 859.239 C18Fe7N18 D0M3TM DB06784 Gallium citrate Ga-67 small molecule approved 41183-64-6 256.0279 C6H5GaO7 It has been reported in the scientific literature that following intravenous injection, the highest tissue concentration of gallium Ga-67 - other than tumors and sites of infection - is the renal cortex. After the first day, the maximum concentration shifts to bone and lymph nodes and after the first week, to liver and spleen. Gallium Ga-67 is excreted relatively slowly from the body. The average whole body retention is 65 percent after seven days, with 26 percent having been excreted in the urine and 9 percent in the stools. DB06785 Ganirelix small molecule approved 124904-93-4 1570.35 C80H113ClN18O13 D00RJJ DB06786 Halcinonide small molecule approved 3093-35-4 454.96 C24H32ClFO5 Q99835#Smoothened homolog D06IIB DB06787 Hexocyclium small molecule approved 6004-98-4 317.496 C20H33N2O P20309#Muscarinic acetylcholine receptor M3@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P08173#Muscarinic acetylcholine receptor M4 Hexocyclium reduces gastrointesitinal motility and gastric acid secretion 2,3. DB06788 Histrelin small molecule approved 76712-82-8 1443.632 C70H94N18O16 P30968#Gonadotropin-releasing hormone receptor Histrelin inhibits gonadotropin secretion through the reversible down-regulation of gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland and desensitization of the pituitary gonadotropes.6,8 In pediatric patients with central precocious puberty (CPP), long-term treatment with histrelin acetate suppresses the luteinizing hormone (LH) response to GnRH, causing LH levels to decrease to prepubertal levels within one month of treatment.6 This reduces ovarian and testicular steroidogenesis and slows down linear growth velocity, improving the chance of attaining predicted adult height.6 When given orally, histrelin acetate is not active.8 D0O7DG DB06789 Hydroxyprogesterone caproate small molecule approved 630-56-8 428.6041 C27H40O4 P06401#Progesterone receptor No specific pharmacodynamic studies have been performed to assess hydroxyprogesterone caproate injections. (4) However, the mechanism of action is likely related to increased interaction between progesterone and progesterone receptors. (5) DB06791 Lanreotide small molecule approved 108736-35-2 1096.33 C54H69N11O10S2 P30874#Somatostatin receptor type 2@P35346#Somatostatin receptor type 5 Lanreotide exhibits antisecretory effects through cAMP suppression, and activation of ion currents such as K+ and Ca2+ which leads to hyperpolarization of the membrane and inhibition of Ca2+ mediated depolarization. Furthermore, through direct and indirect mechanisms, Lanreotide has potent antiproliferative effects. DB06792 Lanthanum carbonate small molecule approved 587-26-8 457.835 C3La2O9 In vitro studies have shown that lanthanum binds phosphate in the physiologically relevant pH range of 3 to 7. In simulated gastric fluid, lanthanum binds approximately 97% of the available phosphate at pH 3-5 and 67% at pH 7, when lanthanum is present in a two-fold molar excess to phosphate. Bile acids have not been shown to affect the phosphate binding affinity of lanthanum. In order to bind dietary phosphate, lanthanum carbonate must be administered with or immediately after meals. D0H1LO DB06794 Lodoxamide small molecule approved 53882-12-5 311.63 C11H6ClN3O6 Lodoxamide is a mast cell stabilizer that inhibits the in vivo Type 1 immediate hypersensitivity reaction. Lodoxamide therapy inhibits the increases in cutaneous vascular permeability that are associated with reagin or IgE and antigen-mediated reactions. D0OG3K DB06795 Mafenide small molecule approved 138-39-6 186.232 C7H10N2O2S P23280#Carbonic anhydrase 6 Not Available DB06796 Mangafodipir small molecule approved 155319-91-8 691.382 C22H30MnN4O14P2 Manganese (II) metals exhibit paramagnetic properties that increases contrast between normal liver parenchyma and metastatic liver lesions after uptake into the hepatic or pancreatic parencyma. They serve to increase the signal intensity of liver or pancreas tissue. Enhancement in both organs is near maximal for up to approximately 4 hours after the end of administration. Lesion-related enhancement of certain types of lesions, such as liver metastases and hepatocellular carcinomas, may be detectable for up to 24 hours 8. DB06797 Mebutamate small molecule approved 64-55-1 232.2768 C10H20N2O4 Not Available D02KBD DB06799 Methenamine small molecule approved 100-97-0 140.1863 C6H12N4 Ingestion of a 1-gram dose of methenamine hippurate produces antibacterial activity in the urine within 1/2 hour. Administration of 1 g twice daily produces continuous antibacterial activity in the urine. D02LJR DB06800 Methylnaltrexone small molecule approved 916055-93-1 356.441 C21H26NO4 P35372#Mu-type opioid receptor@P41145#Kappa-type opioid receptor Use of opioids induces slowing of gastrointestinal motility and transit. Following remifentanil administration, the methylnaltrexone and placebo groups showed no change in pupiliary constriction while the naloxone group showed a marked change over the time interval tested. DB06802 Nepafenac small molecule approved 78281-72-8 254.2839 C15H14N2O2 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Low but quantifiable plasma concentrations of nepafenac and amfenac were observed in the majority of subjects 2 and 3 hours postdose, respectively, following bilateral topical ocular TID dosing of nepafenac ophthalmic suspension, 0.1%. The mean steady-state Cmax for nepafenac and for amfenac were 0.310 ± 0.104 ng/ml and 0.422 ± 0.121 ng/ml, respectively, following ocular administration. D02IHW DB06803 Niclosamide small molecule approved 50-65-7 327.12 C13H8Cl2N2O4 Niclosamide is an antihelminth used against tapeworm infections. It may act by the uncoupling of the electron transport chain to ATP synthase. The disturbance of this crucial metabolic pathway prevents creation of adenosine tri-phosphate (ATP), an essential molecule that supplies energy for metabolism. D0J9ZR DB06804 Nonoxynol-9 small molecule approved 26027-38-3 616.8235 C33H60O10 Not Available D01TQR DB06807 Phenyl aminosalicylate small molecule approved 133-11-9 229.235 C13H11NO3 Not Available DB06809 Plerixafor small molecule approved 110078-46-1 502.782 C28H54N8 P61073#C-X-C chemokine receptor type 4 Plerixafor is a bicyclam derivative that antagonizes CXCR4 by binding to three acidic residues in the ligand-binding pocket: Asp171, Asp262, and Glu288. Blood levels of CD34+ cells peaked at 9 hours after administration of 0.24 mg/kg plerixafor in healthy subjects. In patients that have non-Hodgkin’s lymphoma or multiple myeloma, blood levels of CD34+ peaked at 6 hours. In combination with a G-CSF, circulating CD34+ cells in the peripheral blood peaked at 9-14 hours. D0L5RW DB06810 Plicamycin small molecule approved 18378-89-7 1085.1454 C52H76O24 Plicamycin is lethal to Hela cells in 48 hours at concentrations as low as 0.5 micrograms per milliliter of tissue culture medium. Plicamycin has shown significant anti-tumor activity against experimental leukemia in mice when administered intraperitoneally. D06EPF DB06811 Polidocanol small molecule approved 9002-92-0 582.8073 C30H62O10 Polidocanol has a concentration and volume dependent damaging effect on the blood vessel endothelium. D05ZPL DB06813 Pralatrexate small molecule approved 146464-95-1 477.4726 C23H23N7O5 P04818#Thymidylate synthase@P00374#Dihydrofolate reductase D02LWU DB06814 Protokylol small molecule approved 136-70-9 331.368 C18H21NO5 P07550#Beta-2 adrenergic receptor Not Available DB06815 Pyrithione small molecule approved 1121-31-9 127.16 C5H5NOS Pyrithione zinc has a broad antimicrobial spectrum of activity, including fungi, gram-positive and gram-negative bacteria 2. Pyrithione zinc is effective against Malassezia and all other fungi, especially the Malassezia species found on scalp 5. In patients with dandruff, treatment with pyrithione zinc reduced the amount of fungus on the scalp, which reduces the amount of free fatty acids, thereby reducing scalp flaking and itch 5. DB06816 Pyrvinium small molecule approved 7187-62-4 382.53 C26H28N3 Pyrvinium is an anthelmintic agent which acts to kill pinworms 3. D0A0SP DB06817 Raltegravir small molecule approved 518048-05-0 444.4163 C20H21FN6O5 Q7ZJM1#Integrase Not Available D0I1FQ DB06819 Phenylbutyric acid small molecule approved 1821-12-1 164.2011 C10H12O2 P95468#Aromatic-amino-acid aminotransferase@P00800#Thermolysin Phenylbutyric acid decreases elevated plasma ammonia glutamine levels in patients with urea cycle disorders. It increases waste nitrogen excretion in the form of phenylacetylglutamine.2 DB06820 Sulconazole small molecule approved 61318-90-9 397.74 C18H15Cl3N2S The function of imidazole derivatives can be attributed to their structural resemblance to purines essential to metabolism. D0X8XA DB06821 Sulfameter small molecule approved 651-06-9 280.3 C11H12N4O3S P0AC13#Dihydropteroate synthase Not Available D07SYJ DB06823 Tiopronin small molecule approved 1953-02-2 163.19 C5H9NO3S Not Available D0A8CJ DB06824 Triethylenetetramine small molecule approved 112-24-3 146.2339 C6H18N4 Triethylenetetramine (TETA) is a selective copper(II) chelator that works to promote urinary copper excretion.8 It was shown to reduce excess body copper storage and ameliorate symptoms of Wilson’s disease. In rats with diabetes mellitus, intravenous administration of TETA led to a dose-dependent increase in urinary copper excretion.1 DB06825 Triptorelin small molecule approved 57773-63-4 1311.473 C64H82N18O13 P30968#Gonadotropin-releasing hormone receptor The first administration of triptorelin is followed by a transient surge of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol,and testosterone. The time, peak and decline of testosterone in the body varies depending on the dose administered. This initial surge is often responsible for worsening of prostate cancer symptoms such as urethral or bladder outlet obstruction, bone pain, spinal cord injury and hematuria in the early stages. A sustained decrease in FSH and LH, and significant reduction of testicular steroidogenesis is usually seen 2-4 weeks post-initiation of therapy. This result is a reduction of serum testosterone to levels which are typically seen in surgically castrated men. Ultimately, tissues and functions that require these hormones become inactive. The effects of triptorelin can usually be reversed once the drug is discontinued. D03QRS DB06826 Unoprostone small molecule approved 120373-36-6 382.541 C22H38O5 Unoprostone will begin to reduce IOP 30 minutes after ocular instillation. D09SRR DB06827 Viomycin small molecule approved 32988-50-4 685.69 C25H43N13O10 P9WJ63#16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA Not Available DB00615 Rifabutin small molecule approved 72559-06-9 847.0047 C46H62N4O11 P0A8V2#DNA-directed RNA polymerase subunit beta@P0A7Z4#DNA-directed RNA polymerase subunit alpha@P07900#Heat shock protein HSP 90-alpha@P14625#Endoplasmin@P0A8T7#DNA-directed RNA polymerase subunit beta' Rifabutin is an antibiotic that inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. It is bactericidal and has a very broad spectrum of activity against most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis. Because of rapid emergence of resistant bacteria, use is restricted to treatment of mycobacterial infections and a few other indications. Rifabutin is well absorbed when taken orally and is distributed widely in body tissues and fluids, including the CSF. It is metabolized in the liver and eliminated in bile and, to a much lesser extent, in urine, but dose adjustments are unnecessary with renal insufficiency. D05CHI DB00617 Paramethadione small molecule approved 115-67-3 157.1671 C7H11NO3 Q9P0X4#Voltage-dependent T-type calcium channel subunit alpha-1I Paramethadione is an oxazolidinedione anticonvulsant similar to trimethadione that acts on the central nervous system (CNS) to reduce the number of absence seizures (often seen in epileptics). Absence seizures involve an interruption to consciousness where the person experiencing the seizure seems to become vacant and unresponsive for a short period of time (usually up to 30 seconds). Paramethadione acts on thalamic neurons in the thalamic reticular nucleus (which studies have shown to be associated with absence seizures, von Krosigk et al., 1993). D09JBP DB00618 Demeclocycline small molecule approved 127-33-3 464.853 C21H21ClN2O8 P30518#Vasopressin V2 receptor Demeclocycline is a tetracycline antibiotic active against the following microorganisms: Rickettsiae (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, tick fevers), Mycoplasma pneumoniae (PPLO, Eaton agent), agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, the spirochetal agent of relapsing fever (Borrelia recurrentis), Haemophilus ducreyi (chancroid), Yersinia pestis, Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species, Vibrio comma and Vibrio fetus, and Brucella species (in conjunction with streptomycin). Demeclocycline inhibits cell growth by inhibiting translation. Demeclocycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane. Demeclocycline is not a direct bactericidal agent; rather, it is a bacteriostatic drug that impairs bacterial growth. Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time. D0R9WP DB00619 Imatinib small molecule approved 152459-95-5 493.6027 C29H31N7O P11274#Breakpoint cluster region protein@P10721#Mast/stem cell growth factor receptor Kit@O43519#RET proto-oncogene@P04629#High affinity nerve growth factor receptor@P07333#Macrophage colony-stimulating factor 1 receptor@P16234#Platelet-derived growth factor receptor alpha@Q08345#Epithelial discoidin domain-containing receptor 1@P00519#Tyrosine-protein kinase ABL1@P09619#Platelet-derived growth factor receptor beta@Q16832#Discoidin domain-containing receptor 2 Imatinib is a 2-phenylaminopyrimidine derivative neoplastic agent that belongs to the class of tyrosine kinase inhibitors.14 Although imatinib inhibits a number of tyrosine kinases, it is quite selective toward the BCR-ABL fusion protein that is present in various cancers.10 BCR-ABL pathway controls many downstream pathways that are heavily implicated in neoplastic growth such as the Ras/MapK pathway (cellular proliferation), Src/Pax/Fak/Rac pathway (cellular motility), and PI/PI3K/AKT/BCL-2 pathway (apoptosis pathway).7,8,9 Therefore, the BCR-ABL pathway is an attractive target for cancer treatment. Although normal cells also depend on these pathways for growth, these cells tend to have redundant tyrosine kinases to continually function in spite of ABL inhibition from imatinib.1 Cancer cells, on the other hand, can have a dependence on BCR-ABL, thus more heavily impacted by imatinib.1 D0AZ3C DB00620 Triamcinolone small molecule approved 124-94-7 394.4339 C21H27FO6 P04150#Glucocorticoid receptor Triamcinolone is a corticosteroid with anti-inflammatory properties.8 These properties are used to treat inflammation in conditions that affect various organs and tissues.15 Triamcinolone should not be administered as an epidural injection.10,12,13,15,16 D03BLF DB00621 Oxandrolone small molecule approved 53-39-4 306.4397 C19H30O3 P10275#Androgen receptor Oxandrolone is an anabolic steroids indicated as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections, or severe trauma, and in some patients who without definite pathophysiologic reasons fail to gain or to maintain normal weight, to offset the protein catabolism associated with prolonged administration of corticosteroids, and for the relief of the bone pain frequently accompanying osteoporosis. Anabolic steroids are synthetic derivatives of testosterone. D0U3GL DB00622 Nicardipine small molecule approved 55985-32-5 479.525 C26H29N3O6 P20309#Muscarinic acetylcholine receptor M3@P0DP23#Calmodulin@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@P08172#Muscarinic acetylcholine receptor M2@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q01064#Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B@P54750#Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A Nicardipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nicardipine is similar to other peripheral vasodilators. Nicardipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. D0T0KA DB00623 Fluphenazine small molecule approved 69-23-8 437.522 C22H26F3N3OS P0DP23#Calmodulin@P10275#Androgen receptor@P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C Fluphenazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Fluphenazine has not been shown effective in the management of behaviorial complications in patients with mental retardation. D0P5SA DB00624 Testosterone small molecule approved 58-22-0 288.4244 C19H28O2 P03372#Estrogen receptor@P10275#Androgen receptor@P08235#Mineralocorticoid receptor Testosterone antagonizes the androgen receptor to induce gene expression that causes the growth and development of masculine sex organs and secondary sexual characteristics.5,14,15,16,17,18,19,20 The duration of action of testosterone is variable from patient to patient with a half life of 10-100 minutes.14,15,16,17,18,19,20 The therapeutic index is wide considering the normal testosterone levels in an adult man range from 300-1000ng/dL.14,16,17,18,19,20 Counsel patients regarding the risk of secondary exposure of testosterone topical products to children.14,16,17,18,19 D06XMU DB00625 Efavirenz small molecule approved 154598-52-4 315.675 C14H9ClF3NO2 Q72547#Reverse transcriptase/RNaseH D07HVY DB00626 Bacitracin small molecule approved 1405-87-4 1422.693 C66H103N17O16S P14735#Insulin-degrading enzyme@P01023#Alpha-2-macroglobulin Bacitracin is a mixture of polypeptides that prevent the formation of the bacterial cell wall and oxidatively cleave DNA.1 It has a short duration of action as it must be given every 3 to 4 hours topically.10,11 Bacitracin is nephrotoxic when given intramuscularly and may lead to renal failure.4 D0M1IO DB00627 Niacin small molecule approved 59-67-6 123.1094 C6H5NO2 P49019#Hydroxycarboxylic acid receptor 3@Q8TDS4#Hydroxycarboxylic acid receptor 2@Q15274#Nicotinate-nucleotide pyrophosphorylase [carboxylating]@P40261#Nicotinamide N-methyltransferase Niacin is a B vitamin used to treat vitamin deficiencies as well as hyperlipidemia, dyslipidemia, hypertriglyceridemia, and to reduce the risk of myocardial infarctions.6,7,8,9,10,11 Niacin acts to decrease levels of very low density lipoproteins and low density lipoproteins, while increasing levels of high density lipoproteins.3 Niacin has a wide therapeutic window with usual oral doses between 500mg and 2000mg.6 Patients with diabetes, renal failure, uncontrolled hypothyroidism, and elderly patients taking niacin with simvastatin or lovastatin are at increased risk of myopathy and rhabdomyolysis.6 DB00628 Clorazepic acid small molecule approved 23887-31-2 314.723 C16H11ClN2O3 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Clorazepate is a member of the group of drugs called benzodiazepines. Pharmacologically, clorazepate has the characteristics of the benzodiazepines. It has depressant effects on the central nervous system. The primary metabolite, nordiazepam, quickly appears in the blood stream. Studies in healthy men have shown that clorazenate has depressant effects on the central nervous system. Since orally administered clorazepate dipotassium is rapidly decarboxylated to form nordiazepam, there is essentially no circulating parent drug. DB00629 Guanabenz small molecule approved 5051-62-7 231.082 C8H8Cl2N4 P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Guanabenz, a centrally acting α-2 adrenergic agonist, is indicated for treatment of hypertension. D0L4HY DB00630 Alendronic acid small molecule approved 66376-36-1 249.096 C4H13NO7P2 P14324#Farnesyl pyrophosphate synthase@P29074#Tyrosine-protein phosphatase non-receptor type 4@Q13332#Receptor-type tyrosine-protein phosphatase S@P23469#Receptor-type tyrosine-protein phosphatase epsilon@P38606#V-type proton ATPase catalytic subunit A Alendronic acid tablets have a very low oral bioavialabilityLabel2. After administration it distributes into soft tissue and bone or is excreted in the urineLabel. Alendronic acid does not undergo metabolismLabel. DB00631 Clofarabine small molecule approved 123318-82-1 303.677 C10H11ClFN5O3 P09884#DNA polymerase alpha catalytic subunit@P23921#Ribonucleoside-diphosphate reductase large subunit Clofarabine is a purine nucleoside antimetabolite that differs from other puring nucleoside analogs by the presence of a chlorine in the purine ring and a flourine in the ribose moiety. Clofarabine seems to interfere with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by clofarabine, other effects also occur. Clofarabine prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids, thus stopping the growth of cancer cells. D0R5RR DB00632 Docosanol small molecule approved 661-19-8 326.6 C22H46O P03200#Envelope glycoprotein GP350@P68344#Envelope glycoprotein GP340 Docosanol is a saturated 22-carbon aliphatic alcohol which exhibits antiviral activity against many lipid enveloped viruses including herpes simplex virus (HSV). Docosanol speeds the healing of cold sores and fever blisters on the face or lips. It also relieves the accompanying symptoms, including tingling, pain, burning, and itching. Docosanol cannot, however, prevent cold sores or fever blisters from appearing. D00AOJ DB00633 Dexmedetomidine small molecule approved 113775-47-6 200.2795 C13H16N2 P08913#Alpha-2A adrenergic receptor Dexmedetomidine activates 2-adrenoceptors, and causes the decrease of sympathetic tone, with attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery; it reduces anesthetic and opioid requirements; and causes sedation and analgesia. D0U3DU DB00634 Sulfacetamide small molecule approved 144-80-9 214.242 C8H10N2O3S P0C002#Dihydropteroate synthase type-1@P53848#Folic acid synthesis protein FOL1 Sulfacetamide is a sulfonamide antibiotic with bacteriostatic actions and broad-spectrum activity against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus. D0M4VM DB00635 Prednisone small molecule approved 53-03-2 358.4281 C21H26O5 P04150#Glucocorticoid receptor Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.1 Prednisone has a short duration of action as the half life is 2-3 hours.9 Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces.1 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.1 D0IL7L DB00636 Clofibrate small molecule approved 637-07-0 242.699 C12H15ClO3 Q07869#Peroxisome proliferator-activated receptor alpha Clofibrate is an antilipidemic agent similar to gemfibrozil. It acts to lower elevated serum lipids by reducing the very low-density lipoprotein fraction (Sf 20-400) rich in triglycerides. Serum cholesterol may be decreased, particularly in those patients whose cholesterol elevation is due to the presence of IDL as a result of Type III hyperlipoproteinemia. Several investigators have observed in their studies that clofibrate may produce a decrease in cholesterol linoleate but an increase in palmitoleate and oleate, the latter being considered atherogenic in experimental animals. The significance of this finding is unknown at this time. Reduction of triglycerides in some patients treated with clofibrate or certain of its chemically and clinically similar analogs may be associated with an increase in LDL cholesterol. Increase in LDL cholesterol has been observed in patients whose cholesterol is initially normal. Animal studies suggest that clofibrate interrupts cholesterol biosynthesis prior to mevalonate formation. D0J5DC DB00637 Astemizole small molecule approved 68844-77-9 458.5703 C28H31FN4O P70174#Histamine H1 receptor@Q12809#Potassium voltage-gated channel subfamily H member 2@O95259#Potassium voltage-gated channel subfamily H member 1@P10636#Microtubule-associated protein tau Astemizole is a second generation H1-receptor antagonist. It does not significantly cross the blood brain barrier and therefore does not cause drowsiness or CNS depression at normal doses. D0Y2HR DB00638 Inulin small molecule approved 9005-80-5 6179.3581 C228H382O191 Q9F0I5#Cycloinulo-oligosaccharide fructanotransferase The inulin test is a procedure by which the filtering capacity of the glomeruli (the main filtering structures of the kidney) is determined by measuring the rate at which inulin, the test substance, is cleared from blood plasma. Inulin is one of the more suitable and accurate substance to measure because it is a small, inert polysaccharide molecule that readily passes through the glomeruli. The inulin clearance test is performed by injecting inulin, waiting for it to be distributed, and then measuring plasma and urine inulin concentrations by various assays. As nutraceutical agents inulins may have antitumor, antimicrobial, hypolipidemic and hypoglycemic actions. They may also help to improve mineral absorption and balance and may have antiosteoporotic activity. D01IWS DB00639 Butoconazole small molecule approved 64872-76-0 411.776 C19H17Cl3N2S Butoconazole is an imidazole derivative that has fungicidal activity in vitro against Candida spp. and has been demonstrated to be clinically effective against vaginal infections due to Candida albicans. Candida albicans has been identified as the predominant species responsible for vulvovaginal candidasis. D0N3SP DB00640 Adenosine small molecule approved 58-61-7 267.2413 C10H13N5O4 P30542#Adenosine receptor A1@P29274#Adenosine receptor A2a@P29275#Adenosine receptor A2b@P0DMS8#Adenosine receptor A3 Adenosine is indicated as an adjunct to thallium-201 in myocardial perfusion scintigraphy and also indicated for conversion of sinus rhythm of paroxysmal supraventricular tachycardia.12,13 Adenosine has a short duration of action as the half life is <10 seconds, and a wide therapeutic window.12,13 Patients should be counselled regarding the risk of cardiovascular side effects, bronchoconstriction, seizures, and hypersensitivity.12,13 D06IAR DB00641 Simvastatin small molecule approved 79902-63-9 418.5662 C25H38O5 P04035#3-hydroxy-3-methylglutaryl-coenzyme A reductase@P20701#Integrin alpha-L@Q92769#Histone deacetylase 2 Simvastatin is an oral antilipemic agent which inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.3,4 D0H0ND DB00642 Pemetrexed small molecule approved 137281-23-3 427.4106 C20H21N5O6 P04818#Thymidylate synthase@P31939#Bifunctional purine biosynthesis protein PURH@P00378#Dihydrofolate reductase@P22102#Trifunctional purine biosynthetic protein adenosine-3 Preclinical studies have shown that pemetrexed inhibits the in vitro growth of mesothelioma cell lines (MSTO-211H, NCI-H2052). Studies with the MSTO-211H mesothelioma cell line showed synergistic effects when pemetrexed was combined concurrently with cisplatin. D0Y4GO DB00643 Mebendazole small molecule approved 31431-39-7 295.2927 C16H13N3O3 Q71U36#Tubulin alpha-1A chain@P68371#Tubulin beta-4B chain Mebendazole is a (synthetic) broad-spectrum anthelmintic. The principal mode of action for Mebendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules. D0J1MI DB00644 Gonadorelin small molecule approved 33515-09-2 1182.2901 C55H75N17O13 P30968#Gonadotropin-releasing hormone receptor@Q96P88#Putative gonadotropin-releasing hormone II receptor Gonadorelin is responsible for the release of follicle stimulating hormone and leutinizing hormone from the anterior pitutitary. In the pituitary GnRH stimulates synthesis and release of FSH and LH, a process that is controlled by the frequency and amplitude of GnRH pulses, as well as the feedback of androgens and estrogens. The pulsatility of GnRH secretion has been seen in all vertebrates, and it is necessary to ensure a correct reproductive function. Thus a single hormone, GnRH, controls a complex process of follicular growth, ovulation, and corpus luteum maintenance in the female, and spermatogenesis in the male. Its short half life requires infusion pumps for its clinical use D04ODH DB00645 Dyclonine small molecule approved 586-60-7 289.4125 C18H27NO2 Q9Y5Y9#Sodium channel protein type 10 subunit alpha Dyclonine is an oral anasthetic. If substantial quantities of local anesthetics are absorbed through the mucosa, actions on the central nervous system (CNS) may cause CNS stimulation and/or CNS depression. Actions on the cardiovascular system may cause depression of cardiac conduction and excitability and, with some of these agents, peripheral vasodilation. D04QLR DB00646 Nystatin small molecule approved 1400-61-9 926.107 C47H75NO17 Nystatin is an antifungal that is both fungistatic and fungicidal in vitro against a wide variety of yeasts and yeast-like fungi. It exerts its antifungal effects via disruption of the fungal cell membrane. Resistance to nystatin is minimal in Candida albicans, but tends to develop in other species of Candida.8 Nystatin carries no significant activity against bacteria, protozoa, or viruses. It carries significant systemic toxicity and is currently unavailable in a formula appropriate for systemic use - its efficacy is currently restricted, therefore, to topical, oral, and gastrointestinal infections.2 D08XAC DB00647 Dextropropoxyphene small molecule approved 469-62-5 339.4712 C22H29NO2 P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor@P23141#Liver carboxylesterase 1 Propoxyphene, a synthetic opiate agonist, is structurally similar to methadone. Its general pharmacologic properties are those of the opiates as a group. The analgesic effect of propoxyphene is due to the d-isomer, dextropropoxyphene. It binds to the opiate receptors and leads to a decrease of the perception of pain stimuli. Propoxyphene possesses little to no antitussive activity and no antipyretic action. D0D4PB DB00648 Mitotane small molecule approved 53-19-0 320.041 C14H10Cl4 P15538#Cytochrome P450 11B1, mitochondrial@P06401#Progesterone receptor@P10275#Androgen receptor@P10109#Adrenodoxin, mitochondrial Mitotane is an oral chemotherapeutic agent indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. Mitotane can best be described as an adrenal cytotoxic agent, although it can cause adrenal inhibition, apparently without cellular destruction. The administration of Mitotane alters the extra-adrenal metabolism of cortisol in man; leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall. The drug apparently causes increased formation of 6-B-hydroxyl cortisol. D0Z5OE DB00649 Stavudine small molecule approved 3056-17-5 224.2133 C10H12N2O4 Q72547#Reverse transcriptase/RNaseH Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Stavudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. D0Z8EX DB00650 Leucovorin small molecule approved 58-05-9 473.446 C20H23N7O7 Leucovorin is one of several active, chemically reduced derivatives of folic acid. It is useful as an antidote to drugs which act as folic acid antagonists. Leucovorin is a mixture of the diastereoisomers of the 5-formyl derivative of tetrahydrofolic acid (THF). The biologically active compound of the mixture is the (-)-l-isomer, known as Citrovorum factor or (-)-folinic acid. Leucovorin does not require reduction by the enzyme dihydrofolate reductase in order to participate in reactions utilizing folates as a source of “one-carbon” moieties. Administration of leucovorin can counteract the therapeutic and toxic effects of folic acid antagonists such as methotrexate, which act by inhibiting dihydrofolate reductase. Leucovorin has also been used to enhance the activity of fluorouracil. DB00651 Dyphylline small molecule approved 479-18-5 254.2426 C10H14N4O4 Q07343#cAMP-specific 3',5'-cyclic phosphodiesterase 4B@P27815#cAMP-specific 3',5'-cyclic phosphodiesterase 4A@Q08493#cAMP-specific 3',5'-cyclic phosphodiesterase 4C@Q08499#cAMP-specific 3',5'-cyclic phosphodiesterase 4D@P30542#Adenosine receptor A1@P29274#Adenosine receptor A2a Dyphylline, a xanthine derivative, is a bronchodilator used for relief of acute bronchial asthma and for reversible bronchospasm associated with chronic bronchitis and emphysema. Dyphylline is a xanthine derivative with pharmacologic actions similar to theophylline and other members of this class of drugs. Its primary action is that of bronchodilation, but it also exhibits peripheral vasodilatory and other smooth muscle relaxant activity to a lesser degree. D02PWM DB00652 Pentazocine small molecule approved 359-83-1 285.4238 C19H27NO Q99720#Sigma non-opioid intracellular receptor 1@P35372#Mu-type opioid receptor@P41145#Kappa-type opioid receptor Pentazocine is a potent analgesic which when administered orally in a 50 mg dose appears equivalent in analgesic effect to 60 mg (1 grain) of codeine. Onset of significant analgesia usually occurs between 15 and 30 minutes after oral administration, and duration of action is usually three hours or longer. Onset and duration of action and the degree of pain relief are related both to dose and the severity of pretreatment pain. Pentazocine weakly antagonizes the analgesic effects of morphine and meperidine; in addition, it produces incomplete reversal of cardiovascular, respiratory, and behavioral depression induced by morphine and meperidine. Pentazocine has about 1/50 the antagonistic activity of nalorphine. It also has sedative activity. D0W6DG DB00653 Magnesium sulfate small molecule approved 7487-88-9 120.368 MgO4S Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A Magnesium sulfate is a small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. Magnesium sulfate is gaining popularity as an initial treatment in the management of various dysrhythmias, particularly torsades de pointes, and dyrhythmias secondary to TCA overdose or digitalis toxicity. DB00654 Latanoprost small molecule approved 130209-82-4 432.5928 C26H40O5 P43088#Prostaglandin F2-alpha receptor Latanoprost effectively decreases intraocular pressure by increasing uveoscleral outflow.2 A decrease in intraocular pressure has been measured within 3–4 hours post-administration, reaches a maximum decrease at 8–12 hours, and can be maintained for a period of 24 hours.3 D0C6NM DB00655 Estrone small molecule approved 53-16-7 270.3661 C18H22O2 P03372#Estrogen receptor@P10275#Androgen receptor@P04278#Sex hormone-binding globulin@Q92731#Estrogen receptor beta@P11511#Aromatase Estrone, a synthetically prepared or naturally occurring steroidal estrogen obtained from pregnant equine urine, is the primary circulating estrogen after menopause. Estrone is naturally derived from the peripheral conversion of androstenedione by an aromatase enzyme found in adipose tissues and is converted to estradiol in peripheral tissues. The estrogenic potency of estrone is one third that of estradiol. Estropipate is piperazine-stabilized estrone sulfate. Estrone, and estropipate are used to treat abnormalities related to gonadotropin hormone dysfunction, vasomotor symptoms, atrophic vaginitis, and vulvar atrophy associated with menopause, and for the prevention of osteoporosis due to estrogen deficiency. D00ZFP DB00656 Trazodone small molecule approved 19794-93-5 371.864 C19H22ClN5O P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P31645#Sodium-dependent serotonin transporter@P08908#5-hydroxytryptamine receptor 1A@P70174#Histamine H1 receptor@P35348#Alpha-1A adrenergic receptor@P08913#Alpha-2A adrenergic receptor Trazodone treats depressed mood and other depression-related symptoms and shows benefit in the treatment of insomnia due to its sedating effects.20 It is known to prolong the cardiac QT-interval.21 Memory, alertness, and cognition may be decreased by trazodone, especially in elderly patients due to its central nervous system depressant effects.9 D00USF DB00657 Mecamylamine small molecule approved 60-40-2 167.2911 C11H21N Q15822#Neuronal acetylcholine receptor subunit alpha-2@P36544#Neuronal acetylcholine receptor subunit alpha-7@P43681#Neuronal acetylcholine receptor subunit alpha-4@P17787#Neuronal acetylcholine receptor subunit beta-2 Mecamylamine is a potent, oral antihypertensive agent and ganglion blocker, and is a secondary amine. Mecamylamine is indicated for the management of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension. Mecamylamine reduces blood pressure in both normotensive and hypertensive individuals. A small oral dosage often produces a smooth and predictable reduction of blood pressure. Although this antihypertensive effect is predominantly orthostatic, the supine blood pressure is also significantly reduced. Mecamylamine crosses the blood-brain and placental barriers. D0V8HA DB00658 Sevelamer small molecule approved 52757-95-6 149.619 C6H12ClNO Patients with end-stage renal disease (ESRD) retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum calcium resulting in ectopic calcification. When the product of serum calcium and phosphorus concentrations (Ca x P) exceeds 55 mg2/dL2, there is an increased risk that ectopic calcification will occur. Hyperphosphatemia plays a role in the development of secondary hyperparathyroidism in renal insufficiency. An increase in parathyroid hormone (PTH) levels is characteristic of patients with chronic renal failure. Increased levels of PTH can lead to osteitis fibrosa, a bone disease. A decrease in serum phosphorus may decrease serum PTH levels. Treatment of hyperphosphatemia includes reduction in dietary intake of phosphate, inhibition of intestinal phosphate absorption with phosphate binders, and removal of phosphate with dialysis. Sevelamer taken with meals has been shown to decrease serum phosphorus concentrations in patients with ESRD who are on hemodialysis. In vitro studies have shown that the capsule and tablet formulations bind phosphate to a similar extent. Sevelamer treatment also results in a lowering of low-density lipoprotein (LDL) and total serum cholesterol levels. DB00659 Acamprosate small molecule approved 77337-76-9 181.21 C5H11NO4S Q9UBS5#Gamma-aminobutyric acid type B receptor subunit 1@P41594#Metabotropic glutamate receptor 5@Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B Acamprosate acts on the CNS, aiding in the restoration of normal glutaminergic neuron activity.1 Pharmacodynamic studies have shown that acamprosate calcium reduces alcohol intake in alcohol-dependent individuals, likely through effects on NMDA receptors and calcium channels.7 It is a safe and well-tolerated drug for patients with alcohol dependency and improves the likelihood of alcohol abstinence.1,12 D0GC2M DB00660 Metaxalone small molecule approved 1665-48-1 221.2524 C12H15NO3 D0S5CH DB00661 Verapamil small molecule approved 52-53-9 454.6016 C27H38N2O4 Q12809#Potassium voltage-gated channel subfamily H member 2@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q00975#Voltage-dependent N-type calcium channel subunit alpha-1B Verapamil is an L-type calcium channel blocker with antiarrhythmic, antianginal, and antihypertensive activity.19 Immediate-release verapamil has a relatively short duration of action, requiring dosing 3 to 4 times daily,19 but extended-release formulations are available that allow for once-daily dosing.17,22 As verapamil is a negative inotropic medication (i.e. it decreases the strength of myocardial contraction), it should not be used in patients with severe left ventricular dysfunction or hypertrophic cardiomyopathy as the decrease in contractility caused by verapamil may increase the risk of exacerbating these pre-existing conditions.17 D0R0FE DB00662 Trimethobenzamide small molecule approved 138-56-7 388.4574 C21H28N2O5 Trimethobenzamide is a novel antiemetic which prevents nausea and vomiting in humans. Its actions are unclear but most likely involves the chemoreceptor trigger zone (CTZ). In dogs pretreated with trimethobenzamide HCl, the emetic response to apomorphine is inhibited, while little or no protection is afforded against emesis induced by intragastric copper sulfate. D0A8FB DB00663 Flumethasone small molecule approved 2135-17-3 410.458 C22H28F2O5 P04150#Glucocorticoid receptor Flumethasone pivalate is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. As it is a privalate salt, its anti-inflammatory action is concentrated at the site of application. This local effect on diseased areas results in a prompt decrease in inflammation, exudation and itching. DB00664 Sulfametopyrazine small molecule approved 152-47-6 280.303 C11H12N4O3S Q27738#Dihydropteroate synthetase Sulfametopyrazine is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus. D0F0OK DB00665 Nilutamide small molecule approved 63612-50-0 317.2207 C12H10F3N3O4 P10275#Androgen receptor Nilutamide is an antineoplastic hormonal agent primarily used in the treatment of prostate cancer. Nilutamide is a pure, nonsteroidal anti-androgen with affinity for androgen receptors (but not for progestogen, estrogen, or glucocorticoid receptors). Consequently, Nilutamide blocks the action of androgens of adrenal and testicular origin that stimulate the growth of normal and malignant prostatic tissue. Prostate cancer is mostly androgen-dependent and can be treated with surgical or chemical castration. To date, antiandrogen monotherapy has not consistently been shown to be equivalent to castration. The relative binding affinity of nilutamide at the androgen receptor is less than that of bicalutamide, but similar to that of hydroxuflutamide. D0SN9T DB00666 Nafarelin small molecule approved 76932-56-4 1322.496 C66H83N17O13 P30968#Gonadotropin-releasing hormone receptor@Q96P88#Putative gonadotropin-releasing hormone II receptor Nafarelin is a potent agonistic analog of gonadotropin-releasing hormone (GnRH). At the onset of administration, nafarelin stimulates the release of the pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), resulting in a temporary increase of gonadal steroidogenesis. Repeated dosing abolishes the stimulatory effect on the pituitary gland. Twice daily administration leads to decreased secretion of gonadal steroids by about 4 weeks; consequently, tissues and functions that depend on gonadal steroids for their maintenance become quiescent. After nafarelin therapy is discontinued, pituitary and ovarian function normalize and estradiol serum concentrations increase to pretreatment levels. Recurrences of endometriosis are frequent after cessation of any hormonal therapy, or surgery that leaves the ovaries and/or uterus intact. D08WYM DB00668 Epinephrine small molecule approved 51-43-4 183.2044 C9H13NO3 P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P25100#Alpha-1D adrenergic receptor@P01375#Tumor necrosis factor Epinephrine is a sympathomimetic drug. It causes an adrenergic receptive mechanism on effector cells and mimics all actions of the sympathetic nervous system except those on the facial arteries and sweat glands 18. D04PHC DB00669 Sumatriptan small molecule approved 103628-46-2 295.4 C14H21N3O2S P08908#5-hydroxytryptamine receptor 1A@P28221#5-hydroxytryptamine receptor 1D@P28222#5-hydroxytryptamine receptor 1B@P30939#5-hydroxytryptamine receptor 1F Sumatriptan constricts cranial blood vessels and prevents the release of vasoactive peptides.2 The dose of sumatriptan varies widely by route of administration and in most cases, no more than 2 doses should be given daily.5,6,7,8,9,10 Medication overuse headaches may occur in patients who use sumatriptan frequently.5,6,7,8,9,10 D0Z6UC DB00670 Pirenzepine small molecule approved 28797-61-7 351.4023 C19H21N5O2 P11229#Muscarinic acetylcholine receptor M1 Pirenzepine belongs to a group of medications called antispasmodics/anticholinergics. These medications are used to relieve cramps or spasms of the stomach, intestines, and bladder. Pirenzepine is used to treat duodenal or stomach ulcers or intestine problems. It can be used together with antacids or other medicine in the treatment of peptic ulcer. It may also be used to prevent nausea, vomiting, and motion sickness. D0T0LM DB00671 Cefixime small molecule approved 79350-37-1 453.45 C16H15N5O7S2 Cefixime, an antibiotic, is a third-generation cephalosporin like ceftriaxone and cefotaxime. Cefixime is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. The antibacterial effect of cefixime results from inhibition of mucopeptide synthesis in the bacterial cell wall. D06OVY DB00672 Chlorpropamide small molecule approved 94-20-2 276.74 C10H13ClN2O3S Q09428#ATP-binding cassette sub-family C member 8 Chlorpropamide, a second-generation sulfonylurea antidiabetic agent, is used with diet to lower blood glucose levels in patients with diabetes mellitus type II. Chlorpropamide is twice as potent as the related second-generation agent glipizide. D00BCP DB00673 Aprepitant small molecule approved 170729-80-3 534.4267 C23H21F7N4O3 P25103#Substance-P receptor Aprepitant, an antiemetic, is a substance P/neurokinin 1 (NK1) receptor antagonist which, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CI NV). D0GU4K DB00674 Galantamine small molecule approved 357-70-0 287.3535 C17H21NO3 P22303#Acetylcholinesterase@P36544#Neuronal acetylcholine receptor subunit alpha-7@A9X444#Muscle nicotinic acetylcholine receptor@P06276#Cholinesterase Galantamine is a competitive and reversible inhibitor of acetylcholinesterase that works to increase acetylcholine levels.10 Galantamine acts both centrally and peripherally to inhibit both muscle and brain acetylcholinesterase, thereby increasing cholinergic tone.5 Galantamine is also a positive allosteric modulator of neuronal nicotinic acetylcholine receptors.3,5 As dementia is a progressive neurodegenerative disease, galatamine has a negligible effect in altering the course of the underlying process of dementia 10 and may exert its therapeutic effectiveness for a short period of time.8 However, galantamine promoted improvements in cognition, global function, activities of daily living, and behavioural symptoms in clinical studies of Alzheimer’s disease.1,7 D0R9VR DB00675 Tamoxifen small molecule approved 10540-29-1 371.5146 C26H29NO P03372#Estrogen receptor@P04278#Sex hormone-binding globulin@Q92731#Estrogen receptor beta@P17252#Protein kinase C alpha type@P05771#Protein kinase C beta type@Q05655#Protein kinase C delta type@Q02156#Protein kinase C epsilon type@P05129#Protein kinase C gamma type@P41743#Protein kinase C iota type@Q04759#Protein kinase C theta type Tamoxifen is a selective estrogen receptor modulator that inhibits growth and promotes apoptosis in estrogen receptor positive tumors.1,8 It has a long duration of action as the active metabolite N-desmethyltamoxifen has a half life of approximately 2 weeks.15,16 It has a narrow therapeutic index as higher doses can lead to breathing difficulty or convulsions.15,16 Tamoxifen administration is also associated with an increased incidence of uterine malignancies.15,16 D07KSG DB00676 Benzyl benzoate small molecule approved 120-51-4 212.2439 C14H12O2 Benzyl benzoate is one of the older preparations used to treat scabies. Scabies is a skin infection caused by the mite sarcoptes scabiei. It is characterised by severe itching (particularly at night), red spots, and may lead to a secondary infection. Benzyl benzoate is lethal to this mite and so is useful in the treatment of scabies. It is also used to treat lice infestation of the head and body. Benzyl benzoate is not the treatment of choice for scabies due to its irritant properties. DB00677 Isoflurophate small molecule approved 55-91-4 184.1457 C6H14FO3P P22303#Acetylcholinesterase@P06276#Cholinesterase@P02787#Serotransferrin Isoflurophate is used as ocular drops in the treatment of chronic glaucoma. Isoflurophate is an organophosphorus compound that acts as an irreversible cholinesterase inhibitor. As such, it displays parasympathomimetic effects. Isoflurophate is used in the eye to treat certain types of glaucoma and other eye conditions, such as accommodative esotropia. They may also be used in the diagnosis of certain eye conditions, such as accommodative esotropia. Isoflurophate damages the acetylcholinesterase enzyme and is therefore irreversible, however, pralidoxime can displace organophosphates such as isoflurophate from acetylcholinesterase, but only if administered before isoflurophate damages (alkylates) the enzyme. D0B2OT DB00678 Losartan small molecule approved 114798-26-4 422.911 C22H23ClN6O P30556#Type-1 angiotensin II receptor Losartan is an angiotensin II receptor blocker used to treat hypertension, diabetic nephropathy, and to reduce the risk of stroke.1,3,4 Losartan has a long duration of action as it is given once daily.3,4 Patients taking losartan should be regularly monitored for hypotension, renal function, and potassium levels.3,4 D0DD0K DB00679 Thioridazine small molecule approved 50-52-2 370.575 C21H26N2S2 P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P28223#5-hydroxytryptamine receptor 2A@Q12809#Potassium voltage-gated channel subfamily H member 2 Thioridazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Thioridazine has not been shown effective in the management of behaviorial complications in patients with mental retardation. D0U1OE DB00680 Moricizine small molecule approved 31883-05-3 427.517 C22H25N3O4S Q14524#Sodium channel protein type 5 subunit alpha Moricizine is used to treat irregular heartbeats (arrhythmias) and to maintain a normal heart rate. It acts on the heart muscle to improve the heart's rhythm. Moricizine has potent local anesthetic activity and membrane stabilizing effect. Decreases excitability, conduction velocity, and automaticity as a result of slowed atrioventricular (AV) nodal and His-Purkinje conduction. Decreases the action potential duration (APD) in Purkinje fibers; also decreases the effective refractory period (ERP) but to a lesser extent than the APD, so the ERP/APD ratio is increased. Decreases the maxiumum rate of Phase 0 depolarization (V max ), but does not affect action potential amplitude or maximum diastolic potential. Does not affect atrial, AV nodal, or left ventricular refractory periods and has minimal effect on ventricular repolarization (evidenced by the overall decrease in JT interval). Has no effect on sinoatrial (SA) nodal or intra-atrial conduction and only minimal effect on sinus cycle length and sinus node recovery time. In the Vaughan Williams classification of antiarrhythmics, moricizine is considered to be a class I agent. It has properties of class IA, IB, and IC agents but does not clearly belong to any of the three subclasses. It has less effect on the slope of phase 0 and a greater effect on action potential duration and effective refractory period than class IC agents. D04VPA DB00681 Amphotericin B small molecule approved 1397-89-3 924.079 C47H73NO17 Amphotericin B shows a high order of in vitro activity against many species of fungi. Histoplasma capsulatum, Coccidioides immitis, Candida species, Blastomyces dermatitidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenckii, Mucor mucedo, and Aspergillus fumigatus are all inhibited by concentrations of amphotericin B ranging from 0.03 to 1.0 mcg/mL in vitro. While Candida albicans is generally quite susceptible to amphotericin B, non-albicans species may be less susceptible. Pseudallescheria boydii and Fusarium sp. are often resistant to amphotericin B. The antibiotic is without effect on bacteria, rickettsiae, and viruses. D02DWM DB00682 Warfarin small molecule approved 81-81-2 308.3279 C19H16O4 Q9BQB6#Vitamin K epoxide reductase complex subunit 1@O75469#Nuclear receptor subfamily 1 group I member 2 Warfarin is an anticoagulant, as such it disrupts the coagulation cascade to reduce frequency and extent of thrombus formation.Label,17 In patients with deep vein thrombosis or atrial fibrillation there is an increased risk of thrombus formation due to the reduced movement of blood.15 For patients with cardiac valve disease or valve replacements this increased coagulability is due to tissue damage. Thrombi due to venous thrombosis can travel to the lungs and become pulmonary emboli, blocking circulation to a portion of lung tissue. Thrombi which form in the heart can travel to the brain and cause ischemic strokes. Prevention of these events is the primary goal of warfarin therapy. D0E3OF DB00683 Midazolam small molecule approved 59467-70-8 325.767 C18H13ClFN3 P28472#Gamma-aminobutyric acid receptor subunit beta-3 General effects D0U6LM DB00684 Tobramycin small molecule approved 32986-56-4 467.5145 C18H37N5O9 Tobramycin is an aminoglycoside antibiotic derived from the actinomycete Streptomyces tenebrarius.15 It has a broad spectrum of activity against Gram-negative bacteria, including Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Moraxella lacunata, Proteus spp., Haemophilus spp., Acinetobacter spp., Neisseria spp., and, importantly, Pseudomonas aeruginosa. Aminoglycosides also generally retain activity against the biothreat agents Yersinia pestis and Francisella tularensis. In addition, aminoglycosides are active against some Gram-positive bacteria such as Staphylococcus spp., including methicillin-resistant (MRSA) and vancomycin-resistant strains, Streptococcus spp., and Mycobacterium spp.1,14 D07BCT DB00685 Trovafloxacin small molecule approved 147059-72-1 416.36 C20H15F3N4O3 P11388#DNA topoisomerase 2-alpha Trovafloxacin is a broad spectrum antibiotic that inhibits DNA supercoiling in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It is not used widely due to the risk of hepatotoxicity. It tends to have better gram-positive bacterial coverage and less gram-negative coverage than the previous fluoroquinolones. Mechanism of action of fluoroquinolones including trovafloxacin is different from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines. Therefore fluoroquinolones may be active against pathogens that are resistant to these antibiotics. There is no cross-resistance between trovafloxacin and the mentioned classes of antibiotics. The overall results obtained from in vitro synergy studies, testing combinations of trovafloxacin with beta-lactams and aminoglycosides, indicate that synergy is strain specific and not commonly encountered. This agrees with results obtained previously with other fluoroquinolones. Resistance to trovafloxacin in vitro develops slowly via multiple-step mutation in a manner similar to other fluoroquinolones. Resistance to trovafloxacin in vitro occurs at a general frequency of between 1x10-7 to 10-10. Although cross-resistance has been observed between trovafloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to trovafloxacin. D03WPA DB00686 Pentosan polysulfate small molecule approved 37300-21-3 602.497 C10H18O21S4 P09038#Fibroblast growth factor 2@P05230#Fibroblast growth factor 1@P08620#Fibroblast growth factor 4 Pentosan polysulfate sodium is a low molecular weight heparin-like compound. It has anticoagulant and fibrinolytic effects. DB00687 Fludrocortisone small molecule approved 127-31-1 380.4504 C21H29FO5 P08235#Mineralocorticoid receptor@P04150#Glucocorticoid receptor Fludrocortisone is a synthetic mineralocorticoid used to replace endogenous aldosterone in conditions resulting in missing or inadequate endogenous synthesis.14,15 It acts on the kidneys to increase both sodium reabsorption and potassium excretion.13,11 As its effects are exerted at the transcriptional level, a single dose of fludrocortisone may work over the course of 1-2 days15 despite a relatively short plasma half-life.6,9,10 Like other systemic corticosteroids, fludrocortisone may mask signs of infection by depressing the normal immune response - infections occurring during fludrocortisone therapy should be promptly treated with appropriate antimicrobial therapy.14 D0R7JT DB00688 Mycophenolate mofetil small molecule approved 128794-94-5 433.4947 C23H31NO7 P20839#Inosine-5'-monophosphate dehydrogenase 1@P12268#Inosine-5'-monophosphate dehydrogenase 2@Q03393#6-pyruvoyl tetrahydrobiopterin synthase Mycophenolate mofetil is a prodrug of mycophenolic acid (MPA). The active form of mycophenolate, MPA, prevents the proliferation of immune cells and the formation of antibodies that cause transplant rejection.3 The above effects lead to higher rates of successful transplantation, avoiding the devastating effects of graft rejection. D04FBR DB00689 Cephaloglycin small molecule approved 3577-01-3 405.425 C18H19N3O6S P02919#Penicillin-binding protein 1B Cephaloglycin is an antibiotic related to cephalosporin but no longer in common use. It is an orally absorbed derivative of cephalosporin C. D07WZH DB00690 Flurazepam small molecule approved 17617-23-1 387.878 C21H23ClFN3O P28472#Gamma-aminobutyric acid receptor subunit beta-3 Flurazepam, a benzodiazepine derivative, is a hypnotic agent which does not appear to decrease dream time as measured by rapid eye movements (REM). Furthermore, it decreases sleep latency and number of awakenings for a consequent increase in total sleep time. D08XFV DB00691 Moexipril small molecule approved 103775-10-6 498.5681 C27H34N2O7 P12821#Angiotensin-converting enzyme Moexipril is a non-sulfhydryl containing precursor of the active angiotensin-converting enzyme (ACE) inhibitor moexiprilat. It is used to treat high blood pressure (hypertension). It works by relaxing blood vessels, causing them to widen. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems. D00HDU DB00692 Phentolamine small molecule approved 50-60-2 281.3523 C17H19N3O P35348#Alpha-1A adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor Phentolamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phentolamine is a long-acting, adrenergic, alpha-receptor blocking agent which can produce and maintain "chemical sympathectomy" by oral administration. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. Phentolamine works by blocking alpha receptors in certain parts of the body. Alpha receptors are present in the muscle that lines the walls of blood vessels. When the receptors are blocked by Phentolamine, the muscle relaxes and the blood vessels widen. This widening of the blood vessels results in a lowering of blood pressure. D01JUF DB00693 Fluorescein small molecule approved 2321-07-5 332.3063 C20H12O5 P06310#Ig kappa chain V-II region RPMI 6410 Not Available DB00694 Daunorubicin small molecule approved 20830-81-3 527.5199 C27H29NO10 P11388#DNA topoisomerase 2-alpha@Q02880#DNA topoisomerase 2-beta Daunorubicin is an anthracycline antibiotic and antineoplastic agent.5 It acts by inhibiting cellular reproduction through interference with DNA replication although it may contribute to the induction of cell death by increasing oxidative stress through the generation of reactive oxygen species and free radicals. As an antineoplastic agent, daunorubicin carries significant toxicities including cytopenias, hepatotoxicity, and extravasation reactions. Like other anthracyclines, daunorubicin also exhibits cardiotoxicity in proportion with the cumulative dose received over time. D01XWG DB00695 Furosemide small molecule approved 54-31-9 330.744 C12H11ClN2O5S Q13621#Solute carrier family 12 member 1@P00918#Carbonic anhydrase 2@Q9HC97#G-protein coupled receptor 35 Furosemide manages hypertension and edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome. Furosemide is a potent loop diuretic that works to increase the excretion of Na+ and water by the kidneys by inhibiting their reabsorption from the proximal and distal tubules, as well as the loop of Henle.9 It works directly acts on the cells of the nephron and indirectly modifies the content of the renal filtrate.8 Ultimately, furosemide increases the urine output by the kidney. Protein-bound furosemide is delivered to its site of action in the kidneys and secreted via active secretion by nonspecific organic transporters expressed at the luminal site of action.4,9 D0PQ3G DB00696 Ergotamine small molecule approved 113-15-5 581.6615 C33H35N5O5 P08913#Alpha-2A adrenergic receptor@P41595#5-hydroxytryptamine receptor 2B@P14416#D(2) dopamine receptor@P28222#5-hydroxytryptamine receptor 1B@P21728#D(1A) dopamine receptor Ergotamine is a vasoconstrictor and alpha adrenoreceptor antagonist. The pharmacological properties of ergotamine are extremely complex; some of its actions are unrelated to each other, and even mutually antagonistic. The drug has partial agonist and/or antagonist activity against tryptaminergic, dopaminergic and alpha adrenergic receptors depending upon their site, and it is a highly active uterine stimulant. It causes constriction of peripheral and cranial blood vessels and produces depression of central vasomotor centers. The pain of a migraine attack is believed to be due to greatly increased amplitude of pulsations in the cranial arteries, especially the meningeal branches of the external carotid artery. Ergotamine reduces extracranial blood flow, causes a decline in the amplitude of pulsation in the cranial arteries, and decreases hyperperfusion of the territory of the basilar artery. It does not reduce cerebral hemispheric blood flow. D01TSI DB00697 Tizanidine small molecule approved 51322-75-9 253.711 C9H8ClN5S Q9Y2I1#Nischarin@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor A note on spasticity D01MDT DB00698 Nitrofurantoin small molecule approved 67-20-9 238.159 C8H6N4O5 P0A7R5#30S ribosomal protein S10@P17117#Oxygen-insensitive NADPH nitroreductase Nitrofurantoin interferes with vital processes in bacteria, which leads to their death.2 Nitrofurantoin rapidly reaches therapeutic concentrations in the urine and is also cleared rapidly.3 D0R0BX DB00699 Nicergoline small molecule approved 27848-84-6 484.386 C24H26BrN3O3 P35348#Alpha-1A adrenergic receptor Nicergoline is a potent vasodilator (improves brain blood flow). On the cerebral level it prompts a lowering of vascular resistance, an increase in arterial flow and stimulates the use of oxygen and glucose. Nicergoline also improves blood circulation in the lungs and limbs and has been shown to inhibit blood platelet aggregation. D0V2GH DB00700 Eplerenone small molecule approved 107724-20-9 414.4914 C24H30O6 P08235#Mineralocorticoid receptor Eplerenone, an aldosterone receptor antagonist similar to spironolactone, has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulating levels do not overcome the effects of eplerenone. Eplerenone selectively binds to recombinant human mineralocorticoid receptors relative to its binding to recombinant human glucocorticoid, progesterone and androgen receptors. D0Q4SD DB00701 Amprenavir small molecule approved 161814-49-9 505.627 C25H35N3O6S Amprenavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Amprenavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. D0A0OO DB00703 Methazolamide small molecule approved 554-57-4 236.26 C5H8N4O3S2 P00915#Carbonic anhydrase 1@P22748#Carbonic anhydrase 4@P00918#Carbonic anhydrase 2@P43166#Carbonic anhydrase 7@P07451#Carbonic anhydrase 3 Methazolamide is topical carbonic anhydrase inhibitor. Methazolamide is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to beta-blockers. Methazolamide is a sulfonamide derivative; however, it does not have any clinically significant antimicrobial properties. Although methazolamide achieves a high concentration in the cerebrospinal fluid, it is not-considered an effective anticonvulsant. Methazolamide has a weak and transient diuretic effect, therefore use results in an increase in urinary volume, with excretion of sodium, potassium and chloride. D0C2II DB00704 Naltrexone small molecule approved 16590-41-3 341.4009 C20H23NO4 P35372#Mu-type opioid receptor@P41145#Kappa-type opioid receptor@P41143#Delta-type opioid receptor@Q99720#Sigma non-opioid intracellular receptor 1 Naltrexone, a pure opioid antagonist, is a synthetic congener of oxymorphone with no opioid agonist properties. Naltrexone is indicated in the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. It markedly attenuates or completely blocks, reversibly, the subjective effects of intravenously administered opioids. When co-administered with morphine, on a chronic basis, naltrexone blocks the physical dependence to morphine, heroin and other opioids. In subjects physically dependent on opioids, naltrexone will precipitate withdrawal symptomatology. D0PG8O DB00705 Delavirdine small molecule approved 136817-59-9 456.561 C22H28N6O3S Q72547#Reverse transcriptase/RNaseH Delavirdine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Delavirdine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of Delavirdine does not compete with template or nucleoside triphosphates. HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by Delavirdine. D0G6SD DB00706 Tamsulosin small molecule approved 106133-20-4 408.512 C20H28N2O5S P35348#Alpha-1A adrenergic receptor@P25100#Alpha-1D adrenergic receptor@P35368#Alpha-1B adrenergic receptor Tamsulosin is an alpha adrenoceptor blocker with specificity for the alpha-1A and alpha-1D subtypes, which are more common in the prostate and submaxillary tissue.1 The final subtype, alpha-1B, are most common in the aorta and spleen.1 Tamsulosin binds to alpha-1A receptors 3.9-38 times more selectively than alpha-1B and 3-20 times more selectively than alpha-1D.1 This selectivity allows for a significant effect on urinary flow with a reduced incidence of adverse reactions like orthostatic hypotension.1 D05MBZ DB00708 Sufentanil small molecule approved 56030-54-7 386.551 C22H30N2O2S P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor Effect on the Central Nervous System (CNS) D0D8DD DB00709 Lamivudine small molecule approved 134678-17-4 229.256 C8H11N3O3S Q72547#Reverse transcriptase/RNaseH@Q05486#Protein P Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1) and hepatitis B (HBV) to disrupt viral DNA synthesis. When phosphorylated, lamivudine can form active metabolites that compete for incorporation into viral DNA. Via DNA incorporation, lamivudine metabolites competitively inhibit the activity of the HIV reverse transcriptase enzyme and act as a chain terminator of DNA synthesis. Due to the lack of a 3'-OH group, incorporated nucleoside analogues prevent the formation of a 5' to 3' phosphodiester linkage that is essential for DNA chain elongation. D07TQV DB00710 Ibandronate small molecule approved 114084-78-5 319.2289 C9H23NO7P2 O95749#Geranylgeranyl pyrophosphate synthase@P14324#Farnesyl pyrophosphate synthase Ibandronate is a nitrogen containing bisphosphonate used to treat and prevent osteoporosis in postmenopausal women.11,12 The therapeutic index is wide as overdoses are not especially toxic, and the duration of action is long as the half life can be up to 157 hours.11,12 Patients should be counselled regarding the risk of upper GI adverse reactions, hypocalcemia, musculoskeletal pain, osteonecrosis of the jaw, atypical fractures of the femur, and severe renal impairment.11,12 D08SJZ DB00711 Diethylcarbamazine small molecule approved 90-89-1 199.2932 C10H21N3O P09917#Arachidonate 5-lipoxygenase@P23219#Prostaglandin G/H synthase 1 Diethylcarbamazine is an anthelmintic drug that does not resemble other antiparasitic compounds. It is a synthetic organic compound which is highly specific for several parasites and does not contain any toxic metallic elements. D06RCB DB00712 Flurbiprofen small molecule approved 5104-49-4 244.2609 C15H13FO2 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Flurbiprofen, a nonsteroidal anti-inflammatory agent (NSAIA) of the propionic acid class, is structually and pharmacologically related to fenoprofen, ibuprofen, and ketoprofen, and has similar pharmacological actions to other prototypica NSAIAs. Flurbiprofen exhibits antiinflammatory, analgesic, and antipyretic activities. The commercially available flurbiprofen is a racemic mixture of (+)S- and (-) R-enantiomers. The S-enantiomer appears to possess most of the anti-inflammatory, while both enantiomers may possess analgesic activity. D0A1PX DB00713 Oxacillin small molecule approved 66-79-5 401.436 C19H19N3O5S A0A0E1R3H3#Penicillin-binding protein 3@P46059#Solute carrier family 15 member 1@D6R448#Penicillin-binding protein 2@Q16348#Solute carrier family 15 member 2 Oxacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Oxacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Oxacillin results from the inhibition of cell wall synthesis and is mediated through Oxacillin binding to penicillin binding proteins (PBPs). Oxacillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. D0MB8I DB00714 Apomorphine small molecule approved 58-00-4 267.3224 C17H17NO2 P18825#Alpha-2C adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P08908#5-hydroxytryptamine receptor 1A@P28223#5-hydroxytryptamine receptor 2A@P41595#5-hydroxytryptamine receptor 2B@P28335#5-hydroxytryptamine receptor 2C@P08913#Alpha-2A adrenergic receptor@P28221#5-hydroxytryptamine receptor 1D@P28222#5-hydroxytryptamine receptor 1B Apomorphine is a dopaminergic agonist that may stimulate regions of the brain involved in motor control.8,11,12 It has a short duration of action and a wide therapeutic index as large overdoses are necessary for significant toxicity.11,12 Patients should be counselled regarding the risk of nausea, vomiting, daytime somnolence, hypotension, oral mucosal irritation, falls, hallucinations, psychotic-like behaviour, impulsive behaviour, withdrawal hyperpyrexia, and prolongation of the QT interval.p11,12 D0H6QU DB00715 Paroxetine small molecule approved 61869-08-7 329.3654 C19H20FNO3 P31645#Sodium-dependent serotonin transporter@P23975#Sodium-dependent noradrenaline transporter@P28223#5-hydroxytryptamine receptor 2A@P70174#Histamine H1 receptor@P41595#5-hydroxytryptamine receptor 2B Paroxetine treats the symptoms of depression, various anxiety disorders, posttraumatic stress disorder, obsessive-compulsive disorder, and the vasomotor symptoms of menopause via the inhibition of serotonin reuptake.26,29,30 The onset of action of paroxetine is reported to be approximately 6 weeks.18 D06GDY DB07565 Chloramphenicol succinate small molecule approved 3544-94-3 423.202 C15H16Cl2N2O8 P24093#Dr hemagglutinin structural subunit Chloramphenicol succinate is a prodrug of chloramphenicol, which binds to bacterial ribosomes and prevents translation.1,6,7 It has a narrow therapeutic index8 and a moderate duration of action.10 Patients should be counselled regarding the risk of serious fatal blood dyscrasias.10 DB07776 Flavone small molecule approved 525-82-6 222.2387 C15H10O2 P0A3R9#Neocarzinostatin@P11474#Steroid hormone receptor ERR1@O95718#Steroid hormone receptor ERR2@Q16678#Cytochrome P450 1B1 Not Available DB00716 Nedocromil small molecule approved 69049-73-6 371.3408 C19H17NO7 Q9Y271#Cysteinyl leukotriene receptor 1@Q9NS75#Cysteinyl leukotriene receptor 2@P21462#fMet-Leu-Phe receptor@Q13258#Prostaglandin D2 receptor@P07900#Heat shock protein HSP 90-alpha Nedocromil is a anti-inflammatory agent and can be administered directly to the bronchial mucosa. It has significant inhibitory effect on allergen-induced early and late asthmatic reactions and on bronchial hyperresponsiveness. DB00717 Norethisterone small molecule approved 68-22-4 298.4192 C20H26O2 P06401#Progesterone receptor@P10275#Androgen receptor@P04150#Glucocorticoid receptor Norethisterone is a synthetic oral progestin used for contraception or to treat other hormone-related conditions such as menopausal symptoms and endometriosis. As a synthetic progestin, norethisterone acts similarly to endogenous progesterone but with a much higher potency - it acts at the pelvic level to alter cervical and endometrial function, as well as via the inhibition of pituitary hormones that play a role in follicular maturation and ovulation.14 A small increase in the risk of developing breast cancer has been observed in patients using combined oral contraceptives, with some evidence also implicating progestin-only pills - patients starting hormonal contraception should be advised of this risk and should employ routine breast self-examinations to check for evidence of any developing masses.14 DB00718 Adefovir dipivoxil small molecule approved 142340-99-6 501.4705 C20H32N5O8P Adefovir dipivoxil a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). The concentration of adefovir that inhibited 50% of viral DNA synthesis (IC50) in vitro ranged from 0.2 to 2.5 μM in HBV transfected human hepatoma cell lines. The combination of adefovir with lamivudine showed additive anti-HBV activity. DB00719 Azatadine small molecule approved 3964-81-6 290.4021 C20H22N2 P70174#Histamine H1 receptor Azatadine is an antihistamine, related to cyproheptadine, with anti-serotonin, anticholinergic (drying), and sedative effects. Azatadine is in the same class of drugs as chlorpromazine (Thorazine) and trifluoperazine (Stelazine); however, unlike the other drugs in this class, azatadine is not used clinically as an anti-psychotic. Antihistamines antagonize the vasodilator effect of endogenously released histamine, especially in small vessels, and mitigate the effect of histamine which results in increased capillary permeability and edema formation. As consequences of these actions, antihistamines antagonize the physiological manifestations of histamine release in the nose following antigen-antibody interaction, such as congestion related to vascular engorgement, mucosal edema, and profuse, watery secretion, and irritation and sneezing resulting from histamine action on afferent nerve terminals. D0N7AD DB00720 Clodronic acid small molecule approved 10596-23-3 244.892 CH4Cl2O6P2 P12235#ADP/ATP translocase 1@P05141#ADP/ATP translocase 2@P12236#ADP/ATP translocase 3 Clodronic acid is a first generation bisphosphonate that inhibits osteoclast mediated bone resorption.8 It has a wide therapeutic index as a large overdose is required for significant toxicity and a long duration of action due to the slow release from bone.8 Patients should be counselled regarding the risk of hypocalcemia, hypovolemia, renal insufficiency, transient hyperphosphatemia, and transient hyperparathyroidism.8 DB00721 Procaine small molecule approved 59-46-1 236.3101 C13H20N2O2 Q9Y5Y9#Sodium channel protein type 10 subunit alpha@Q8TCU5#Glutamate receptor ionotropic, NMDA 3A@P46098#5-hydroxytryptamine receptor 3A@Q01959#Sodium-dependent dopamine transporter@Q15822#Neuronal acetylcholine receptor subunit alpha-2@P47712#Cytosolic phospholipase A2@Q86U10#60 kDa lysophospholipase Procaine is an anesthetic agent indicated for production of local or regional anesthesia, particularly for oral surgery. Procaine (like cocaine) has the advantage of constricting blood vessels which reduces bleeding, unlike other local anesthetics like lidocaine. Procaine is an ester anesthetic. It is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-aminobenzoic acid (PABA), which is then excreted by the kidneys into the urine. D0TZ1G DB00722 Lisinopril small molecule approved 76547-98-3 405.4879 C21H31N3O5 P12821#Angiotensin-converting enzyme@P00797#Renin Lisinopril is an angiotensin converting enzyme inhibitor used to treat hypertension, heart failure, and myocardial infarction.8,9,10 Lisinopril is not a prodrug, and functions by inhibition of angiotensin converting enzyme as well as the renin angiotensin aldosterone system.3,4,5 It has a wide therapeutic index and a long duration of action as patients are generally given 10-80mg daily.8,9,10 D07HGR DB00723 Methoxamine small molecule approved 390-28-3 211.2576 C11H17NO3 P35348#Alpha-1A adrenergic receptor@P25100#Alpha-1D adrenergic receptor@P35368#Alpha-1B adrenergic receptor Methoxamine is a potent sympathomimetic amine that increases both systolic and diastolic blood pressure. Methoxamine is indicated for prevention and treatment of the acute hypotensive state occurring with spinal anesthesia. It is also indicated as adjunctive treatment of hypotension due to hemorrhage, reactions to medications, surgical complications, and shock associated with brain damage due to trauma or tumor. Methoxamine acts on both α1-adrenergic receptors but appears to have no effect on β-adrenergic receptors. It acts by increasing the force of the heart's pumping action as well as constricting peripheral blood vessels. D09GYT DB00724 Imiquimod small molecule approved 99011-02-6 240.3036 C14H16N4 Q9NYK1#Toll-like receptor 7@Q9NR97#Toll-like receptor 8 Imiquimod is an immune response modifier that acts as a toll-like receptor 7 agonist. Imiquimod is commonly used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production. It is not used on warts inside the vagina, penis, or rectum. Imiquimod is also used to treat a skin condition of the face and scalp called actinic keratoses. Imiquimod can also be used to treat certain types of skin cancer called superficial basal cell carcinoma. Imiquimod is particularly useful on areas where surgery or other treatments may be difficult, complicated or otherwise undesirable, especially the face and lower legs. D06CTE DB00725 Homatropine methylbromide small molecule approved 80-49-9 370.281 C17H24BrNO3 P08172#Muscarinic acetylcholine receptor M2@P11229#Muscarinic acetylcholine receptor M1@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5@P20309#Muscarinic acetylcholine receptor M3 Homatropine methylbromide belongs to the group of medicines called anti-muscarinics. Homatropine is used to treat duodenal or stomach ulcers or intestine problems. It can be used together with antacids or other medicine in the treatment of peptic ulcer. It may also be used to prevent nausea, vomiting, and motion sickness. DB00726 Trimipramine small molecule approved 739-71-9 294.4338 C20H26N2 P31645#Sodium-dependent serotonin transporter@P23975#Sodium-dependent noradrenaline transporter@Q01959#Sodium-dependent dopamine transporter@P28223#5-hydroxytryptamine receptor 2A@P08908#5-hydroxytryptamine receptor 1A@P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P70174#Histamine H1 receptor@P28335#5-hydroxytryptamine receptor 2C Trimipramine is a tricyclic antidepressant. It was thought that tricyclic antidepressants work by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitised (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route. They are also effective in migraine prophylaxis, but not in abortion of acute migraine attack. The mechanism of their anti-migraine action is also thought to be serotonergic. D00HZV DB00727 Nitroglycerin small molecule approved 55-63-0 227.0865 C3H5N3O9 P16066#Atrial natriuretic peptide receptor 1 Nitroglycerin causes the relaxation of vascular smooth muscles, causing arteriolar and venous dilatation. It reduces cardiac preload and afterload and reduces coronary artery spasm, decreasing systemic vascular resistance as well as systolic and diastolic blood pressure.20 The reduction of cardiac work by nitroglycerin is thought to cause the most relief of anginal symptoms, with some contributions from arteriolar dilatation effects.13 D07YDE DB00728 Rocuronium small molecule approved 143558-00-3 529.7742 C32H53N2O4 Q15822#Neuronal acetylcholine receptor subunit alpha-2@P08172#Muscarinic acetylcholine receptor M2@P46098#5-hydroxytryptamine receptor 3A Neuromuscular blocking agents are drugs that cause skeletal muscle relaxation primarily by causing a decreased response to the neurotransmitter acetylcholine (ACh) at the myoneural (neuromuscular) junction of skeletal muscle. At that site, ACh normally produces electrical depolarization of the postjunctional membrane of motor end-plate, which leads to conduction of muscle action potential and subsequently induces skeletal muscle contraction. Neuromuscular agents are classified as depolarizing or nondepolarizing. Rocuronium is a nondepolarizing neuromuscular blocking agent with a rapid to intermediate onset depending on dose and intermediate duration. Rocuronium, like vecuronium is longer acting in infants than in children. However, unlike vecuronium, rocuronium retains the characteristics of an intermediate-acting NMBD in infants. D0L5CZ DB00730 Thiabendazole small molecule approved 148-79-8 201.248 C10H7N3S P00363#Fumarate reductase flavoprotein subunit Thiabendazole is a fungicide and parasiticide. Thiabendazole is also a chelating agent, which means that it is used medicinally to bind metals in cases of metal poisoning, such as lead poisoning, mercury poisoning or antimony poisoning. Thiabendazole is vermicidal and/or vermifugal against Ascaris lumbricoides ("common roundworm"), Strongyloides stercoralis (threadworm), Necator americanus, Ancylostoma duodenale (hookworm), Trichuris trichiura (whipworm), Ancylostoma braziliense (dog and cat hookworm), Toxocara canis, Toxocara cati (ascarids), and Enterobius vermicularis (pinworm). Thiabendazole also suppresses egg and/or larval production and may inhibit the subsequent development of those eggs or larvae which are passed in the feces. D08QCJ DB00731 Nateglinide small molecule approved 105816-04-4 317.429 C19H27NO3 P37231#Peroxisome proliferator-activated receptor gamma D06PSS DB00732 Atracurium besylate small molecule approved 64228-81-5 1243.49 C65H82N2O18S2 Q15822#Neuronal acetylcholine receptor subunit alpha-2 Atracurium is a nondepolarizing skeletal muscle relaxant. Atracurium can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored to assess degree of muscle relaxation. The duration of neuromuscular block produced by Atracurium is approximately one third to one half the duration of block by d-tubocurarine, metocurine, and pancuronium at initially equipotent doses. As with other nondepolarizing neuromuscular blockers, the time to onset of paralysis decreases and the duration of maximum effect increases with increasing doses of Atracurium. Repeated administration of maintenance doses of Atracurium has no cumulative effect on the duration of neuromuscular block if recovery is allowed to begin prior to repeat dosing. Moreover, the time needed to recover from repeat doses does not change with additional doses. Repeat doses can therefore be administered at relatively regular intervals with predictable results. DB00733 Pralidoxime small molecule approved 6735-59-7 137.1592 C7H9N2O P22303#Acetylcholinesterase@P06276#Cholinesterase Pralidoxime is to reactivate cholinesterase (mainly outside of the central nervous system) which has been inactivated by phosphorylation due to an organophosphate pesticide or related compound. The destruction of accumulated acetylcholine can then proceed, and neuromuscular junctions will again function normally. Pralidoxime also slows the process of "aging" of phosphorylated cholinesterase to a nonreactivatable form, and detoxifies certain organophosphates by direct chemical reaction. The drug has its most critical effect in relieving paralysis of the muscles of respiration. Because pralidoxime is less effective in relieving depression of the respiratory center, atropine is always required concomitantly to block the effect of accumulated acetylcholine at this site. Pralidoxime relieves muscarinic signs and symptoms, salivation, bronchospasm, etc., but this action is relatively unimportant since atropine is adequate for this purpose. DB00734 Risperidone small molecule approved 106266-06-2 410.4845 C23H27FN4O2 P28223#5-hydroxytryptamine receptor 2A@P35368#Alpha-1B adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P35348#Alpha-1A adrenergic receptor@P18825#Alpha-2C adrenergic receptor@P70174#Histamine H1 receptor@P28335#5-hydroxytryptamine receptor 2C@P28221#5-hydroxytryptamine receptor 1D@P08908#5-hydroxytryptamine receptor 1A@P34969#5-hydroxytryptamine receptor 7 The primary action of risperidone is to decrease dopaminergic and serotonergic pathway activity in the brain, therefore decreasing symptoms of schizophrenia and mood disorders.3,4 D01AZG DB00735 Naftifine small molecule approved 65472-88-0 287.3981 C21H21N Q92206#Squalene monooxygenase Naftifine is a synthetic, broad spectrum, antifungal agent and allylamine derivative. The following in vitro data are available, but their clinical significance is unknown. Naftifine has been shown to exhibit fungicidal activity in vitro against a broad spectrum of organisms including Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum, and Microsporum canis, Microsporum audouini, and Microsporum gypseum; and fungistatic activity against Candida species including Candida albicans. However it is only used to treat the organisms listed in the indications. D00HPK DB00736 Esomeprazole small molecule approved 119141-88-7 345.416 C17H19N3O3S P20648#Potassium-transporting ATPase alpha chain 1 Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), the healing of erosive esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase at the secretory surface of the gastric parietal cell. By doing so, it inhibits acid secretion into the gsatric lumen. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus. D0C6DT DB00737 Meclizine small molecule approved 569-65-3 390.948 C25H27ClN2 P70174#Histamine H1 receptor@Q14994#Nuclear receptor subfamily 1 group I member 3 Meclizine works on the higher centres of the brain to reduce nausea, vomiting, or vertigo. It is effective against nausea and vomiting arising from many causes, including motion sickness and disorders affecting the vestibular system. The onset of action of meclizine is about 1 hour, with effects lasting between 8 to 24 hours.4 Meclizine is reported to cause drowsiness due to its anticholinergic actions.5 D0T1XW DB00738 Pentamidine small molecule approved 100-33-4 340.4195 C19H24N4O2 O14717#tRNA (cytosine(38)-C(5))-methyltransferase Pentamidine is an antiprotozoal agent. It is an aromatic diamidine, and is known to have activity against Pneumocystis carinii. The exact nature of its antiprotozoal action is unknown. in vitro studies with mammalian tissues and the protozoan Crithidia oncopelti indicate that the drug interferes with nuclear metabolism producing inhibition of the synthesis of DNA, RNA, phospholipids and proteins. Little is known about the drug's pharmacokinetics. The medication is also useful in Leishmaniasis and in prophylaxis against sleeping sickness caused by Trypanosoma brucei gambiense. Hydration before treatment lessens the incidence and severity of side effects, which include liver or kidney dysfunction, hypertension, hypotension, hypoglycemia, hypocalemia, leukopenia, thrombcytopenia, anemia, and allergic reaction. It is generally well-tolerated. D05EAM DB00739 Hetacillin small molecule approved 3511-16-8 389.469 C19H23N3O4S P0A3M6#Penicillin-binding protein 2B@Q8DR59#Penicillin-binding protein 1A@Q7CRA4#Penicillin-binding protein 1b Hetacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Hetacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Hetacillin results from the inhibition of cell wall synthesis and is mediated through Hetacillin binding to penicillin binding proteins (PBPs). D0W7RJ DB00740 Riluzole small molecule approved 1744-22-5 234.198 C8H5F3N2OS Q14524#Sodium channel protein type 5 subunit alpha@Q9UPY5#Cystine/glutamate transporter Riluzole, a member of the benzothiazole class, is indicated for the treatment of patients with amyotrophic lateral sclerosis (ALS). Riluzole extends survival and/or time to tracheostomy. It is also neuroprotective in various in vivo experimental models of neuronal injury involving excitotoxic mechanisms. The etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are not known, although a number of hypotheses have been advanced. One hypothesis is that motor neurons, made vulnerable through either genetic predisposition or environmental factors, are injured by glutamate. In some cases of familial ALS the enzyme superoxide dismutase has been found to be defective. D0H0KB DB00741 Hydrocortisone small molecule approved 50-23-7 362.4599 C21H30O5 P04150#Glucocorticoid receptor@P04083#Annexin A1 Hydrocortisone binds to the glucocorticoid receptor leading to downstream effects such as inhibition of phospholipase A2, NF-kappa B, other inflammatory transcription factors, and the promotion of anti-inflammatory genes.10 Hydrocortisone has a wide therapeutic index8 and a moderate duration of action.1,6 Patients should stop taking the medication if irritation or sensitization occurs.14,15,16,17,18,19 D0KR5B DB00742 Mannitol small molecule approved 69-65-8 182.1718 C6H14O6 D0P7EK DB00743 Gadobenic acid small molecule approved 113662-23-0 667.73 C22H28GdN3O11 Gadobenate dimeglumine shares the pharmacokinetic properties of the ECF contrast agent gadopentetate dimeglumine; however, gadobenate differs in that is also selectively taken-up by hepatocytes and excreted via the bile (up to 5% of dose). The elimination half-life of gadobenate dimeglumine is approximately 1 hour. It is not metabolized. DB00744 Zileuton small molecule approved 111406-87-2 236.29 C11H12N2O2S P09917#Arachidonate 5-lipoxygenase Zileuton is an asthma drug that differs chemically and pharmacologically from other antiasthmatic agents. It blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway. Current data indicates that asthma is a chronic inflammatory disorder of the airways involving the production and activity of several endogenous inflammatory mediators, including leukotrienes. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, are derived from the initial unstable product of arachidonic acid metabolism, leukotriene A4 (LTA4), and can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients. In humans, pretreatment with zileuton attenuated bronchoconstriction caused by cold air challenge in patients with asthma. D09JUG DB00745 Modafinil small molecule approved 68693-11-8 273.35 C15H15NO2S Q01959#Sodium-dependent dopamine transporter@P35368#Alpha-1B adrenergic receptor Modafinil is a stimulant drug marketed as a 'wakefulness promoting agent' and is one of the stimulants used in the treatment of narcolepsy. Narcolepsy is caused by dysfunction of a family of wakefulness-promoting and sleep-suppressing peptides, the orexins, whose neurons are activated by modafinil. The prexin neuron activation is associated with psychoactivation and euphoria. Modafinil is not indicated for complaints of lack of energy or fatigue; but it appears to be very helpful for some patients. Also, it has been used in the treatment of hypersomnia, a disorder in which patients lack the capacity for meaningful sleep and may require ten or more hours per day. Recent studies have have found that modafinil may help recovering cocaine addicts fight their addiction. D07HQC DB00746 Deferoxamine small molecule approved 70-51-9 560.684 C25H48N6O8 P05067#Amyloid beta A4 protein Deferoxamine, otherwise known as desferrioxamine or desferal, is a chelating agent used to remove excess iron or aluminum from the body. It acts by binding free iron or aluminum in the bloodstream and enhancing its elimination in the urine. By removing excess iron or aluminum, the agent reduces the damage done to various organs and tissues, such as the liver. DB00747 Scopolamine small molecule approved 51-34-3 303.3529 C17H21NO4 P20309#Muscarinic acetylcholine receptor M3@P08172#Muscarinic acetylcholine receptor M2@P43681#Neuronal acetylcholine receptor subunit alpha-4@P17787#Neuronal acetylcholine receptor subunit beta-2@P14410#Sucrase-isomaltase, intestinal D0B7YT DB00748 Carbinoxamine small molecule approved 486-16-8 290.788 C16H19ClN2O P70174#Histamine H1 receptor Carbinoxamine is a first generation antihistamine of the ethanolamine class. Ethanolamine antihistamines have significant antimuscarinic activity and produce marked sedation in most patients. In addition to the usual allergic symptoms, the drug also treats irritant cough and nausea, vomiting, and vertigo associated with motion sickness. It also is used commonly to treat drug-induced extrapyramidal symptoms as well as to treat mild cases of Parkinson's disease. Rather than preventing the release of histamine, as do cromolyn and nedocromil, carbinoxamine competes with free histamine for binding at HA-receptor sites. Carbinoxamine competitively antagonizes the effects of histamine on HA-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Ethanolamine derivatives have greater anticholinergic activity than do other antihistamines, which probably accounts for the antidyskinetic action of carbinoxamine. D00FGV DB00749 Etodolac small molecule approved 41340-25-4 287.3535 C17H21NO3 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1@P19793#Retinoic acid receptor RXR-alpha Etodolac is an anti-inflammatory agent with analgesic and antipyretic properties. It is used to treat osteoarthritis, rheumatoid arthritis and control acute pain. The therapeutic effects of etodolac are achieved via inhibition of the synthesis of prostaglandins involved in fever, pain, swelling and inflammation. Etodolac is administered as a racemate. As with other NSAIDs, the S-form has been shown to be active while the R-form is inactive. Both enantiomers are stable and there is no evidence of R- to S- conversion in vivo. D0N1WU DB00750 Prilocaine small molecule approved 721-50-6 220.3107 C13H20N2O Q14524#Sodium channel protein type 5 subunit alpha Prilocaine binds to the intracellular surface of sodium channels which blocks the subsequent influx of sodium into the cell. Action potential propagation and never function is, therefore, prevented. This block is reversible and when the drug diffuses away from the cell, sodium channel function is restored and nerve propagation returns. D06LYG DB00751 Epinastine small molecule approved 80012-43-7 249.3104 C16H15N3 P70174#Histamine H1 receptor@P25021#Histamine H2 receptor@P35348#Alpha-1A adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P28223#5-hydroxytryptamine receptor 2A@P34969#5-hydroxytryptamine receptor 7 Epinastine is an antihistamine and an inhibitor of histamine release from the mast cell for topical administration to the eyes. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis. Epinastine is a topically active, direct H1-receptor antagonist and an inhibitor of the release of histamine from the mast cell. Epinastine is selective for the histamine H1-receptor and has affinity for the histamine H2 receptor. Epinastine also possesses affinity for the a1-, a2-, and 5-HT2 -receptors. Epinastine does not penetrate the blood/brain barrier and, therefore, is not expected to induce side effects of the central nervous system. D0DV3O DB00752 Tranylcypromine small molecule approved 155-09-9 133.194 C9H11N P27338#Amine oxidase [flavin-containing] B@P21397#Amine oxidase [flavin-containing] A Tranylcypromine belongs to a class of antidepressants called monoamine oxidase inhibitors (MAOIs). Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor with a rapid onset of activity. MAO is an enzyme that catalyzes the oxidative deamination of a number of amines, including serotonin, norepinephrine, epinephrine, and dopamine. Two isoforms of MAO, A and B, are found in the body. MAO-A is mainly found within cells located in the periphery and catalyzes the breakdown of serotonin, norepinephrine, epinephrine, dopamine and tyramine. MAO-B acts on phenylethylamine, norepinephrine, epinephrine, dopamine and tyramine, is localized extracellularly and is found predominantly in the brain. While the mechanism of MAOIs is still unclear, it is thought that they act by increasing free serotonin and norepinephrine concentrations and/or by altering the concentrations of other amines in the CNS. It has been postulated that depression is caused by low levels of serotonin and/or norepinephrine and that increasing serotonergic and norepinephrinergic neurotransmission results in relief of depressive symptoms. MAO A inhibition is thought to be more relevant to antidepressant activity than MAO B inhibition. Selective MAO B inhibitors, such as selegiline, have no antidepressant effects. D0H0HJ DB00753 Isoflurane small molecule approved 26675-46-7 184.492 C3H2ClF5O P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P98194#Calcium-transporting ATPase type 2C member 1@P23415#Glycine receptor subunit alpha-1@P42261#Glutamate receptor 1@Q09470#Potassium voltage-gated channel subfamily A member 1@P30049#ATP synthase subunit delta, mitochondrial@P0DP23#Calmodulin@P43681#Neuronal acetylcholine receptor subunit alpha-4@P17787#Neuronal acetylcholine receptor subunit beta-2 Isoflurane is a general inhalation anesthetic used for induction and maintenance of general anesthesia. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. It does so by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential. D0DP6L DB00754 Ethotoin small molecule approved 86-35-1 204.2252 C11H12N2O2 Q14524#Sodium channel protein type 5 subunit alpha@O75469#Nuclear receptor subfamily 1 group I member 2 Ethotoin is a hydantoin derivative and anticonvulsant. Ethotoin exerts an antiepileptic effect without causing general central nervous system depression. The mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges. D05EPM DB00755 Tretinoin small molecule approved 302-79-4 300.442 C20H28O2 P28702#Retinoic acid receptor RXR-beta@P13631#Retinoic acid receptor gamma@P48443#Retinoic acid receptor RXR-gamma Tretinoin, also known as all-trans-retinoic acid (ATRA), is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis. Tretinoin also represents the class of anticancer drugs called differentiating agents and is used in the treatment of acute promyelocytic leukemia (APL). D02DGU DB00756 Hexachlorophene small molecule approved 70-30-4 406.904 C13H6Cl6O2 P06149#D-lactate dehydrogenase@P03372#Estrogen receptor@P00367#Glutamate dehydrogenase 1, mitochondrial Hexachlorophene, a detergent cleanser, is an antibacterial sudsing emulsion for topical administration. It is a bacteriostatic cleansing agent. It cleanses the skin thoroughly and has bacteriostatic action against staphylococci and other gram-positive bacteria. Cumulative antibacterial action develops with repeated use. Cleansing with alcohol or soaps containing alcohol removes the antibacterial residue. D0ZX2G DB00757 Dolasetron small molecule approved 115956-12-2 324.38 C19H20N2O3 P46098#5-hydroxytryptamine receptor 3A Dolasetron is a highly specific and selective serotonin 5-HT3 receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors. It is structurally and pharmacologically related to other 5-HT3 receptor agonists. The serontonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. It is suggested that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting. D00YLW DB00758 Clopidogrel small molecule approved 113665-84-2 321.822 C16H16ClNO2S Q9H244#P2Y purinoceptor 12 Clopidogrel is a prodrug of a platelet inhibitor used to reduce the risk of myocardial infarction and stroke.3,9 It has a long duration of action as it is taken once daily and a large therapeutic window as it is given in doses of 75-300mg daily.9 D0N0TZ DB00759 Tetracycline small molecule approved 60-54-8 444.4346 C22H24N2O8 Q9UM07#Protein-arginine deiminase type-4@P04156#Major prion protein@P0AG59#30S ribosomal protein S14@P0A7U3#30S ribosomal protein S19@P0A7V3#30S ribosomal protein S3@P0A7W7#30S ribosomal protein S8@P02359#30S ribosomal protein S7 Tetracycline is a short-acting antibiotic that inhibits bacterial growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. It also binds to some extent to the 50S ribosomal subunit. This binding is reversible in nature. Additionally tetracycline may alter the cytoplasmic membrane of bacteria causing leakage of intracellular contents, such as nucleotides, from the cell. D08NQZ DB00760 Meropenem small molecule approved 96036-03-2 383.463 C17H25N3O5S P24228#D-alanyl-D-alanine carboxypeptidase DacB Meropenem is a broad-spectrum carbapenem antibiotic. It is active against Gram-positive and Gram-negative bacteria. Meropenem exerts its action by penetrating bacterial cells readily and interfering with the synthesis of vital cell wall components, which leads to cell death. D0O5FY DB00761 Potassium chloride small molecule approved 7447-40-7 74.551 ClK P55011#Solute carrier family 12 member 2@Q13621#Solute carrier family 12 member 1@Q9H2X9#Solute carrier family 12 member 5@Q9UHW9#Solute carrier family 12 member 6@Q9Y666#Solute carrier family 12 member 7@Q9UP95#Solute carrier family 12 member 4 The potassium ion is in the principle intracellular cation of most body tissues. Potassium ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity, the transmission of nerve impulses, the contraction of cardiac, skeletal and smooth muscle, and the maintenance of normal renal function. The intracellular concentration of potassium is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane. Potassium is a normal dietary constituent and under steady-state conditions the amount of potassium absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of potassium is 50 to 100 mEq per day. Potassium depletion will occur whenever the rate of potassium loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of potassium intake. Such depletion usually develops as a consequence of therapy with diuretics, primarily or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of potassium in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Potassium depletion due to these causes is usually accompanied by concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Potassium depletion may produce weakness, fatigue, disturbances of cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and, in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine. If potassium depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, e.g., where the patient requires long-term diuretic therapy, supplemental potassium in the form of high potassium food or potassium chloride may be able to restore normal potassium levels. In rare circumstances (e.g., patients with renal tubular acidosis) potassium depletion may be associated with metabolic acidosis and hyperchloremia. In such patients, potassium replacement should be accomplished with potassium salts other than the chloride, such as potassium bicarbonate, potassium citrate, potassium acetate, or potassium gluconate. DB00762 Irinotecan small molecule approved 97682-44-5 586.678 C33H38N4O6 Q969P6#DNA topoisomerase I, mitochondrial@Q06AK7#DNA topoisomerase 1 Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is a semisynthetic derivative of camptothecin. Camptothecins interact specifically with topoisomerase I, an enzyme in the cell nucleus that regulates DNA topology and facilitates nuclear processes such as DNA replication, recombination, and repair. During these processes, topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks, allowing single DNA strands to pass through the break. The 3'-DNA terminus of the broken DNA strands bind covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After the DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the chemically unaltered topoisomers that allow transcription to proceed. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks. The precise contribution of SN-38 to the activity of irinotecan in humans is not known. Irinotecan is cell cycle phase-specific (S-phase). D07HOB DB00763 Methimazole small molecule approved 60-56-0 114.169 C4H6N2S P07202#Thyroid peroxidase Methimazole inhibits the synthesis of thyroid hormones resulting in an alleviation of hyperthyroidism.1819 Onset of action occurs within 12 to 18 hours, and its duration of action is 36 to 72 hours, likely due to concentration of methimazole and some metabolites within the thyroid gland after administration.11 D0S4BR DB00765 Metyrosine small molecule approved 672-87-7 195.2151 C10H13NO3 P07101#Tyrosine 3-monooxygenase In patients with pheochromocytoma, who produce excessive amounts of norepinephrine and epinephrine, administration of one to four grams of metyrosine per day has reduced catecholamine biosynthesis from about 35 to 80 percent as measured by the total excretion of catecholamines and their metabolites (metanephrine and vanillylmandelic acid). The maximum biochemical effect usually occurs within two to three days, and the urinary concentration of catecholamines and their metabolites usually returns to pretreatment levels within three to four days after metyrosine is discontinued. Most patients with pheochromocytoma treated with metyrosine experience decreased frequency and severity of hypertensive attacks with their associated headache, nausea, sweating, and tachycardia. In patients who respond, blood pressure decreases progressively during the first two days of therapy with metyrosine; after withdrawal, blood pressure usually increases gradually to pretreatment values within two to three days. D0B3QM DB00766 Clavulanic acid small molecule approved 58001-44-8 199.1608 C8H9NO5 Clavulanic acid inactivates some beta-lactamase enzymes that are produced by bacteria, therefore preventing enzymatic destruction of amoxicillin. This helps to treat a variety of bacterial infections which would otherwise be resistant to antibiotics without the addition of clavulanic acid.10,11,13 DB00768 Olopatadine small molecule approved 113806-05-6 337.4122 C21H23NO3 P70174#Histamine H1 receptor@P25021#Histamine H2 receptor@Q9Y5N1#Histamine H3 receptor@P23297#Protein S100-A1@P80511#Protein S100-A12@P04271#Protein S100-B@Q99584#Protein S100-A13@P29034#Protein S100-A2 Inflammatory reactions in response to various stimuli are mediated by endogenous mediators and other pro-inflammatory factors. Histamine receptor activation and mast cell degranulation are primary mechanisms that cause inflammatory reactions such as ocular itching, hyperemia, chemosis, eyelid swelling, and tearing of seasonal allergic conjunctivitis.3 Olopatadine is an anti-allergenic molecule and mast cell stabilizer that inhibits the in vivo type 1 immediate hypersensitivity reaction.10 By blocking the effects of histamine, olopatadine works to reduce the symptoms of allergies and inflammation at various sites of administration, including the eyes and nose. It has shown to exert antihistaminic effects in isolated tissues, animal models, and humans.8 Olopatadine also demonstrated dose-dependent inhibition of immunologically-stimulated release of histamine from rat basophilic leukemia cells and human conjunctival mast cells in vitro.3 Olopatadine has a relatively rapid onset of action and prolonged duration, where it was shown to mediate anti-histaminic effects at 5 minutes to 24 hours post-administration.3 D05GPO DB00769 Hydrocortamate small molecule approved 76-47-1 475.6175 C27H41NO6 P04150#Glucocorticoid receptor Hydrocortamate is a synthetic glucocorticoid used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by having different receptors, target cells, and effects. Technically, the term corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and TNF-alpha, the most important of which is the IL-2. Reduced cytokine production limits T cell proliferation. Glucocorticoids also suppress humoral immunity, causing B cells to express lower amounts of IL-2 and IL-2 receptors. This diminishes both B cell clonal expansion and antibody synthesis. The diminished amounts of IL-2 also leads to fewer T lymphocyte cells being activated. D05RXI DB00770 Alprostadil small molecule approved 745-65-3 354.487 C20H34O5 D0I4DQ DB00771 Clidinium small molecule approved 7020-55-5 352.4467 C22H26NO3 P11229#Muscarinic acetylcholine receptor M1 Clidinium is a synthetic anticholinergic agent which has been shown in experimental and clinical studies to have a pronounced antispasmodic and antisecretory effect on the gastrointestinal tract. D0Q1BT DB00772 Malathion small molecule approved 121-75-5 330.358 C10H19O6PS2 P06276#Cholinesterase Malathion is an organophosphate insecticide commonly used to control mosquitos and other flying insects. Pharmaceutically, malathion is used to eliminate head lice. The principal toxicological effect of malathion is cholinesterase inhibition, due primarily to malaoxon and to phosphorus thionate impurities. D0K3LW DB00773 Etoposide small molecule approved 33419-42-0 588.5566 C29H32O13 P11388#DNA topoisomerase 2-alpha@Q02880#DNA topoisomerase 2-beta D0B7EB DB00774 Hydroflumethiazide small molecule approved 135-09-1 331.292 C8H8F3N3O4S2 Q13621#Solute carrier family 12 member 1@P43166#Carbonic anhydrase 7@Q16790#Carbonic anhydrase 9@P05023#Sodium/potassium-transporting ATPase subunit alpha-1@Q12791#Calcium-activated potassium channel subunit alpha-1@P00915#Carbonic anhydrase 1@P00918#Carbonic anhydrase 2@P22748#Carbonic anhydrase 4@O43570#Carbonic anhydrase 12 Hydroflumethiazide is an oral thiazide used to treat hypertension and edema. High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. High blood pressure may also increase the risk of heart attacks. Like other thiazides, Hydroflumethiazide promotes water loss from the body (diuretics). Thiazides inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. D00WAM DB00775 Tirofiban small molecule approved 144494-65-5 440.597 C22H36N2O5S P08514#Integrin alpha-IIb@P05106#Integrin beta-3 Tirofiban prevents the blood from clotting during episodes of chest pain or a heart attack, or while the patient is undergoing a procedure to treat a blocked coronary artery. It is a non-peptide antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, and inhibits platelet aggregation. When administered intravenously, tirofiban inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner. When given according to the recommended regimen, >90% inhibition is attained by the end of the 30-minute infusion. Tirofiban has been recently shown in patients with unstable angina to reduce ischemic events at 48 hours following infusion when compared to standard heparin therapy. D0BN9X DB00776 Oxcarbazepine small molecule approved 28721-07-5 252.268 C15H12N2O2 Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha@Q9NY72#Sodium channel subunit beta-3@Q8IWT1#Sodium channel subunit beta-4 Oxcarbazepine is an anticonvulsant drug that reduces the incidence of seizures in epilepsy by inhibiting abnormal electrical activity in the brain.10,11,12 D0QL3P DB00777 Propiomazine small molecule approved 362-29-8 340.482 C20H24N2OS P70174#Histamine H1 receptor@P35348#Alpha-1A adrenergic receptor@P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C Although propiomazine is a phenothiazine, it is not used as an antipsychotic. It posesses antihistamine effects and is mostly used as a sedative in treating insomnia. D0R9ZB DB00778 Roxithromycin small molecule approved 80214-83-1 837.0465 C41H76N2O15 P0A7J6#50S ribosomal protein L10 Roxithromycin has the following antibacterial spectrum in vitro: Streptococcus agalactiae, Streptococcus pneumoniae (Pneumococcus), Neisseria meningitides (Meningococcus), Listeria monocytogenes, Mycoplasma pneumoniae, Chlamydia trachomatis, Ureaplasma urealyticum, Legionella pneumophila, Helicobacter (Campylobacter), Gardnerella vaginalis, Bordetella pertussis, Moraxella catarrhalis (Branhamella Catarrhalis), and Haemophilus ducreyi. Roxithromycin is highly concentrated in polymorphonuclear leukocytes and macrophages, achieving intracellular concentrations greater than those outside the cell. Roxithromycin enhances the adhesive and chemotactic functions of these cells which in the presence of infection produce phagocytosis and bacterial lysis. Roxithromycin also possesses intracellular bactericidal activity. D0Y4FL DB00779 Nalidixic acid small molecule approved 389-08-2 232.2353 C12H12N2O3 Nalidixic acid is a quinolone antibacterial agent for oral administration. Nalidixic acid has marked antibacterial activity against gram-negative bacteria including Enterobacter species, Escherichia coli, Morganella Morganii; Proteus Mirabilis, Proteus vulgaris, and Providencia rettgeri. Pseudomonas species are generally resistant to the drug. Nalidixic acid is bactericidal and is effective over the entire urinary pH range. Conventional chromosomal resistance to nalidixic acid taken in full dosage has been reported to emerge in approximately 2 to 14 percent of patients during treatment; however, bacterial resistance to nalidixic acid has not been shown to be transferable via R factor. DB00780 Phenelzine small molecule approved 51-71-8 136.1943 C8H12N2 P21397#Amine oxidase [flavin-containing] A@P27338#Amine oxidase [flavin-containing] B@Q16853#Membrane primary amine oxidase@P80404#4-aminobutyrate aminotransferase, mitochondrial@P24298#Alanine aminotransferase 1@Q8TD30#Alanine aminotransferase 2@Q9UGI5#Glutamic acid decarboxylase The elimination of monoamine oxidase by phenelzine results in the elevation of brain amines such as 2-phenylethylamine which is a metabolite of phenelzine. These amines have then marked effects on the uptake and release of catecholamines and serotonin in nerve endings.7 Phenelzine is shown to elevate brain levels of the gamma-aminobutyric acid (GABA) and alanine (ALA) as well as to inhibit the activity of the transaminases that normally metabolize these amino acids. In preclinical studies, it has been shown to be neuroprotective in cerebral ischemia.3 D0P9AC DB00782 Propantheline small molecule approved 298-50-0 368.4892 C23H30NO3 P11229#Muscarinic acetylcholine receptor M1 Propantheline is an anticholinergic drug, a medication that reduces the effect of acetylcholine, a chemical released from nerves that stimulates muscles, by blocking the receptors for acetylcholine on smooth muscle (a type of muscle). It also has a direct relaxing effect on smooth muscle. Propantheline is used to treat or prevent spasm in the muscles of the gastrointestinal tract in the irritable bowel syndrome. In addition, Propantheline inhibits gastrointestinal propulsive motility and decreases gastric acid secretion and controls excessive pharyngeal, tracheal and bronchial secretions. D0V5ZZ DB00783 Estradiol small molecule approved 50-28-2 272.382 C18H24O2 Q92731#Estrogen receptor beta@O75469#Nuclear receptor subfamily 1 group I member 2@P43681#Neuronal acetylcholine receptor subunit alpha-4@Q99527#G-protein coupled estrogen receptor 1@P00846#ATP synthase subunit a@Q14457#Beclin-1 Estradiol acts on the on the estrogen receptors to relieve vasomotor systems (such as hot flashes) and urogenital symptoms (such as vaginal dryness and dyspareunia).18,19,20 D08QMX DB00784 Mefenamic acid small molecule approved 61-68-7 241.2851 C15H15NO2 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Mefenamic acid, an anthranilic acid derivative, is a member of the fenamate group of nonsteroidal anti-inflammatory drugs (NSAIDs). It exhibits anti-inflammatory, analgesic, and antipyretic activities. Similar to other NSAIDs, mefenamic acid inhibits prostaglandin synthetase. D05FTJ DB00787 Acyclovir small molecule approved 59277-89-3 225.2046 C8H11N5O3 P09252#DNA polymerase catalytic subunit@P09252#DNA polymerase catalytic subunit@P13159#Thymidine kinase Acyclovir is a nucleoside analog that inhibits the action of viral DNA polymerase and DNA replication of different herpesvirus.10,11,12,13,14,15 Acyclovir has a wide therapeutic window as overdose is rare in otherwise healthy patients.11 DB00788 Naproxen small molecule approved 22204-53-1 230.2592 C14H14O3 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2@Q51911#Peptostreptococcal albumin-binding protein Naproxen is an established non-selective NSAID and is useful as an analgesic, anti-inflammatory and antipyretic.5 Similar to other NSAIDs, the pharmacological activity of naproxen can be attributed to the inhibition of cyclo-oxygenase, which in turn reduces prostaglandin synthesis in various tissues and fluids including the synovial fluid, gastric mucosa, and the blood.5 D0DJ1B DB00789 Gadopentetic acid small molecule approved 80529-93-7 547.58 C14H20GdN3O10 P52209#6-phosphogluconate dehydrogenase, decarboxylating Not Available DB00790 Perindopril small molecule approved 82834-16-0 368.4678 C19H32N2O5 P12821#Angiotensin-converting enzyme@Q6FHJ7#Secreted frizzled-related protein 4 Perindopril is a nonsulfhydryl prodrug that is metabolized via first pass effect (62%) and systemic hydrolysis (38%) to perindoprilat, its active metabolite, following oral administration. Perindoprilat lowers blood pressure by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of perindoprilat by causing increased vasodilation and decreased blood pressure. D03KYG DB00791 Uracil mustard small molecule approved 66-75-1 252.098 C8H11Cl2N3O2 Uracil Mustard selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of Uracil Mustard-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. D0J9UN DB00792 Tripelennamine small molecule approved 91-81-6 255.358 C16H21N3 P70174#Histamine H1 receptor Used to treat the effects of colds and allergies. Tripelennamine is an antihistamine. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Tripelennamine is a histamine H1 antagonist. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. D0B4JQ DB00793 Haloprogin small molecule approved 777-11-7 361.391 C9H4Cl3IO Used as a topical ointment or cream in the treatment of Tinea infections. Tinea infections are superficial fungal infections caused by three species of fungi collectively known as dermatophytes (Trichophyton, Microsporum and Epidermophyton). Commonly these infections are named for the body part affected, including tinea corporis (general skin), tinea cruris (groin), and tinea pedis (feet). D06ZAY DB00794 Primidone small molecule approved 125-33-7 218.2518 C12H14N2O2 P47869#Gamma-aminobutyric acid receptor subunit alpha-2@P34903#Gamma-aminobutyric acid receptor subunit alpha-3@P48169#Gamma-aminobutyric acid receptor subunit alpha-4@P31644#Gamma-aminobutyric acid receptor subunit alpha-5@Q16445#Gamma-aminobutyric acid receptor subunit alpha-6@P14867#Gamma-aminobutyric acid receptor subunit alpha-1@P43681#Neuronal acetylcholine receptor subunit alpha-4@P36544#Neuronal acetylcholine receptor subunit alpha-7@P42262#Glutamate receptor 2@Q13002#Glutamate receptor ionotropic, kainate 2 Primidone alters sodium and calcium channel transport, reducing the frequency of nerve firing, which may be responsible for its effect on convulsions and essential tremor.4 Primidone has a wide therapeutic window as doses of 50-1000mg/day were effective.4 Patients should be counselled regarding the risk of status epilepticus with abrupt cessation of primidone.15 D0U5RT DB00795 Sulfasalazine small molecule approved 599-79-1 398.393 C18H14N4O5S P09917#Arachidonate 5-lipoxygenase@P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1@P37231#Peroxisome proliferator-activated receptor gamma@O15111#Inhibitor of nuclear factor kappa-B kinase subunit alpha@O14920#Inhibitor of nuclear factor kappa-B kinase subunit beta@Q9UPY5#Cystine/glutamate transporter@P24752#Acetyl-CoA acetyltransferase, mitochondrial@P24557#Thromboxane-A synthase@P04054#Phospholipase A2 Sulfasalazine is an anti-inflammatory indicated for the treatment of ulcerative colitis and rheumatoid arthritis. D02ZTJ DB00796 Candesartan cilexetil small molecule approved 145040-37-5 610.671 C33H34N6O6 P30556#Type-1 angiotensin II receptor Candesartan cilexetil is an ARB prodrug that is rapidly converted to candesartan, its active metabolite, during absorption from the gastrointestinal tract. Candesartan confers blood pressure lowering effects by antagonizing the hypertensive effects of angiotensin II via the RAAS. RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from granular cells of the juxtaglomerular apparatus in the kidneys. Renin cleaves circulating angiotensinogen to angiotensin I, which is cleaved by angiotensin converting enzyme (ACE) to angiotensin II. Angiotensin II increases blood pressure by increasing total peripheral resistance, increasing sodium and water reabsorption in the kidneys via aldosterone secretion, and altering cardiovascular structure. Angiotensin II binds to two receptors: type-1 angiotensin II receptor (AT1) and type-2 angiotensin II receptor (AT2). AT1 is a G-protein coupled receptor (GPCR) that mediates the vasoconstrictive and aldosterone-secreting effects of angiotensin II. Studies performed in recent years suggest that AT2 antagonizes AT1-mediated effects and directly affects long-term blood pressure control by inducing vasorelaxation and increasing urinary sodium excretion. Angiotensin receptor blockers (ARBs) are non-peptide competitive inhibitors of AT1. ARBs block the ability of angiotensin II to stimulate pressor and cell proliferative effects. Unlike ACE inhibitors, ARBs do not affect bradykinin-induced vasodilation. The overall effect of ARBs is a decrease in blood pressure. DB00797 Tolazoline small molecule approved 59-98-3 160.2157 C10H12N2 P35348#Alpha-1A adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P70174#Histamine H1 receptor@P25021#Histamine H2 receptor@P18825#Alpha-2C adrenergic receptor@P18089#Alpha-2B adrenergic receptor Tolazoline is a pulmonary vasodilator indicated used to decrease pulmonary vascular resistance (PVR) in persistent pulmonary hypertension of the newborn (PPHN). D03RZV DB00798 Gentamicin small molecule approved 1403-66-3 477.5954 C21H43N5O7 P0A7S3#30S ribosomal protein S12@P00374#Dihydrofolate reductase@P08164#NH(3)-dependent NAD(+) synthetase Not Available D0L9UU DB00799 Tazarotene small molecule approved 118292-40-3 351.462 C21H21NO2S P28702#Retinoic acid receptor RXR-beta@P13631#Retinoic acid receptor gamma@P10826#Retinoic acid receptor beta@P10276#Retinoic acid receptor alpha D0BM5G DB00800 Fenoldopam small molecule approved 67227-56-9 305.756 C16H16ClNO3 P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor@P35348#Alpha-1A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P18825#Alpha-2C adrenergic receptor@P08913#Alpha-2A adrenergic receptor Fenoldopam is an agonist at D1-like dopamine receptors, binds to α2-adrenoceptors, increasing renal blood flow. D0R6BI DB00801 Halazepam small molecule approved 23092-17-3 352.738 C17H12ClF3N2O P28472#Gamma-aminobutyric acid receptor subunit beta-3 Not Available D0Z9VB DB00802 Alfentanil small molecule approved 71195-58-9 416.5172 C21H32N6O3 P35372#Mu-type opioid receptor Alfentanil is a synthetic opioid analgesic. Alfentanil interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, alfentanil exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Alfentanil may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Alfentanil depresses the respiratory centers, depresses the cough reflex, and constricts the pupils. D0G5QB DB00803 Colistin small molecule approved 1066-17-7 1155.455 C52H98N16O13 Colistin is a polymyxin antibiotic agent. Polymyxins are cationic polypeptides that disrupt the bacterial cell membrane through a detergentlike mechanism. With the development of less toxic agents, such as extended-spectrum penicillins and cephalosporins, parenteral polymyxin use was largely abandoned, except for the treatment of multidrug-resistant pulmonary infections in patients with cystic fibrosis. More recently, however, the emergence of multidrug-resistant gram-negative bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii, and the lack of new antimicrobial agents have led to the revived use of the polymyxins. D0K7NQ DB00804 Dicyclomine small molecule approved 77-19-0 309.4867 C19H35NO2 P11229#Muscarinic acetylcholine receptor M1@P20309#Muscarinic acetylcholine receptor M3@P08172#Muscarinic acetylcholine receptor M2 Dicyclomine is an anticholinergic drug used to relax the smooth muscles of the intestines.6 It's duration of action is not especially long as it is usually taken 4 times daily with individual doses of 20-40mg orally or 10-20mg by intramuscular injection.6 Dicyclomine should not be administered intravenously.6 D07XJM DB00805 Minaprine small molecule approved 25905-77-5 298.3828 C17H22N4O P21397#Amine oxidase [flavin-containing] A@P41595#5-hydroxytryptamine receptor 2B@P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P22303#Acetylcholinesterase@P31645#Sodium-dependent serotonin transporter@P11229#Muscarinic acetylcholine receptor M1 Minaprine is an amino-phenylpyridazine antidepressant reported to be relatively free of cardiotoxicity, drowsiness, and weight gain. Similar to other antidepressant treatments, minaprine attenuates the beta-adrenergic receptor function. Studies have also shown that minaprine improves memory consolidation and that repeated drug administration leads to potentiation of this effect. Moreover, the effects of minaprine on memory consolidation are related to its dopaminergic action. D0W8SJ DB00806 Pentoxifylline small molecule approved 6493-05-6 278.307 C13H18N4O3 P29274#Adenosine receptor A2a@P30542#Adenosine receptor A1@P21589#5'-nucleotidase Pentoxifylline, a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine, exhibits hemorheological, anti-oxidative, and anti-inflammatory properties and is traditionally indicated in the treatment of peripheral arterial disease (PAD). In PAD patients with concurrent cerebrovascular and coronary artery diseases, pentoxifylline treatment has occasionally been associated with angina, arrhythmia, and hypotension. Concurrent use with warfarin should be associated with more frequent monitoring of prothrombin times. Also, patients with risk factors complicated by hemorrhages, such as retinal bleeding, peptic ulceration, and recent surgery, should be monitored periodically for bleeding signs.29 D09QEI DB00807 Proparacaine small molecule approved 499-67-2 294.3892 C16H26N2O3 Q9Y5Y9#Sodium channel protein type 10 subunit alpha Proparacaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action. More specifically, proparacaine appears to bind or antagonize the function of voltage gated sodium channels. D0Q7ZG DB00808 Indapamide small molecule approved 26807-65-8 365.835 C16H16ClN3O3S P55017#Solute carrier family 12 member 3 Classified as a sulfonamide diuretic, indapamide is an effective antihypertensive agent and by extension, has shown efficacy in the prevention of target organ damage.2,3 D0H8FH DB00809 Tropicamide small molecule approved 1508-75-4 284.3529 C17H20N2O2 P08173#Muscarinic acetylcholine receptor M4@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3 Tropicamide is an anticholinergic drug and that works by non‐selectively blocking muscarinic receptors to cause mydriasis and cycloplegia. It relaxes the pupillary sphincter to dilate the pupil.1 The onset of tropicamide‐induced mydriasis is about 10 to 15 minutes,3 with optimal effect occurring 25 to 30 minutes post-administration. Mydriasis caused by tropicamide wears off within four to eight hours, but it was seen up to 24 hours in some individuals. Tropicamide hinders accommodation by causing the contraction of the ciliary muscle. The cycloplegic effect occurs within 20 to minutes following administration, with a duration of action of four to 10 hours. Tropicamide can elevate intraocular pressure.1 The ophthalmic use of tropicamide is not typically associated with serious systemic adverse events.5 D09PNY DB00810 Biperiden small molecule approved 514-65-8 311.4611 C21H29NO P11229#Muscarinic acetylcholine receptor M1 Biperiden is a weak peripheral anticholinergic agent. It has, therefore, some antisecretory, antispasmodic and mydriatic effects. In addition, biperiden possesses nicotinolytic activity. The parenteral form of biperiden is an effective and reliable agent for the treatment of acute episodes of extrapyramidal disturbances sometimes seen during treatment with neuroleptic agents. Akathisia, akinesia, dyskinetic tremors, rigor, oculogyric crisis, spasmodic torticollis, and profuse sweating are markedly reduced or eliminated. With parenteral biperiden, these drug-induced disturbances are rapidly brought under control. D0B4TN DB00811 Ribavirin small molecule approved 36791-04-5 244.2047 C8H12N4O5 P20839#Inosine-5'-monophosphate dehydrogenase 1@Q05318#RNA-directed RNA polymerase L@B0B3C9#Genome polyprotein@P12268#Inosine-5'-monophosphate dehydrogenase 2 Ribavirin mediates direct antiviral activity against a number of DNA and RNA viruses by increasing the mutation frequency in the genomes of several RNA viruses. It is a member of the nucleoside antimetabolite drugs that interfere with duplication of the viral genetic material. The drug inhibits the activity of the enzyme RNA dependent RNA polymerase, due to its resemblence to building blocks of the RNA molecules. D0H3WI DB00812 Phenylbutazone small molecule approved 50-33-9 308.3743 C19H20N2O2 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2@Q16647#Prostacyclin synthase Phenylbutazone is a synthetic, pyrazolone derivative. It is a nonhormonal anti-inflammatory, antipyretic compound useful in the management of inflammatory conditions. The apparent analgesic effect is probably related mainly to the compound's anti-inflammatory properties and arise from its ability to reduce production of prostaglandin H and prostacyclin. Prostaglandins act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostacylcin causes vascular constriction platelet disaggregation D07VHR DB00813 Fentanyl small molecule approved 437-38-7 336.4705 C22H28N2O P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor Fentanyl produces strong analgesia through its activation of opioid receptors.Label,6 It has a duration of action of several hours and a wider therapeutic index as patients develop tolerance to opioids.Label Fentanyl is associated with a risk of addiction and abuse and should not be mixed with alcohol or benzodiazepines.Label,15,16,17,18,19,20,21 D0E1WI DB00814 Meloxicam small molecule approved 71125-38-7 351.401 C14H13N3O4S2 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Meloxicam is an anti-inflammatory, analgesic analgesic with antipyretic effects in fever.1 Prostaglandins are substances that contribute to inflammation.7 This drug also exerts preferential actions against COX-23, which may reduce the possible gastrointestinal effects of this drug. D0G7FJ DB00816 Orciprenaline small molecule approved 586-06-1 211.2576 C11H17NO3 P07550#Beta-2 adrenergic receptor Orciprenaline (also known as metaproterenol), a synthetic amine, is structurally and pharmacologically similar to isoproterenol. Orciprenaline is used exclusively as a bronchodilator. The pharmacological effects of beta adrenergic agonist drugs, such as orciprenaline, are at least in part attributable to stimulation through beta adrenergic receptors of intracellular adenyl cyclase, the enzyme which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic- 3',5'- adenosine monophosphate (c-AMP). Increased cAMP levels lead to relaxation of bronchial smooth muscles and inhibition of the release of inalammatory mediators from mast cells that are involved in promoting immediate hypersensitivity . DB00817 Rosoxacin small molecule approved 40034-42-2 294.3047 C17H14N2O3 P0AFI2#DNA topoisomerase 4 subunit A@P0AES6#DNA gyrase subunit B Rosoxacin is a nonfluorinated quinolone antibiotic. Its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Rosoxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. D07CPU DB08439 Parecoxib small molecule approved 198470-84-7 370.422 C19H18N2O4S P35354#Prostaglandin G/H synthase 2@P02788#Lactotransferrin Not Available D05UWI DB08604 Triclosan small molecule approved 3380-34-5 289.542 C12H7Cl3O2 P10275#Androgen receptor@P37231#Peroxisome proliferator-activated receptor gamma@P9WGR1#Enoyl-[acyl-carrier-protein] reductase [NADH]@O75469#Nuclear receptor subfamily 1 group I member 2@O24990#Enoyl-[acyl-carrier-protein] reductase [NADH] FabI@P0AEK4#Enoyl-[acyl-carrier-protein] reductase [NADH] FabI@Q14994#Nuclear receptor subfamily 1 group I member 3@Q6GI75#Enoyl-[acyl-carrier-protein] reductase [NADPH] FabI@A0A6L8PBX8#Enoyl-[acyl-carrier-protein] reductase [NADH] Not Available D00CSQ DB08797 Salicylamide small molecule approved 65-45-2 137.136 C7H7NO2 Not Available D07MCK DB08799 Antazoline small molecule approved 91-75-8 265.3529 C17H19N3 P70174#Histamine H1 receptor Antazoline is a histamine H1 receptor antagonist. It selectively bind to but does not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. D06FZX DB08801 Dimetindene small molecule approved 5636-83-9 292.418 C20H24N2 P70174#Histamine H1 receptor@P08172#Muscarinic acetylcholine receptor M2 Dimethindene occurs as a racemic mixture. The (S)-(+)-dimethindene is a potent M2-selective muscarinic receptor antagonist (with lower affinity for M1, M3, and M4 muscarinic receptors). The (R)-(-)-enantiomer is the eutomer (responsible for bioactivity) for histamine H1 receptor binding. DB08804 Nandrolone decanoate small molecule approved 360-70-3 428.6472 C28H44O3 P10275#Androgen receptor@P28222#5-hydroxytryptamine receptor 1B@P08069#Insulin-like growth factor 1 receptor@P01100#Proto-oncogene c-Fos@P41595#5-hydroxytryptamine receptor 2B@P21728#D(1A) dopamine receptor@P14416#D(2) dopamine receptor@P35462#D(3) dopamine receptor Nandrolone decanoate is an alkylated anabolic steroid indicated in the management of anemia of renal insufficiency and as an adjunct therapy in the treatment of senile and postmenopausal osteoporosis.8,12,13 It has a long duration of action as it is given every 3-4 weeks, and a wide therapeutic window as acute overdoses are rare.8,13 Patients should be counselled regarding the risks of giving this drug to patients with cardiac, renal, or hepatic diseases.13 DB08809 Dichloroacetic acid small molecule approved 79-43-6 128.942 C2H2Cl2O2 O43708#Maleylacetoacetate isomerase@Q15118#[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Not Available DB08814 Triflusal small molecule approved 322-79-2 248.157 C10H7F3O4 P23219#Prostaglandin G/H synthase 1@P19838#Nuclear factor NF-kappa-B p105 subunit@P35228#Nitric oxide synthase, inducible@Q9Y233#cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Triflusal is an antithrombotic anticoagulant. It irreversibly inhibits the production of thromboxane-B2 in platelets by acetylating cycloxygenase-1. Triflusal affects many other targets such as NF kappa B, which is a gene expression regulatory factor for cycloxygenase-a and cytokines. Numerous studies comparing the efficacy and safety profile (i.e. systemic hemorrhage) between triflusal and acetylsalsylic acid has shown either no significant difference or a better effacy and safety profile for triflusal. Triflusal has been shown to protect cerebral tissue due to its inhibition of lipid peroxidation resulting from anoxia-reoxygenation.1 DB08815 Lurasidone small molecule approved 367514-87-2 492.676 C28H36N4O2S P28223#5-hydroxytryptamine receptor 2A@P34969#5-hydroxytryptamine receptor 7@P08908#5-hydroxytryptamine receptor 1A@P18825#Alpha-2C adrenergic receptor@P08913#Alpha-2A adrenergic receptor Lurasidone is a benzothiazol derivative that is an antagonist and binds with high affinity to Dopamine-2 (D2) (Ki = 0.994 nM), 5-HT2A (Ki = 0.47 nM) receptors, and 5-HT7 receptors (Ki = 0.495 nM). It also binds with moderate affinity to alpha-2C adrenergic receptors (Ki = 10.8 nM) and is a partial agonist at 5-HT1A receptors (Ki = 6.38 nM). Its actions on histaminergic and muscarinic receptors are negligible. DB08816 Ticagrelor small molecule approved 274693-27-5 522.568 C23H28F2N6O4S Q9H244#P2Y purinoceptor 12 Ticagrelor is a P2Y12 receptor antagonist that inhibits the formation of thromboses to reduce the risk of myocardial infarction and ischemic stroke.1,3 It has a moderate duration of action as it is given twice daily, and a wide therapeutic index as high single doses are well tolerated.6,7 Patients should be counselled regarding the risk of bleeding, dyspnea, and bradyarrhythmias.6 DB08818 Hyaluronic acid small molecule approved 9004-61-9 776.6486 C28H44N2O23 P05362#Intercellular adhesion molecule 1@P16070#CD44 antigen@Q07021#Complement component 1 Q subcomponent-binding protein, mitochondrial@P98066#Tumor necrosis factor-inducible gene 6 protein HA has long-acting lubricant, shock absorbing, joint stabilizing, and water balancing properties.2,17 It is similar to the naturally occurring glycosaminoglycan (GAG) in joints. Hyaluronic acid works by acting as a lubricant and shock absorber, facilitating joint mobility and thereby reducing osteoarthritic pain. Hyaluronic acid has antioxidative, anti-inflammatory, and analgesic effects.2 The water-balancing properties and viscoelasticity of hyaluronic acid are beneficial in cosmetic injections, imparting volume and reducing the appearance of imperfections and wrinkles.17 Due to the abovementioned properties, HA has a protective effect on the eyes and cornea.3 DB08819 Tafluprost small molecule approved 209860-87-7 452.5313 C25H34F2O5 P43088#Prostaglandin F2-alpha receptor Tafluprost is a novel prostaglandin analog with a high affinity for the fluoroprostaglandin (FP) receptor PGF2α. Tafluprost has an affinity for the FP receptor that is approximately 12 times higher than that of the carboxylic acid of latanoprost, but with almost no potential to bind to other receptors. D04LCQ DB08820 Ivacaftor small molecule approved 873054-44-5 392.4907 C24H28N2O3 P13569#Cystic fibrosis transmembrane conductance regulator The use of Ivacaftor has been shown to both improve CF symptoms and modulate underlying disease pathology. This is achieved by potentiating the channel opening probability (or gating) of CFTR protein in patients with impaired gating mechanisms. This is in contrast to Lumacaftor, another CF medication, that functions by preventing misfolding of the CFTR protein and thereby results in increased processing and trafficking of mature protein to the cell surface. D0W7WC DB08822 Azilsartan medoxomil small molecule approved 863031-21-4 568.5336 C30H24N4O8 P30556#Type-1 angiotensin II receptor Pharmacodynamic effects of azilsartan medoxomil are mediated by its active metabolite, azilsartan. Azilsartan inhibits the pressor effects of an angiotensin II infusion in a dose-related manner.1 At a single 32 mg dose, azilsartan inhibited the maximal pressor effect by approximately 90% at peak plasma concentrations and by 60% at 24 hours after administration. In healthy subjects receiving single and repeated doses of azilsartan medoxomil, plasma angiotensin I and II concentrations and plasma renin activity increased, while plasma aldosterone concentrations decreased.6 Like other ARBs, azilsartan causes dose-dependent decrease in peripheral resistance and decreases smooth muscle vascular tone.4 As azilsartan blocks the angiotensin II receptor, the negative regulatory feedback of angiotensin II on renin secretion is inhibited; however, the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the blood pressure-lowering effect of azilsartan. Blood pressure-lowering effects of antihypertensive agents can be reduced in patients of African descent.6 However, there are no recommended dosage adjustment of azilsartan on the basis of a patient’s sex, race, or degree of renal or hepatic impairment.5 DB08823 Spinosad small molecule approved 168316-95-8 1477.963 C83H132N2O20 Spinosyn A does not appear to directly interact with any known relevant insecticidal targets, but instead boasts a novel mechanism that resembles a GABA antagonist. Spinosyn A is also slightly more biologically active than spinosyn D. D09WCM DB08824 Ioflupane I-123 small molecule approved 155798-07-5 427.291 C18H23FINO2 iodine-123 labeled ioflupanebinds selectively to striatal presynaptic dopamine neurons by binding reversibly to presynaptic dopamine transporters. DB08826 Deferiprone small molecule approved 30652-11-0 139.1519 C7H9NO2 Not Available D0N0OU DB08827 Lomitapide small molecule approved 182431-12-5 693.7204 C39H37F6N3O2 P55157#Microsomal triglyceride transfer protein large subunit Lomitapide directly inhibits microsomal triglyceride transfer protein (MTP). DB08828 Vismodegib small molecule approved 879085-55-9 421.297 C19H14Cl2N2O3S Q99835#Smoothened homolog Vismodegib selectively binds to and inhibits the transmembrane protein Smoothened homologue (SMO) to inhibit the Hedgehog signalling pathway. D03EDQ DB08842 Acetylcarnitine small molecule approved 3040-38-8 203.238 C9H17NO4 The complete physiological effects of acetycarnitine are still being studied. What has been discovered so far is that acetylcarinitine has positive effects on mental fatigue, neurodegenerative disorders, cognitive functions, peripheral neuropathy, and sperm motility. Specifically, in one study involving patients with HIV, patients on acetylcarnitine supplementation had increased CD4 cells, decreased lymphocyte apoptosis, improved polyneuropathy and cardiovascular damage, and decreased triglyceride and TNF alpha levels in the blood. Another study showed that acetylcarnitine increased glucose disposal in type 2 diabetic patients through possibly increasing the activity of glycogen synthase. DB08860 Pitavastatin small molecule approved 147511-69-1 421.4608 C25H24FNO4 P04035#3-hydroxy-3-methylglutaryl-coenzyme A reductase@P20701#Integrin alpha-L Pitavastatin is an oral antilipemic agent which inhibits HMG-CoA reductase. It is used to lower total cholesterol, low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (apoB), non-high density lipoprotein-cholesterol (non-HDL-C), and trigleride (TG) plasma concentrations while increasing HDL-C concentrations. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, rosuvastatin reduces the risk of cardiovascular morbidity and mortality.4,5 DB08864 Rilpivirine small molecule approved 500287-72-9 366.4185 C22H18N6 Q72547#Reverse transcriptase/RNaseH@O75469#Nuclear receptor subfamily 1 group I member 2 Rilpivirine is a non-nucleoside reverse transcriptase inhibitor that inhibits the replication of HIV-1.9 It has a long duration of action as the oral tablet is given daily and the intramuscular suspension is given monthly.9,10 Patients should be counselled regarding the risk of hypersensitivity reactions, hepatotoxicity, depressive disorders, and the redistribution or accumulation of body fat.9 D0T6WN DB08865 Crizotinib small molecule approved 877399-52-5 450.337 C21H22Cl2FN5O Q9UM73#ALK tyrosine kinase receptor@P08581#Hepatocyte growth factor receptor Not Available D03ZBT DB08867 Ulipristal small molecule approved 159811-51-5 433.592 C28H35NO3 P06401#Progesterone receptor@P04150#Glucocorticoid receptor@P10275#Androgen receptor Ulipristal is a selective, reversible progestin receptor modulator and its tissue targets include the uterus, cervix, ovaries, and hypothalamus. Ulipristal may act as an agonist or antagonist in the presence or absence of progesterone based on the tissue target. If given mid-follicular phase, development of the follicle growth is delayed and estradiol concentrations decrease. If given at the time when luteinizing hormone peaks, follicular rapture is delayed by several days. If given early-luteal phase, a decrease in endometrial thickness can be observed. D0V4WD DB08868 Fingolimod small molecule approved 162359-55-9 307.4708 C19H33NO2 Q9H228#Sphingosine 1-phosphate receptor 5@P21453#Sphingosine 1-phosphate receptor 1@Q99500#Sphingosine 1-phosphate receptor 3@Q13547#Histone deacetylase 1@O95977#Sphingosine 1-phosphate receptor 4 In multiple sclerosis, fingolimod binds to sphingosine receptors, reducing its associated neuroinflammation.12In COVID-19, it may reduce lung inflammation and improve the clinical outcomes of patients with this disease.13 D07UHS DB08869 Tesamorelin small molecule approved 218949-48-5 5005.76 C216H360N72O63S Q02643#Growth hormone-releasing hormone receptor Tesamorelin stimulates growth hormone secretion, and subsequently increases IGF-1 and IGFBP-3 levels. D0UL9R DB08871 Eribulin small molecule approved 253128-41-5 729.908 C40H59NO11 P10415#Apoptosis regulator Bcl-2@Q9H4B7#Tubulin beta-1 chain Linear D0KK2E DB08872 Gabapentin enacarbil small molecule approved 478296-72-9 329.393 C16H27NO6 P54289#Voltage-dependent calcium channel subunit alpha-2/delta-1@Q9NY47#Voltage-dependent calcium channel subunit alpha-2/delta-2 Since gabapentin enacarbil is a prodrug of gabapentin, it's physiological effects are the same as gabapentin. Concerning PHN, gabapentin prevents allodynia and hyperalgesia. D05KBU DB08873 Boceprevir small molecule approved 394730-60-0 519.6767 C27H45N5O5 Boceprevir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1 Label. DB08874 Fidaxomicin small molecule approved 873857-62-6 1058.05 C52H74Cl2O18 Fidaxomicin has a narrow-spectrum antibacterial profile, with potent bactericidal activity specifically against C. difficile.5 The minimum inhibitory concentration for 90% of organisms for fidaxomicin against C. difficile ranged from 0.0078 to 2 μg/mL in vitro.2 The bactericidal activity of fidaxomicin is time-dependent.6 Other than C. difficile, fidaxomicin has moderate inhibitory activity against Gram-positive bacteria (S. aureus and Enterococcus spp.) 5 and poor activity against normal colonic flora, including anaerobes and enteric Gram-negative bacilli.4 Isolates of C. difficile that are resistant to rifamycins or other antimicrobial classes (such as cephalosporins, fluoroquinolones, clindamycin) were not shown to be cross-resistant to fidaxomicin.4 D06LNW DB08875 Cabozantinib small molecule approved 849217-68-1 501.514 C28H24FN3O5 P08581#Hepatocyte growth factor receptor@P35968#Vascular endothelial growth factor receptor 2@P07949#Proto-oncogene tyrosine-protein kinase receptor Ret Cabozantinib suppresses metastasis, angiogenesis, and oncognesis by inhibiting receptor tyrosine kinases. D0IQ6P DB08877 Ruxolitinib small molecule approved 941678-49-5 306.365 C17H18N6 O60674#Tyrosine-protein kinase JAK2@P23458#Tyrosine-protein kinase JAK1@P52333#Tyrosine-protein kinase JAK3@P29597#Non-receptor tyrosine-protein kinase TYK2 Ruxolitinib is an antineoplastic agent that inhibits cell proliferation, induces apoptosis of malignant cells, and reduces pro-inflammatory cytokine plasma levels by inhibiting JAK-induced phosphorylation of signal transducer and activator of transcription (STAT).4 Inhibition of STAT3 phosphorylation, which is used as a marker of JAK activity, 2 by ruxolitinib is achieved at two hours after dosing which returned to near baseline by 10 hours in patients with myelofibrosis and polycythemia vera.16 In clinical trials, ruxolitinib reduced splenomegaly and improved symptoms of myelofibrosis.4 In a mouse model of myeloproliferative neoplasms, administration of ruxolitinib was associated with prolonged survival.2 Ruxolitinib inhibits both mutant and wild-type JAK2 4; however, JAK2V617F mutation, which is often seen in approximately 50% of patients with myelofibrosis, was shown to reduce ruxolitinib sensitivity, which may also be associated with possible resistance to JAK inhibitor treatment.14 D04LKS DB08880 Teriflunomide small molecule approved 163451-81-8 270.2073 C12H9F3N2O2 Q02127#Dihydroorotate dehydrogenase (quinone), mitochondrial D07QFP DB08881 Vemurafenib small molecule approved 918504-65-1 489.922 C23H18ClF2N3O3S P15056#Serine/threonine-protein kinase B-raf BRAF activation results in cell growth, proliferation, and metastasis. BRAF is an intermediary molecule in MAPK whose activation depends on ERK activation, elevation of cyclin D1 and cellular proliferation. The mutation V600E produces a constitutively form of BRAF. Vemurafenib has been shown to reduce all activation markers related to BRAF; in clinical trials, vemurafenib treatment showed a reduction of cytoplasmic phosphorylated ERK and a cell proliferation driven by Ki-67. Studies also reported decrease in MAPK-related metabolic activity.3 All the different reports indicate thet Vemurafenib generates an almost complete inhibition of the MAPK pathway. D0Y9EW DB08882 Linagliptin small molecule approved 668270-12-0 472.5422 C25H28N8O2 P27487#Dipeptidyl peptidase 4 A 5mg oral dose of linagliptin results in >80% inhibition of dipeptidyl peptidase 4 (DPP-4) for ≥24 hours3. Inhibition of DPP-4 increases the concentration of glucagon-like peptide 1 (GLP-1), leading to decreased glycosylated hemoglobin and fasting plasma glucose3. D02EYG DB08883 Perampanel small molecule approved 380917-97-5 349.393 C23H15N3O DB08884 Gadoxetic acid small molecule approved 135326-11-3 681.75 C23H30GdN3O11 Gadoxetate disodium is an amphipathic compound in which gadoxetate is hydrophillic and its moiety, the ethoxybenyzl group, is lipophillic. Consequently, gadoxetate disodium has a biphasic mode of action in which it first distributes into the extracellular space after bolus injection and then hepatocytes selectively takes up the drug. DB08887 Icosapent ethyl small molecule approved 86227-47-6 330.5042 C22H34O2 Not Available DB08889 Carfilzomib small molecule approved 868540-17-4 719.9099 C40H57N5O7 P28074#Proteasome subunit beta type-5@P28062#Proteasome subunit beta type-8@P20618#Proteasome subunit beta type-1@P28065#Proteasome subunit beta type-9@P49721#Proteasome subunit beta type-2@P40306#Proteasome subunit beta type-10 Intravenous carfilzomib administration resulted in suppression of proteasome chymotrypsin-like activity when measured in blood 1 hour after the first dose. On Day 1 of Cycle 1, proteasome inhibition in peripheral blood mononuclear cells (PBMCs) ranged from 79% to 89% at 15 mg/m2, and from 82% to 83% at 20 mg/m2. In addition, carfilzomib administration resulted in inhibition of the LMP2 and MECL1 subunits of the immunoproteasome ranging from 26% to 32% and 41% to 49%, respectively, at 20 mg/m2. Proteasome inhibition was maintained for ≥ 48 hours following the first dose of carfilzomib for each week of dosing. Resistance against carfilzomib has been observed and although the mechanism has not been confirmed, it is thought that up-regulation of P-glycoprotein may be a contributing factor. Furthermore, studies suggest that carfilzomib is more potent than bortezomib. D00UVA DB08890 Linaclotide small molecule approved 851199-59-2 1526.736 C59H79N15O21S6 P25092#Heat-stable enterotoxin receptor Changes in the appearance and consistency of stools as measured by the Bristol Stool Form Scale (BSFS) have been noted after taking linaclotide. D00GNJ DB08893 Mirabegron small molecule approved 223673-61-8 396.506 C21H24N4O2S P13945#Beta-3 adrenergic receptor@P08588#Beta-1 adrenergic receptor Mirabegron exerts its pharmacologic effects by forcing bladder smooth muscle to relax, thereby expanding its capacity and relieving urgency. Mirabegron does not appear to adversely affect the mean maximum flow rate or mean detrusor pressure at maximum flow rate in patients with lower urinary tract symptoms and bladder outlet obstruction (BOO), but should be used with in patients with BOO due to reports of significant urinary retention. Furthermore, mirabegron increases both blood pressure and heart rate in a dose-dependent manner and should therefore be used with caution in patients with severely uncontrolled hypertension or others for whom these increases may prove dangerous.6 D0X5UN DB08895 Tofacitinib small molecule approved 477600-75-2 312.3696 C16H20N6O P23458#Tyrosine-protein kinase JAK1@O60674#Tyrosine-protein kinase JAK2@P52333#Tyrosine-protein kinase JAK3@P29597#Non-receptor tyrosine-protein kinase TYK2 Tofacitinib targets inflammation present in rheumatoid arthritis by inhibiting the janus kinases involved in the inflammatory response pathway. D0EG1I DB08896 Regorafenib small molecule approved 755037-03-7 482.815 C21H15ClF4N4O3 P00519#Tyrosine-protein kinase ABL1@P35916#Vascular endothelial growth factor receptor 3@P17948#Vascular endothelial growth factor receptor 1@P04049#RAF proto-oncogene serine/threonine-protein kinase@P09619#Platelet-derived growth factor receptor beta@P35968#Vascular endothelial growth factor receptor 2@P10721#Mast/stem cell growth factor receptor Kit@P15056#Serine/threonine-protein kinase B-raf@P21802#Fibroblast growth factor receptor 2@P29317#Ephrin type-A receptor 2@P16234#Platelet-derived growth factor receptor alpha@P04629#High affinity nerve growth factor receptor@P11362#Fibroblast growth factor receptor 1@P07949#Proto-oncogene tyrosine-protein kinase receptor Ret@Q02763#Angiopoietin-1 receptor@Q15759#Mitogen-activated protein kinase 11@Q16832#Discoidin domain-containing receptor 2 Not Available D09GDD DB08897 Aclidinium small molecule approved 727649-81-2 484.651 C26H30NO4S2 P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5 Aclidinium does not prolong the QTc interval or have significant effects on cardiac rhythm. D0VP1V DB08899 Enzalutamide small molecule approved 915087-33-1 464.436 C21H16F4N4O2S P10275#Androgen receptor Resitance to enzalutamide therapy has been observed. This may occurred due to an upregulation of NF-κB2/p52. D0QK5X DB08901 Ponatinib small molecule approved 943319-70-8 532.5595 C29H27F3N6O P00519#Tyrosine-protein kinase ABL1@P11274#Breakpoint cluster region protein Not Available D0H0EQ DB08903 Bedaquiline small molecule approved 843663-66-1 555.505 C32H31BrN2O2 P9WPS1#ATP synthase subunit c Bedaquiline is primarily subjected to oxidative metabolism leading to the formation of N-monodesmethyl metabolite (M2). M2 is not thought to contribute significantly to clinical efficacy given its lower average exposure (23% to 31%) in humans and lower antimycobacterial activity (4 to 6-fold lower) compared to the parent compound. M2 concentrations appeared to correlate with QT prolongation. Bedaquiline inhibits mycobacterial TB at a minimal inhibitory concentration (MIC) from 0.002-0.06 μg/ml and with a MIC50 of 0.03 μg/ml. Furthermore, bacteria that have smaller ATP stores (usually in dormant, nonreplicating bacilli) are more susceptible to bedaquiline. D0Y4QG DB08905 Formestane small molecule approved 566-48-3 302.4079 C19H26O3 By significantly reducing estrogen levels in the bloodstream, formestane may exhibit antitumor activity. DB08906 Fluticasone furoate small molecule approved 397864-44-7 538.576 C27H29F3O6S P04150#Glucocorticoid receptor@P06401#Progesterone receptor@P08235#Mineralocorticoid receptor Systemically, in vitro experiments show fluticasone furoate activates glucocorticoid receptors, inhibits nuclear factor kappa b, and inhibits lung eosinophilia in ratsLabel12,4. DB08907 Canagliflozin small molecule approved 842133-18-0 444.516 C24H25FO5S P31639#Sodium/glucose cotransporter 2 This drug increases urinary glucose excretion and decreases the renal threshold for glucose (RTG) in a dose-dependent manner Label. The renal threshold is defined as the lowest level of blood glucose associated with the appearance of detectable glucose in the urine 2,7. The end result of canagliflozin administration is increased urinary excretion of glucose and less renal absorption of glucose, decreasing glucose concentration in the blood and improving glycemic control. D08DFX DB08908 Dimethyl fumarate small molecule approved 624-49-7 144.1253 C6H8O4 Q14145#Kelch-like ECH-associated protein 1@Q04206#Transcription factor p65 The physiological effects dimethyl fumarate has on the body is not well understood. It is known that dimethyl fumarate has anti-inflammatory and cytoprotective effects, which both are likely involved in its actions in multiple sclerosis patients. DB08909 Glycerol phenylbutyrate small molecule approved 611168-24-2 530.6512 C33H38O6 Glycerol phenylbutyrate prolongs the QTc interval. D0E0BD DB08910 Pomalidomide small molecule approved 19171-19-8 273.2441 C13H11N3O4 Q96SW2#Protein cereblon@P01375#Tumor necrosis factor@P35354#Prostaglandin G/H synthase 2 Pomalidomide is more potent than thalidomide (100-times) and lenalidomide (10-times). D0A3ZU DB08911 Trametinib small molecule approved 871700-17-3 615.3948 C26H23FIN5O4 Q02750#Dual specificity mitogen-activated protein kinase kinase 1@P36507#Dual specificity mitogen-activated protein kinase kinase 2 Trametinib is an anticancer agent which causes apoptosis (or programmed cell death) and inhibits cell proliferation, which are both important in the treatment of malignancies 2. D04XVN DB08912 Dabrafenib small molecule approved 1195765-45-7 519.562 C23H20F3N5O2S2 P15056#Serine/threonine-protein kinase B-raf@P04049#RAF proto-oncogene serine/threonine-protein kinase@P57059#Serine/threonine-protein kinase SIK1@Q8NG66#Serine/threonine-protein kinase Nek11@P53667#LIM domain kinase 1 Dabrafenib is a kinase inhibitor that is mainly used to target BRAF V600E mutation in multiple types of cancer. Although dabrafenib and trametinib both inhibit the RAS/RAF/MEK/ERK pathway, they inhibit different effectors of the pathway, thus increasing response rate and mitigating resistance without cumulative toxicity.11 D05ROI DB08913 Radium Ra 223 dichloride small molecule approved 444811-40-9 293.924 Cl2Ra Physiologically, Radium Ra 223 Dichloride, prevents the spread of bone cancer by killing the associated bone cancer cells. DB08916 Afatinib small molecule approved 850140-72-6 485.938 C24H25ClFN5O3 P00533#Epidermal growth factor receptor@P04626#Receptor tyrosine-protein kinase erbB-2@Q15303#Receptor tyrosine-protein kinase erbB-4 Aberrant ErbB signaling triggered by receptor mutations, and/or amplification, and/or receptor ligand overexpression contributes to the malignant phenotype 3. Mutation in EGFR defines a distinct molecular subtype of lung cancer 3. DB08918 Levomilnacipran small molecule approved 96847-54-0 246.348 C15H22N2O P31645#Sodium-dependent serotonin transporter@P23975#Sodium-dependent noradrenaline transporter Levomilnacipran binds with high affinity to human serotonin (5-HT) and norepinephrine (NE) transporters (Ki = 11 and 91 nM, respectively). It potently inhibits 5-HT and NE reuptake (IC50 = 16 - 19 and 11 nM, respectively). Levomilnacipran does not bind to any other receptors, ion channels, or transporters, including serotonergic (5HT1-7), α- and β adrenergic, muscarinic, or histaminergic receptors and Ca2+, Na+, K+ or Cl- channels to a significant degree. Levomilnacipran did not inhibit monoamine oxidase (MAO). Furthermore, levomilnacipran does not prolong the QTc interval to a clinically relevant extent. D02XOK DB08930 Dolutegravir small molecule approved 1051375-16-6 419.3788 C20H19F2N3O5 D00YZD DB08931 Riociguat small molecule approved 625115-55-1 422.4157 C20H19FN8O2 D04UKC DB08932 Macitentan small molecule approved 441798-33-0 588.273 C19H20Br2N6O4S P25101#Endothelin-1 receptor@P24530#Endothelin B receptor Macitentan acts primarily by reducing vasoconstriction and cell proliferation due to endothelin overexpression.5,6 D0S7JH DB08933 Luliconazole small molecule approved 187164-19-8 354.27 C14H9Cl2N3S2 Luliconazole kills the organisms Trichophyton rubrum and Epidermophyton floccosum, most likely by altering their fungal cell membranes. D0U4XJ DB08934 Sofosbuvir small molecule approved 1190307-88-0 529.458 C22H29FN3O9P O39930#RNA-dependent RNA-polymerase Sofosbuvir acts against HCV and is categorized as a direct-acting antiviral agent (DAA). DB08936 Chlorcyclizine small molecule approved 82-93-9 300.826 C18H21ClN2 P70174#Histamine H1 receptor Not Available DB08938 Magaldrate small molecule approved 74978-16-8 1115.3 Al5H33Mg10O40S2 Not Available DB08941 Isoxsuprine small molecule approved 395-28-8 301.386 C18H23NO3 Not Available D0O8OB DB08942 Isoxicam small molecule approved 34552-84-6 335.335 C14H13N3O5S Not Available D03JPH DB08943 Isoconazole small molecule approved 27523-40-6 416.129 C18H14Cl4N2O Not Available DB08944 Isoaminile small molecule approved 77-51-0 244.382 C16H24N2 Not Available DB08946 Iopanoic acid small molecule approved 96-83-3 570.9319 C11H12I3NO2 Not Available D0A5JP DB08947 Iopamidol small molecule approved 60166-93-0 777.0853 C17H22I3N3O8 Not Available D0O2HQ DB08949 Inositol nicotinate small molecule approved 6556-11-2 810.732 C42H30N6O12 P49019#Hydroxycarboxylic acid receptor 3@Q8TDS4#Hydroxycarboxylic acid receptor 2 Inositol nicotinate mediates a vasodilatory, lipid-lowering and fibrinolytic effect on the cardiovascular system. Like other niacins, inositol nicotinate is a lipid-regulating agent that reduces the levels of plasma triglycerides, atherogenic apolipoprotein B (apoB)-containing lipoproteins (VLDL, LDL and lipoprotein a) while increasing antiatherogenic apoA-I-containing HDL levels 10. DB08950 Indoramin small molecule approved 26844-12-2 347.4534 C22H25N3O P35348#Alpha-1A adrenergic receptor Not Available DB08954 Ifenprodil small molecule approved 23210-56-2 325.4446 C21H27NO2 Q13224#Glutamate receptor ionotropic, NMDA 2B@Q05586#Glutamate receptor ionotropic, NMDA 1@P48549#G protein-activated inward rectifier potassium channel 1@P48051#G protein-activated inward rectifier potassium channel 2@P48544#G protein-activated inward rectifier potassium channel 4 Not Available DB08958 Hexetidine small molecule approved 141-94-6 339.6021 C21H45N3 Not Available DB08964 Gemeprost small molecule approved 64318-79-2 394.552 C23H38O5 P43115#Prostaglandin E2 receptor EP3 subtype@P43116#Prostaglandin E2 receptor EP2 subtype Gemeprost softens and dilates of the cervix prior to transcervical intrauterine operative procedures. It is a prostaglandin E1 analog that potently stimulates uterine contractions and causes cervical ripening and relaxation 1. D0EC5X DB08965 Fusafungine small molecule approved 1393-87-9 639.8204 C33H57N3O9 Not Available D07KDE DB08966 Fursultiamine small molecule approved 804-30-8 398.543 C17H26N4O3S2 Not Available DB08967 Dimetotiazine small molecule approved 7456-24-8 391.55 C19H25N3O2S2 Not Available DB08971 Fluocortolone small molecule approved 152-97-6 376.4617 C22H29FO4 Not Available DB08973 Fluclorolone acetonide small molecule approved 3693-39-8 487.39 C24H29Cl2FO5 Not Available DB08976 Floctafenine small molecule approved 23779-99-9 406.3552 C20H17F3N2O4 Not Available D0AK5R DB08981 Fenbufen small molecule approved 36330-85-5 254.2806 C16H14O3 Not Available DB08987 Etidocaine small molecule approved 36637-18-0 276.417 C17H28N2O Not Available D0G7DJ DB08988 Ethoheptazine small molecule approved 77-15-6 261.3593 C16H23NO2 Not Available DB08995 Diosmin small molecule approved 520-27-4 608.5447 C28H32O15 P35869#Aryl hydrocarbon receptor Diosmin is a venoactive drug supporting circulatory health through various actions on blood vessels; it supports lymphatic drainage and improves microcirculation while increasing venous tone and elasticity. For these reasons, diosmin is frequently taken by individuals with chronic venous disease to support vascular health and has been demonstrated to improve quality of life.3,17 In addition to the above effects, diosmin exerts antioxidant activity and scavenges oxygen free radicals, reducing levels of oxidative stress normally detected through biomarkers such as prostaglandins isoprostane precursors.1 D0X9XP DB09009 Articaine small molecule approved 23964-58-1 284.374 C13H20N2O3S Not Available D0I5HV DB09015 Canrenoic acid small molecule approved 4138-96-9 358.478 C22H30O4 Not Available DB09019 Bromhexine small molecule approved 3572-43-8 376.13 C14H20Br2N2 O15393#Transmembrane protease serine 2@Q9BYF1#Angiotensin-converting enzyme 2 Bromhexine thins airway secretions, improving breathing and discomfort associated with thick mucus in airways associated with a variety of respiratory conditions.1,11,13 D07UWJ DB09020 Bisacodyl small molecule approved 603-50-9 361.3906 C22H19NO4 Q92482#Aquaporin-3 Patients should be counselled regarding abdominal pain, nausea, vomiting, or a change in bowel function that lasts longer than 2 weeks.9 It has a wide therapeutic index, as patients can take 5-15 mg orally.9 Patients taking bisacodyl should be counselled before taking the medication if they are already experiencing abdominal pain, nausea, vomiting, or a change in bowel function lasting longer than 2 weeks.9 Patients should also be counselled to stop taking the medication if they experience rectal bleeding or no bowel movement in 12 hours.9 D07IEF DB09026 Aliskiren small molecule approved 173334-57-1 551.7583 C30H53N3O6 P00797#Renin Aliskiren reduces blood pressure by inhibiting renin. This leads to a cascade of events that decreases blood pressure, lowering the risk of fatal and nonfatal cardiovascular events including stroke and myocardial infarction.2,9 D03SVX DB09027 Ledipasvir small molecule approved 1256388-51-8 888.9999 C49H54F2N8O6 Q5L478#Nonstructural protein 5A Ledipasvir acts against HCV and is categorized as a direct-acting antiviral agent (DAA). DB09030 Vorapaxar small molecule approved 618385-01-6 492.5817 C29H33FN2O4 P25116#Proteinase-activated receptor 1 Not Available D0VA0I DB09031 Miltefosine small molecule approved 58066-85-6 407.576 C21H46NO4P Little is known about the clinical pharmacodynamics of miltefosine and other antileishmanial drugs. D00FGR DB09034 Suvorexant small molecule approved 1030377-33-3 450.93 C23H23ClN6O2 O43613#Orexin receptor type 1@O43614#Orexin receptor type 2 Not Available D00OVU DB09038 Empagliflozin small molecule approved 864070-44-0 450.91 C23H27ClO7 P31639#Sodium/glucose cotransporter 2 Empagliflozin lowers blood glucose levels by preventing glucose reabsorption in the kidneys, thereby increasing the amount of glucose excreted in the urine.18 It has a relatively long duration of action requiring only once-daily dosing. Patients should be monitored closely for signs and symptoms of ketoacidosis regardless of blood glucose level as empagliflozin may precipitate diabetic ketoacidosis in the absence of hyperglycemia.18 As its mechanism of action is contingent on the renal excretion of glucose, empagliflozin may be held in cases of acute kidney injury and/or discontinued in patients who develop chronic renal disease. D06ALD DB09039 Eliglustat small molecule approved 491833-29-5 404.551 C23H36N2O4 Q16739#Ceramide glucosyltransferase Eliglustat is a specific inhibitor of glucosylceramide synthase (IC50 =10 ng/mL).6 In vitro studies suggest that eliglustat has minimal or no off-target activity against other glycosidases, such as α-glucosidase I and II, and lysosomal and non-lysosomal glucosylceramidases.3 DB09040 Efinaconazole small molecule approved 164650-44-6 348.398 C18H22F2N4O Q16850#Lanosterol 14-alpha demethylase mean ± SD plasma Cmax on Day 28 of treatment: 0.67 ± 0.37 ng/mL. D0G4BI DB09041 Tavaborole small molecule approved 174671-46-6 151.93 C7H6BFO2 D05VGL DB09042 Tedizolid phosphate small molecule approved 856867-55-5 450.323 C17H16FN6O6P DB09047 Finafloxacin small molecule approved 209342-40-5 398.394 C20H19FN4O4 P11388#DNA topoisomerase 2-alpha D01IXD DB09048 Netupitant small molecule approved 290297-26-6 578.603 C30H32F6N4O P25103#Substance-P receptor Not Available D0G3YC DB09049 Naloxegol small molecule approved 854601-70-0 651.794 C34H53NO11 D07LCF DB09050 Ceftolozane small molecule approved 689293-68-3 666.69 C23H30N12O8S2 Q51504#Cell division protein@P0AEB2#D-alanyl-D-alanine carboxypeptidase DacA@P24228#D-alanyl-D-alanine carboxypeptidase DacB@P08506#D-alanyl-D-alanine carboxypeptidase DacC@P02919#Penicillin-binding protein 1B Ceftolozane exerts bactericidal activities against susceptible gram-negative and gram-positive infections by interfering with bacterial cell wall synthesis.13,5 When it is combined with tazobactam, it exerts further activity against beta-lactamase enzyme producing bacteria, which are normally resistant to beta-lactam antibiotics and interfere with infection treatment.13,11 The addition of tazobactam strengthens the therapeutic response to ceftolozane, giving it the ability to treat a broader range of bacterial infections and resistant organisms.5,7,9 DB09053 Ibrutinib small molecule approved 936563-96-1 440.507 C25H24N6O2 Q06187#Tyrosine-protein kinase BTK D09KTS DB09054 Idelalisib small molecule approved 870281-82-6 415.432 C22H18FN7O O00329#Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Not Available D0J5VR DB09055 Acipimox small molecule approved 51037-30-0 154.125 C6H6N2O3 Not Available D0S1NZ DB09056 Amorolfine small molecule approved 78613-35-1 317.517 C21H35NO Not Available D0QC3M DB09059 Atosiban small molecule approved 90779-69-4 994.19 C43H67N11O12S2 P30559#Oxytocin receptor@P37288#Vasopressin V1a receptor@P47901#Vasopressin V1b receptor@P30518#Vasopressin V2 receptor Atosiban reduces the frequency of uterine contractions to delay pre-term birth in adult females and induces uterine quiescence 5,1. DB09060 Avibactam small molecule approved 1192500-31-4 265.24 C7H11N3O6S P05364#Beta-lactamase@Q939N4#Beta-lactamase@Q9L5C7#Beta-lactamase@Q840M4#Beta-lactamase@P62593#Beta-lactamase TEM@P0AD64#Beta-lactamase SHV-1@P37321#Extended-spectrum beta-lactamase PER-1@Q9F663#Carbapenem-hydrolyzing beta-lactamase KPC@Q9EXV5#Beta-lactamase UOE-1 Not Available DB09061 Cannabidiol small molecule approved 13956-29-1 314.469 C21H30O2 P21554#Cannabinoid receptor 1 D0O1UZ DB09063 Ceritinib small molecule approved 1032900-25-6 558.135 C28H36ClN5O3S Q9UM73#ALK tyrosine kinase receptor Not Available D04LVK DB09064 Ciprofibrate small molecule approved 52214-84-3 289.15 C13H14Cl2O3 Q07869#Peroxisome proliferator-activated receptor alpha Not Available D0EJ6O DB09065 Cobicistat small molecule approved 1004316-88-4 776.03 C40H53N7O5S2 Not Available D02VJP DB09067 Corticorelin ovine triflutate small molecule approved 121249-14-7 4670.38 C205H339N59O63S P34998#Corticotropin-releasing factor receptor 1 In normal subjects, intravenous administration of corticorelin results in a rapid and sustained increase of plasma ACTH levels and a near parallel increase of plasma cortisol. In addition, intravenous administration of corticorelin to normal subjects causes a concomitant and prolonged release of the related proopiomelanocortin peptides β- and γ-lipotropins (β -and γ-LPH) and β-endorphin (β -END). DB09068 Vortioxetine small molecule approved 508233-74-7 298.45 C18H22N2S P08588#Beta-1 adrenergic receptor@P28222#5-hydroxytryptamine receptor 1B D03WEX DB09069 Trimetazidine small molecule approved 5011-34-7 266.341 C14H22N2O3 P42765#3-ketoacyl-CoA thiolase, mitochondrial Trimetazidine is indicated for the symptomatic treatment of stable angina pectoris in patients inadequately controlled or intolerant to first line therapies.9 Patients should be counselled regarding the risk of use with reduced renal or hepatic function, worsening of extrapyramidal symptoms or other movement disorders, and risk of falls.10 D0Q4YI DB09070 Tibolone small molecule approved 5630-53-5 312.453 C21H28O2 P03372#Estrogen receptor Tibolone prevents bone loss and treating post-menopausal symptoms without stimulating the endometrial tissues, which may lead to malignancy. Typical, drugs that treat post-menopausal symptoms such as estrogen, have a proliferative effect on the endometrium, increasing the risk of endometrial carcinoma 8. The effects on the bone, brain and vaginal tissues can be explained by the estrogenic activity of tibolone. It is important to note that activity is not expressed in the endometrium. Tibolone behaves differently from estrogen plus progesterone combinations on the breast. Therefore, tibolone can be characterized as a selective estrogen activity regulator 1. D0W3OS DB09071 Tasimelteon small molecule approved 609799-22-6 245.322 C15H19NO2 P48039#Melatonin receptor type 1A@P49286#Melatonin receptor type 1B Not Available D0Q5MQ DB09072 Sodium oxybate small molecule approved 502-85-2 126.087 C4H7NaO3 Sodium oxybate works through an unknown mechanism to treat narcolepsy by inducing sleep within about 5-15 minutes of administration. DB09073 Palbociclib small molecule approved 571190-30-2 447.5328 C24H29N7O2 P11802#Cyclin-dependent kinase 4@Q00534#Cyclin-dependent kinase 6 Due to its mechanism of action, palbociclib inhibits cell growth and suppresses DNA replication in retinoblastoma tumor suppressor gene (RB) proficient cancer cells. As expected, these RB cells present a significant increase in the proportion of cells in G1 state and the presence of palbociclib produces effective dephosphorylation of RB, reduce proliferation and induce senescence causing cell-cycle arrest.5 D00UZR DB09074 Olaparib small molecule approved 763113-22-0 434.4628 C24H23FN4O3 P09874#Poly [ADP-ribose] polymerase 1@Q9UGN5#Poly [ADP-ribose] polymerase 2@Q9Y6F1#Poly [ADP-ribose] polymerase 3@P42330#Aldo-keto reductase family 1 member C3 Olaparib is a cytotoxic and anti-tumour agent. Olaparib inhibits the growth of selective tumour cell lines in vitro and decreases tumour growth in mouse xenograft models of human cancer, both as monotherapy or following platinum-based chemotherapy. The drug exerts anti-tumour effects in cell lines and mouse tumour models with deficiencies in BRCA1/2, ATM, or other genes involved in the homologous recombination repair (HRR) of DNA damage and correlated with platinum response.8 D0J9HW DB09075 Edoxaban small molecule approved 480449-70-5 548.06 C24H30ClN7O4S P00742#Coagulation factor X Administration of edoxaban results in prolongation of clotting time tests such as aPTT (activated partial thromboplastin time), PT (prothrombin time), and INR (international normalized ratio). DB09076 Umeclidinium small molecule approved 869185-19-3 428.595 C29H34NO2 P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P11229#Muscarinic acetylcholine receptor M1@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5 Not Available D00SLY DB09078 Lenvatinib small molecule approved 417716-92-8 426.86 C21H19ClN4O4 P35916#Vascular endothelial growth factor receptor 3@P17948#Vascular endothelial growth factor receptor 1@P35968#Vascular endothelial growth factor receptor 2@P10721#Mast/stem cell growth factor receptor Kit@P21802#Fibroblast growth factor receptor 2@P16234#Platelet-derived growth factor receptor alpha@P22455#Fibroblast growth factor receptor 4@P11362#Fibroblast growth factor receptor 1@P22607#Fibroblast growth factor receptor 3@P07949#Proto-oncogene tyrosine-protein kinase receptor Ret Based on x-ray crystallography and kinetic interaction studies, lenvatinib binds to the adenosine 5'-triphosphate binding site of VEGFR2 and to a neighbouring region via a cyclopropane ring and thereby inhibits tyrosine kinase activity and associated signalling pathways. D0R0FO DB09079 Nintedanib small molecule approved 656247-17-5 539.6248 C31H33N5O4 P35916#Vascular endothelial growth factor receptor 3@P17948#Vascular endothelial growth factor receptor 1@P09619#Platelet-derived growth factor receptor beta@P35968#Vascular endothelial growth factor receptor 2@P21802#Fibroblast growth factor receptor 2@P16234#Platelet-derived growth factor receptor alpha@P11362#Fibroblast growth factor receptor 1@P22607#Fibroblast growth factor receptor 3 Nintedanib is a small molecule kinase inhibitor that inhibits upstream kinase activity to ultimately inhibit lung fibroblast proliferation and migration, as well as signalling pathways that promote the proliferation and survival of endothelial and perivascular cells in tumour tissues.8,9,5 DB09080 Olodaterol small molecule approved 868049-49-4 386.448 C21H26N2O5 P07550#Beta-2 adrenergic receptor Olodaterol is a potent agonist of the human beta2-adrenergic receptor in vitro, and is highly selective for this receptor, with much lower levels of activity at the b1- and b3-adrenergic receptors that are commonly expressed on cardiac smooth muscle and adipose tissue, respectively. Binding to the receptor causes smooth muscle relaxation in the lungs and bronchodilation. It has also been shown to potently reverse active bronchoconstriction. D04UTT DB09081 Idebenone small molecule approved 58186-27-9 366.498 C21H34O5 Not Available D0MM8N DB09082 Vilanterol small molecule approved 503068-34-6 486.43 C24H33Cl2NO5 P07550#Beta-2 adrenergic receptor Not Available D0L0GM DB09083 Ivabradine small molecule approved 155974-00-8 468.594 C27H36N2O5 Q9UL51#Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 The funny channels (If) open during repolarization and close during depolarization, making ivabradine's activity dependent on heart rate or the closing and opening of the channels. Therefore ivabradine exhibits use-dependence and is more pharmacologically active at higher heart rates. Ivabradine exhibits a linear dose-dependent heart-rate lowering activity (bradycardic effect) until a maximum dose of 30-40mg. At higher doses, the concentration of ivabradine tends to plateau, reducing risk of serious sinus bradycardia. It has been shown that the metabolite of ivabradine lowers heart rate as well, contributing to ivabradine's overall effect. D0S9QA DB09084 Benzydamine small molecule approved 642-72-8 309.413 C19H23N3O Benzydamine is a non-steroidal anti-inflammatory drug (NSAID) designed to elicit local anesthetic and analgesic effects mainly for the mouth and throat. It specifically acts on the local mechanisms of inflammation such as pain, oedema, or granuloma. Typically applied topically, the drug demonstrates anti-inflammatory activity reducing oedema as well as exudate and granuloma formation. Moreover, benzydamine exhibits analgesic properties and local anaesthetic activity if pain is caused by an inflammatory condition. Benzydamine can be absorbed into the oral mucosa and intact skin. Once absorbed in the local area of pain or inflammation, benzydamine binds selectively to local inflamed tissues, usually allowing it to act with few adverse systemic effects. On average a period of 2 to 4 hours is necessary for the substance to reach peak plasma concentration. 5 D06FJO DB09085 Tetracaine small molecule approved 94-24-6 264.369 C15H24N2O2 Q92736#Ryanodine receptor 2@Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha Not Available D08HQK DB09086 Eugenol small molecule approved 97-53-0 164.2011 C10H12O2 Q92731#Estrogen receptor beta@P10275#Androgen receptor@Q8NET8#Transient receptor potential cation channel subfamily V member 3 Not Available DB09087 Potassium alum small molecule approved 10043-67-1 258.205 AlKO8S2 The presence of potassium alum reduces swollen mucous membranes that result from inflammation of the nasal, gastrointestinal and urinary passages as well as in the presence of excessive secretions. The induction of the coagulation cascade will also stop bleeding.14 DB09088 Amylocaine small molecule approved 644-26-8 235.327 C14H21NO2 Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha Like all other local anesthetics, amylocaine acts as a membrane stabilizing drug that reversibly decreases the rate of depolarization and depolarization of excitable membranes 2. In this way, the conduction of neuronal signals for certain bodily movements can be blocked 2. In particular, when administered for spinal anesthesia, the resultant anesthesia can typically extend from the chest to the legs 2. DB09089 Trimebutine small molecule approved 39133-31-8 387.476 C22H29NO5 P20309#Muscarinic acetylcholine receptor M3@P08172#Muscarinic acetylcholine receptor M2@Q12791#Calcium-activated potassium channel subunit alpha-1@Q9Y691#Calcium-activated potassium channel subunit beta-2@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A Trimebutine is a spasmolytic agent that acts directly on smooth muscle to modulate gastric motility. It shows a "dual function" that stimulates or inhibits spontaneous contractions depending on the concentration and prior contractile activity in the preparation. Targeting ion conductance that regulates GI motility, trimebutine inhibits the inward calcium currents and calcium-dependent potassium currents in a concentration-dependent manner 2. At lower concentrations (1-10uM), trimebutine depolarizes the resting membrane potential without affecting the amplitude of contractions, which is thought to be mediated by inhibition of outward potassium currents. It is also shown to activate T-type Ca2+ channel and increase gastric emptying, intestinal and colonic contractility 1. At higher concentrations (100-300uM), reduced amplitude of spontaneous contractions and action potentials is thought to be mediated by inhibition of L-type Ca2+ channels and inward calcium current 2. Trimebutine mediates a local anesthetic action by acting as a weak agonist at mu opioid receptors. D0E0CT DB09090 Pinaverium small molecule approved 59995-65-2 511.52 C26H41BrNO4 Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S Pinaverium is a selective and specific voltage-dependent calcium channel blocker located on intestinal smooth muscle cells to inhibit calcium influx. It mediates various effects on the GI tract: it causes oesophageal, gastric and duodenal relaxation, relaxes the colon and intestines, inhibits colonic motility in response to food, hormonal or pharmacological stimuli, accelerates gastric emptying, and reduces contractions of the gallbladder and phasic contractions of sphincter of Oddi 10,5. At higher concentrations, pinaverium also exhibits very weak anticholinergic effects 10 but is not shown to display vasodilatory or anti-arrythmic actions 9. DB09091 Tixocortol small molecule approved 61951-99-3 378.53 C21H30O4S P04150#Glucocorticoid receptor@Q92769#Histone deacetylase 2 Tixocortol presents the characteristic of local action which reduces significantly the side effects of systemic glucocorticoids. Reports have demonstrated that gastrointestinal administration of tixocortol generates a decrease in abdominal pain, bleeding, and frequency of stools which resulted in an amelioration in the malabsorption laboratory tests. All the effects were independent of suppression of the pituitary-adrenal axis, which was shown by the absence of significant depression of cortisol.1 Administration of tixocortol as a nasal spray has been shown to respect nasal drainage by the ciliary beats of the pituitary mucosa.3 The actions of tixocortol have no effect on leukocyte count, blood glucose level, sodium urinary excretion, and immunosupressive activity on lymphocytes.9 DB09092 Xanthinol small molecule approved 2530-97-4 311.342 C13H21N5O4 Q8IKK7#Glyceraldehyde-3-phosphate dehydrogenase@P50213#Isocitrate dehydrogenase [NAD] subunit alpha, mitochondrial@Q02218#2-oxoglutarate dehydrogenase, mitochondrial@P40926#Malate dehydrogenase, mitochondrial@Q8IJC6#60S ribosomal protein L3 Reports indicate that xanthinol increases blood flow in the vascular beds. The use of xanthinol in clinical trials have reported improvements in the performance of healthy elderly individuals in short- and long-term memory tests.7 The later effect is explained by the enhancing on the cell metabolism and oxygen supply in the brain by the rise of ATP in erythrocytes which allows penetration into capillaries easier and a higher oxygen pressure in the capillary blood which improves oxygenation of surrounding tissue.1 DB09093 Chlortetracycline small molecule approved 57-62-5 478.88 C22H23ClN2O8 P84077#ADP-ribosylation factor 1@P04040#Catalase@P54762#Ephrin type-B receptor 1@P16233#Pancreatic triacylglycerol lipase@Q9UM07#Protein-arginine deiminase type-4 Tetracycline antibiotics are bacteriostatic agents which act to inhibit bacterial growth and reproduction 2. D0R6RC DB09094 Podophyllin small molecule approved 9000-55-9 1693.67 C88H92O34 Cell division is arrested and other cellular processes are impaired, gradually resulting in the disruption of cells and destruction of the tissue. DB00818 Propofol small molecule approved 2078-54-8 178.2707 C12H18O P47870#Gamma-aminobutyric acid receptor subunit beta-2@P28472#Gamma-aminobutyric acid receptor subunit beta-3@P35499#Sodium channel protein type 4 subunit alpha@Q99250#Sodium channel protein type 2 subunit alpha Propofol is a sedative-hypnotic agent for use in the induction and maintenance of anesthesia or sedation. Intravenous injection of a therapeutic dose of propofol produces hypnosis rapidly with minimal excitation, usually within 40 seconds from the start of an injection (the time for one arm-brain circulation). D0A3HB DB00819 Acetazolamide small molecule approved 59-66-5 222.245 C4H6N4O3S2 P00915#Carbonic anhydrase 1@P00918#Carbonic anhydrase 2@P22748#Carbonic anhydrase 4@O43570#Carbonic anhydrase 12@Q9ULX7#Carbonic anhydrase 14@P07451#Carbonic anhydrase 3@P43166#Carbonic anhydrase 7@P29972#Aquaporin-1 Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion, in the treatment of certain convulsive disorders and in the promotion of diuresis in instances of abnormal fluid retention. Acetazolamide is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides. D0E1SW DB00820 Tadalafil small molecule approved 171596-29-5 389.404 C22H19N3O4 O76074#cGMP-specific 3',5'-cyclic phosphodiesterase@Q9HCR9#Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A@P18545#Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma Tadalafil exerts a therapeutic effect in ED by increasing sexual stimulation-dependant smooth muscle relaxation in the penis, allowing the corpus cavernosum to fill with blood to produce an erection.2,3 Smooth muscle relaxation in the pulmonary vasculature helps to produce vasodilation in PAH which reduces blood pressure in the pulmonary arteries.3 In BPH, tadalafil may contribute to decreased smooth muscle cell proliferation which may reduce the size of the prostate and relieve the anatomical obstruction which produces urinary symptoms of BPH.4 The decreased affinity of tadalafil for PDE6 compared to other PDE5 inhibitors may explain the reduced incidence of visual side effects.8,9,2 D05MQK DB00821 Carprofen small molecule approved 53716-49-7 273.714 C15H12ClNO2 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Carprofen is a non-steroidal anti-inflammatory drug (NSAID) of the propionic acid class that includes ibuprofen, naproxen, and ketoprofen. It is no longer used in the clinical setting, but is approved for use in dogs. Carprofen is non-narcotic and has characteristic analgesic and antipyretic activity approximately equipotent to indomethacin in animal models. D0IT2X DB00822 Disulfiram small molecule approved 97-77-8 296.539 C10H20N2S4 P09172#Dopamine beta-hydroxylase@P05091#Aldehyde dehydrogenase, mitochondrial Disulfiram produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol. Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake, the concentration of acetaldehyde occurring in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. Accumulation of acetaldehyde in the blood produces a complex of highly unpleasant symptoms referred to hereinafter as the disulfiram-alcohol reaction. This reaction, which is proportional to the dosage of both disulfiram and alcohol, will persist as long as alcohol is being metabolized. Disulfiram does not appear to influence the rate of alcohol elimination from the body. Prolonged administration of disulfiram does not produce tolerance; the longer a patient remains on therapy, the more exquisitely sensitive he becomes to alcohol. D0X5SD DB00823 Ethynodiol diacetate small molecule approved 297-76-7 384.5085 C24H32O4 P03372#Estrogen receptor@P06401#Progesterone receptor Ethynodiol Diacetate is used as a female contraceptive. Ethynodiol Diacetate is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. Ethynodiol Diacetate tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries. DB00824 Enprofylline small molecule approved 41078-02-8 194.1906 C8H10N4O2 Q07343#cAMP-specific 3',5'-cyclic phosphodiesterase 4B@P29275#Adenosine receptor A2b@P27815#cAMP-specific 3',5'-cyclic phosphodiesterase 4A@P30542#Adenosine receptor A1@P29274#Adenosine receptor A2a@P0DMS8#Adenosine receptor A3 Enprofylline is a synthetic dimethylxanthine derivative structurally related to theophylline and caffeine. It antagonizes erythrocyte phosphodiesterase, increasing cAMP activity. D09AMZ DB00825 Levomenthol small molecule approved 2216-51-5 156.2652 C10H20O P41145#Kappa-type opioid receptor@O75762#Transient receptor potential cation channel subfamily A member 1@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A Menthol is a covalent organic compound made synthetically or obtained from peppermint or other mint oils. Menthol induces a cooling sensation on the skin upon inhalation, oral ingestion, or topical application by stimulating the cold-sensitive receptors expressed on the skin, without actually causing a drop in the skin temperature. DB00826 Natamycin small molecule approved 7681-93-8 665.733 C33H47NO13 Natamycin is an antifungal drug for topical ophthalmic administration. It is a tetraene polyene antibiotic derived from Streptomyces natalensis. It possesses in vitro activity against a variety of yeast and filamentous fungi, including Candida, Aspergillus, Cephalosporium, Fusarium and Penicillium. Although the activity against fungi is dose-related, natamycin is predominantly fungicidal. Natamycin is not effective in vitro against gram-positive or gram-negative bacteria. Topical administration appears to produce effective concentrations of natamycin within the corneal stroma but not in intraocular fluid. D02FEM DB00827 Cinoxacin small molecule approved 28657-80-9 262.2182 C12H10N2O5 Cinoxacin is a synthetic antibacterial agent with in vitro activity against many gram-negative aerobic bacteria, particularly strains of the Enterobacteriaceae family. Cinoxacin inhibits bacterial deoxyribonucleic acid (DNA) synthesis, is bactericidal, and is active over the entire urinary pH range. Cross resistance with nalidixic acid has been demonstrated. D07UXP DB00828 Fosfomycin small molecule approved 23155-02-4 138.059 C3H7O4P P0A749#UDP-N-acetylglucosamine 1-carboxyvinyltransferase Although used primarily to treat urinary tract infections, fosfomycin has been shown to act synergistically with other antibiotics against clinically relevant bacteria.1 There is also growing interest in the potential of fosfomycin to treat more complex infections since it has retained activity against many difficult-to-treat strains of bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant enterobacteria.7 Further, since fosfomycin has a unique and singular mechanism of action, the risk of cross-resistance with other antibiotics is low.6,5 D01GYT DB00829 Diazepam small molecule approved 439-14-5 284.74 C16H13ClN2O P28472#Gamma-aminobutyric acid receptor subunit beta-3 Diazepam is a benzodiazepine that exerts anxiolytic, sedative, muscle- relaxant, anticonvulsant and amnestic effects 9,10,6. Most of these effects are thought to result from facilitation of the action of gamma aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system 9,10,6. D07JVL DB00830 Phenmetrazine small molecule approved 134-49-6 177.2429 C11H15NO P23975#Sodium-dependent noradrenaline transporter@Q01959#Sodium-dependent dopamine transporter Phenmetrazine is a sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to dextroamphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. Phenmetrazine was originally sold under the tradename Preludin as an anorectic. It has since been removed from the market. It is by some considered to have a greater potential for addiction than the amphetamines, and has been abused in many countries, for example Sweden. D0M2MC DB00831 Trifluoperazine small molecule approved 117-89-5 407.496 C21H24F3N3S Q9NYX4#Neuron-specific vesicular protein calcyon@P35348#Alpha-1A adrenergic receptor@P0DP23#Calmodulin@P63316#Troponin C, slow skeletal and cardiac muscles@P26447#Protein S100-A4 Trifluoperazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Trifluoperazine has not been shown effective in the management of behaviorial complications in patients with mental retardation. D0R4OM DB00832 Phensuximide small molecule approved 86-34-0 189.2105 C11H11NO2 Phensuximide suppresses the paroxysmal three cycle per second spike and wave EEG pattern associated with lapses of consciousness in absence (petit mal) seizures. The frequency of attacks is reduced by depression of nerve transmission in the motor cortex. D06BYV DB00833 Cefaclor small molecule approved 53994-73-3 367.807 C15H14ClN3O4S D0PW7C DB00834 Mifepristone small molecule approved 84371-65-3 429.5937 C29H35NO2 P06401#Progesterone receptor@P04150#Glucocorticoid receptor@O75469#Nuclear receptor subfamily 1 group I member 2@P07288#Prostate-specific antigen D0Z4EI DB00835 Brompheniramine small molecule approved 86-22-6 319.239 C16H19BrN2 P70174#Histamine H1 receptor@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5 Brompheniramine is an antihistaminergic medication of the propylamine class. It is a first-generation antihistamine. In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Brompheniramine is a histamine H1 antagonist (or more correctly, an inverse histamine agonist) of the alkylamine class. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. D08VXO DB00836 Loperamide small molecule approved 53179-11-6 477.038 C29H33ClN2O2 P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A@P01189#Pro-opiomelanocortin@P0DP23#Calmodulin@Q14994#Nuclear receptor subfamily 1 group I member 3 Loperamide is a synthetic anti-diarrheal indicated for the control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease. Loperamide is also indicated for reducing the volume of discharge from ileostomies. In man, Loperamide prolongs the transit time of the intestinal contents. It reduces the daily fecal volume, increases the viscosity and bulk density, and diminishes the loss of fluid and electrolytes. Tolerance to the antidiarrheal effect has not been observed. Loperamide is an opioid receptor agonist and acts on the mu opioid receptors in the myenteric plexus large intestines; it does not affect the central nervous system like other opioids. It works specifically by decreasing the activity of the myenteric plexus which decreases the motility of the circular and longitudinal smooth muscles of the intestinal wall. This increases the amount of time substances stay in the intestine, allowing for more water to be absorbed out of the fecal matter. Loperamide also decreases colonic mass movements and suppresses the gastrocolic reflex. D0CS2F DB00838 Clocortolone small molecule approved 4828-27-7 410.907 C22H28ClFO4 P04150#Glucocorticoid receptor Like other topical corticosteroids, clocortolone has anti-inflammatory, antipruritic, and vasoconstrictive properties. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Clocortolone is a moderate potency topical corticosteroid that should not be used with occlusive dressings. It is recommended that treatment should be limited to 2 consecutive weeks and therapy should be discontinued when adequate results have been achieved. D00GOS DB00839 Tolazamide small molecule approved 1156-19-0 311.4 C14H21N3O3S Tolazamide is an oral blood glucose lowering drug of the sulfonylurea class. Tolazamide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which tolazamide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs. Some patients who are initially responsive to oral hypoglycemic drugs, including tolazamide, may become unresponsive or poorly responsive over time. Alternatively, tolazamide may be effective in some patients who have become unresponsive to one or more other sulfonylurea drugs. In addition to its blood glucose lowering actions, tolazamide produces a mild diuresis by enhancement of renal free water clearance. D09FJB DB00841 Dobutamine small molecule approved 34368-04-2 301.3801 C18H23NO3 P03372#Estrogen receptor@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor Dobutamine is a direct-acting inotropic agent whose primary activity results from stimulation of the beta-adrenoceptors of the heart while producing comparatively mild chronotropic, hypertensive, arrhythmogenic, and vasodilative effects. Dobutamine acts primarily on beta-1 adrenergic receptors, with negligible effects on beta-2 or alpha receptors. It does not cause the release of endogenous norepinephrine, as does dopamine. D0J7RK DB00842 Oxazepam small molecule approved 604-75-1 286.713 C15H11ClN2O2 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Benzodiazepines, including oxazepam, exert their sedative and anxiolytic effects by potentiating the effects of endogenous GABA, the primary inhibitory neurotransmitter in the CNS.10 Compared to other benzodiazepines, it has relatively low potency and a moderate duration of action.10 Oxazepam should be administered with caution to patients for whom a drop in blood pressure may lead to cardiac complications as, in rare cases, it may cause hypotension.14 D09LDR DB00843 Donepezil small molecule approved 120014-06-4 379.492 C24H29NO3 P29475#Nitric oxide synthase, brain@P22303#Acetylcholinesterase@P01584#Interleukin-1 beta@P06276#Cholinesterase@Q00653#Nuclear factor NF-kappa-B p100 subunit@P19838#Nuclear factor NF-kappa-B p105 subunit@P98066#Tumor necrosis factor-inducible gene 6 protein@Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B By inhibiting the acetylcholinesterase enzyme, donepezil improves the cognitive and behavioral signs and symptoms of Alzheimer's Disease, which may include apathy, aggression, confusion, and psychosis.8,15 D0NS6H DB00844 Nalbuphine small molecule approved 20594-83-6 357.4434 C21H27NO4 P41145#Kappa-type opioid receptor@P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor Nalbuphine is a synthetic opioid agonist-antagonist analgesic of the phenanthrene series. Nalbuphine's analgesic potency is essentially equivalent to that of morphine on a milligram basis. The opoioid antagonist activity of nalbuphine is about one-fourth to that of nalorphine and 10 times to that of pentazocine. Nalbuphine by itself has potent opioid antagonist activity at doses equal to or lower than its analgesic dose. When administered following or concurrent with mu agonist opioid analgesics (e.g., morphine, oxymorphone, fentanyl), nalbuphine may partially reverse or block opioid-induced respiratory depression from the mu agonist analgesic. Nalbuphine may precipitate withdrawal in patients dependent on opioid drugs. Nalbuphine should be used with caution in patients who have been receiving mu opioid analgesics on a regular basis. D01KQA DB00845 Clofazimine small molecule approved 2030-63-9 473.396 C27H22Cl2N4 P37231#Peroxisome proliferator-activated receptor gamma@P22001#Potassium voltage-gated channel subfamily A member 3 Clofazimine exerts a slow bactericidal effect on Mycobacterium leprae (Hansen's bacillus) due primarily to its action on the bacterial outer membrane, though there is some evidence that activity on the bacterial respiratory chain and ion transporters may play a role.2 It also exerts anti-inflammatory properties due to the suppression of T-lymphocyte activity. Clofazimine has a relatively long duration of action owing to its long residence time in the body, but is still administered daily. D0S5UH DB00846 Flurandrenolide small molecule approved 1524-88-5 436.5136 C24H33FO6 P04150#Glucocorticoid receptor Flurandrenolide is primarily effective because of its anti-inflammatory, antipruritic, and vasoconstrictive actions. D0Y2YP DB00847 Cysteamine small molecule approved 60-23-1 77.149 C2H7NS P49146#Neuropeptide Y receptor type 2 D0V0LB DB00848 Levamisole small molecule approved 14769-73-4 204.291 C11H12N2S P32297#Neuronal acetylcholine receptor subunit alpha-3@P10696#Alkaline phosphatase, placental-like@Q23022#Acetylcholine receptor subunit alpha-type unc-38@Q9N587#Acetylcholine receptor subunit alpha-type unc-63@Q27218#Acetylcholine receptor subunit beta-type lev-1@P48181#Acetylcholine receptor subunit beta-type unc-29 Levamisole is a synthetic imidazothiazole derivative that has been widely used in treatment of worm infestations in both humans and animals. As an anthelmintic, it probably works by targeting the nematode nicotinergic acetylcholine receptor. As an immunomodulator, it appears that Levamisole is an immunostimulant which has been shown to increase NK cells and activated T-cells in patients receiving this adjuvantly along with 5FU for Stage III colon cancer. D0CF2Q DB00849 Methylphenobarbital small molecule approved 115-38-8 246.2619 C13H14N2O3 Q13002#Glutamate receptor ionotropic, kainate 2@P42262#Glutamate receptor 2@P43681#Neuronal acetylcholine receptor subunit alpha-4@O75469#Nuclear receptor subfamily 1 group I member 2@P36544#Neuronal acetylcholine receptor subunit alpha-7 Methylphenobarbital, a barbiturate, is used in combination with acetaminophen or aspirin and caffeine for its sedative and relaxant effects in the treatment of tension headaches, migraines, and pain. Barbiturates act as nonselective depressants of the central nervous system (CNS), capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. In sufficiently high therapeutic doses, barbiturates induce anesthesia. D08UMH DB00850 Perphenazine small molecule approved 58-39-9 403.969 C21H26ClN3OS P21728#D(1A) dopamine receptor@P0DP23#Calmodulin@P14416#D(2) dopamine receptor Perphenazine is a piperazinyl phenothiazine, acts on the central nervous system, and has a greater behavioral potency than other phenothiazine derivatives whose side chains do not contain a piperazine moiety. It is a member of a class of drugs called phenothiazines, which are dopamine D1/D2 receptor antagonists. Perphenazine is 10 to 15 times as potent as chlorpromazine; that means perphenazine is a highly potent antipsychotic. In equivalent doses it has approximately the same frequency and severity of early and late extrapypramidal side-effects compared to Haloperidol. D02HED DB00851 Dacarbazine small molecule approved 4342-03-4 182.187 C6H10N6O Q14181#DNA polymerase alpha subunit B@P52209#6-phosphogluconate dehydrogenase, decarboxylating Dacarbazine is a synthetic analog of naturally occurring purine precursor 5-amino-1H-imidazole-4-carboxamide (AIC). After intravenous administration of dacarbazine, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours. 1 In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours. 1 The average cumulative excretion of unchanged DTIC in the urine is 40% of the injected dose in 6 hours. 1 DTIC is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein. D0Y7ZU DB00852 Pseudoephedrine small molecule approved 90-82-4 165.2322 C10H15NO P08913#Alpha-2A adrenergic receptor Pseudoephedrine causes vasoconstriction which leads to a decongestant effect.2,12,13,14,15,16,17,18 It has a short duration of action unless formulated as an extended release product.12,13,14,15,16,17,18 Patients should be counselled regarding the risk of central nervous system stimulation.12,14,17,18 D00HHS DB00853 Temozolomide small molecule approved 85622-93-1 194.1508 C6H6N6O2 D0C8EU DB00854 Levorphanol small molecule approved 77-07-6 257.3706 C17H23NO P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor Levorphanol is a potent synthetic opioid analgesic indicated for the management of moderate to severe pain or as a preoperative medication where an opioid analgesic is appropriate. Levorphanol is similar to morphine in its actions, however it is up to 8 times more potent than morphine. Levorphanol produces a degree of respiratory depression similar to that produced by morphine at equianalgesic doses, and like many mu-opioid drugs, levorphanol produces euphoria or has a positive effect on mood in many individuals. D0T3HY DB00855 Aminolevulinic acid small molecule approved 106-60-5 131.1299 C5H9NO3 P13716#Delta-aminolevulinic acid dehydratase The metabolism of aminolevulinic acid (ALA) is the first step in the biochemical pathway resulting in heme synthesis. Aminolevulinic acid is not a photosensitizer, but rather a metabolic precursor of protoporphyrin IX (PpIX), which is a photosensitizer. The synthesis of ALA is normally tightly controlled by feedback inhibition of the enzyme, ALA synthetase, presumably by intracellular heme levels. ALA, when provided to the cell, bypasses this control point and results in the accumulation of PpIX, which is converted into heme by ferrochelatase through the addition of iron to the PpIX nucleus. DB00856 Chlorphenesin small molecule approved 104-29-0 202.635 C9H11ClO3 Chlorphenesin is a muscle relaxant. It blocks nerve impulses (or pain sensations) that are sent to the brain. D0VB0U DB00857 Terbinafine small molecule approved 91161-71-6 291.4299 C21H25N Q92206#Squalene monooxygenase@Q92206#Squalene monooxygenase Terbinafine is an allylamine antifungal that inhibits squalene epoxidase (also known as squalene monooxygenase) to prevent the formation of ergosterol and cause an accumulation of squalene, weakening the cell wall of fungal cells.1,2,11 Terbinafine distributes into tissues and has a long terminal elimination half life, so the duration of action is long.1 Overdose with terbinafine is rare, even above the therapeutic dose, so the therapeutic index is wide.10,11 Patients taking oral terbinafine should have liver function tests performed prior to treatment to reduce the risk of liver injury.10 D01AYJ DB00859 Penicillamine small molecule approved 52-67-5 149.211 C5H11NO2S Penicillamine is a chelating agent used in the treatment of Wilson's disease. It is also used to reduce cystine excretion in cystinuria and to treat patients with severe, active rheumatoid arthritis unresponsive to conventional therapy. Penicillamine is used as a form of immunosuppression to treat rheumatoid arthritis. Penicillamine inhibits macrophages, decreases IL-1 and the number of T-lymphocytes, and prevents collagen cross linkage. In Wilson's disease it binds copper, allowing it to be eliminated in the urine. D08HZC DB00860 Prednisolone small molecule approved 50-24-8 360.444 C21H28O5 P04150#Glucocorticoid receptor Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.4 Prednisolone has a short duration of action as the half life is 2.1-3.5 hours.1 Corticosteroids have a wide therapeutic window as patients make require doses that are multiples of what the body naturally produces.4 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.4 D0D1SG DB00861 Diflunisal small molecule approved 22494-42-4 250.1976 C13H8F2O3 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Diflunisal is a nonsteroidal drug with analgesic, anti-inflammatory and antipyretic properties. It is a peripherally-acting non-narcotic analgesic drug. Habituation, tolerance and addiction have not been reported. Diflunisal is a difluorophenyl derivative of salicylic acid. Chemically, diflunisal differs from aspirin (acetylsalicylic acid) in two respects. The first of these two is the presence of a difluorophenyl substituent at carbon 1. The second difference is the removal of the 0-acetyl group from the carbon 4 position. Diflunisal is not metabolized to salicylic acid, and the fluorine atoms are not displaced from the difluorophenyl ring structure. D08LFZ DB00862 Vardenafil small molecule approved 224785-90-4 488.603 C23H32N6O4S O76074#cGMP-specific 3',5'-cyclic phosphodiesterase@P18545#Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma@Q13956#Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma Vardenafil is used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH). Part of the physiological process of erection involves the release of nitric oxide (NO) in the corpus cavernosum. This then activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in the corpus cavernosum, resulting in increased inflow of blood and an erection. Vardenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. This means that, with vardenafil on board, normal sexual stimulation leads to increased levels of cGMP in the corpus cavernosum which leads to better erections. Without sexual stimulation and no activation of the NO/cGMP system, vardenafil should not cause an erection. D0C9SY DB00863 Ranitidine small molecule approved 66357-35-5 314.4 C13H22N4O3S P25021#Histamine H2 receptor@P22303#Acetylcholinesterase Ranitidine decreases the secretion of gastric acid stimulated by food and drugs. It also reduces the secretion of gastric acid in hypersecretory conditions such as Zollinger-Ellison syndrome.6,11 Marked improvements in the appearance of the esophageal tissues have been observed by endoscopic imaging after ranitidine therapy.5,11 D0B8WN DB00864 Tacrolimus small molecule approved 104987-11-3 804.0182 C44H69NO12 P62942#Peptidyl-prolyl cis-trans isomerase FKBP1A Tacrolimus acts by reducing peptidyl-prolyl isomerase activity by binding to the immunophilin FKBP-12 (FK506 binding protein) creating a new complex. This inhibits both T-lymphocyte signal transduction and IL-2 transcription. Tacrolimus has similar activity to cyclosporine but rates of rejection are lower with tacrolimus. Tacrolimus has also been shown to be effective in the topical treatment of eczema, particularly atopic eczema. It suppresses inflammation in a similar way to steroids, but is not as powerful. An important dermatological advantage of tacrolimus is that it can be used directly on the face; topical steroids cannot be used on the face, as they thin the skin dramatically there. On other parts of the body, topical steroid are generally a better treatment. D06OMK DB00865 Benzphetamine small molecule approved 156-08-1 239.3553 C17H21N Q05940#Synaptic vesicular amine transporter@P08913#Alpha-2A adrenergic receptor@P35348#Alpha-1A adrenergic receptor@Q01959#Sodium-dependent dopamine transporter Benzphetamine, a phenylalkylamin, is related to amphetamine both chemically and pharmacologically. It is an anorectic agent indicated in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction. Benzphetamine is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, the amphetamines. Actions include central nervous system stimulation and elevation of blood pressure. Tachyphylaxis and tolerance have been demonstrated with all drugs of this class in which these phenomena have been looked for. D0T5UL DB00867 Ritodrine small molecule approved 26652-09-5 287.3535 C17H21NO3 P07550#Beta-2 adrenergic receptor@Q15746#Myosin light chain kinase, smooth muscle Beta-2 adrenergic receptors are located at sympathetic neuroeffector junctions of many organs, including uterus. Ritodrine is beta-2 adrenergic agonist. It stimulates beta-2 adrenergic receptor, increases cAMP level and decreases intracellular calcium concentration. The decrease of calcium concentration leads to a relaxation of uterine smooth muscle and, therefore, a decrease in premature uterine contractions. D00LFB DB00868 Benzonatate small molecule approved 104-31-4 603.7419 C30H53NO11 Q14524#Sodium channel protein type 5 subunit alpha Benzonatate suppresses cough associated with both acute and chronic respiratory conditions. Its works by desensitizing the pulmonary stretch receptors involved in the cough reflex. There are limited clinical trials of benzonatate; however, earlier studies demonstrated inhibition of experimentally-induced cough and subjectively-measured pathological cough by benzonatate.1 D0Q2ES DB00869 Dorzolamide small molecule approved 120279-96-1 324.44 C10H16N2O4S3 P00918#Carbonic anhydrase 2@P22748#Carbonic anhydrase 4@P00915#Carbonic anhydrase 1@P07451#Carbonic anhydrase 3 Dorzolamide is a carbonic anhydrase inhibitor that reduces elevated intraocular pressure in open-angle glaucoma or ocular hypertension. When used in combination with topic beta-adrenergic antagonists, dorzolamide has an additive effect of lowering intraocular pressure. The peak ocular hypotensive effect of dorzolamide is observed at about 2 hours following ophthalmic administration.2 D05UYW DB00870 Suprofen small molecule approved 40828-46-4 260.308 C14H12O3S P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Suprofen is a non-steroidal anti-inflammatory analgesic and antipyretic. Ophthalmic anti-inflammatory medicines are used in the eye to lessen problems that can occur during or after some kinds of eye surgery. Sometimes, the pupil of the eye gets smaller during an operation (pupil constriction), making it more difficult for the surgeon to reach some areas of the eye. Suprofen is used to help prevent this. D07BPS DB00871 Terbutaline small molecule approved 23031-25-6 225.2842 C12H19NO3 P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P08588#Beta-1 adrenergic receptor Terbutaline is a beta-2 adrenergic receptor agonist indicated to treat reversibly bronchospasm in asthmatic patients with bronchitis and emphysema.16,17 It has a short duration as the inhaled form is taken up to three times daily, and the therapeutic window is wide.16,17 D0M8RC DB00872 Conivaptan small molecule approved 210101-16-9 498.5744 C32H26N4O2 P37288#Vasopressin V1a receptor@P30518#Vasopressin V2 receptor Conivaptan is a nonpeptide, dual antagonist of arginine vasopressin (AVP) V1A and V2 receptors. The level of AVP in circulating blood is critical for the regulation of water and electrolyte balance and is usually elevated in both euvolemic and hypervolemic hyponatremia. The AVP effect is mediated through V2 receptors, which are functionally coupled to aquaporin channels in the apical membrane of the collecting ducts of the kidney. These receptors help to maintain plasma osmolality within the normal range by increasing permeability of the renal collecting ducts to water. Vasopressin also causes vasoconstriction through its actions on vascular 1A receptors. The predominant pharmacodynamic effect of conivaptan in the treatment of hyponatremia is through its V2 antagonism of AVP in the renal collecting ducts, an effect that results in aquaresis, or excretion of free water. Conivaptan's antagonist activity on V1A receptors may also cause splanchnic vasodilation, resulting in possible hypotension or variceal bleeding in patients with cirrhosis. The pharmacodynamic effects of conivaptan include increased free water excretion (i.e., effective water clearance [EWC]) generally accompanied by increased net fluid loss, increased urine output, and decreased urine osmolality. D0VU2X DB14596 Loteprednol etabonate small molecule approved 82034-46-6 466.96 C24H31ClO7 P04150#Glucocorticoid receptor Loteprednol etabonate (LE) belongs to a unique class of corticosteroids with potent anti-inflammatory effects designed to be active at the site of action 1,5. Animal studies have shown that LE has a binding affinity to steroid receptors that is 4.3 times greater than dexamethasone 5. This particular class of steroids consists of bioactive molecules whose in-vivo transformation to non-toxic substances can be predicted from their chemistry and knowledge of enzymatic pathways in the body 5. Cortienic acid is an inactive metabolite of hydrocortisone and analogs of cortienic acid are also devoid of corticosteroid activity 5. Specifically, LE is an ester derivative of one of these analogs, cortienic acid etabonate 5. In particular, LE possesses a metabolically labile 17 beta-chloromethyl ester function which was designed in order to be hydrolyzed to an inactive carboxylic acid moiety 1. This inactive metabolite is more hydrophilic and is thus readily eliminated from the body 1. LE also exhibits good ocular permeation properties and good skin permeation properties 1. DB00874 Guaifenesin small molecule approved 93-14-1 198.2158 C10H14O4 Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B Guaifenesin is categorized as an expectorant that acts by enhancing the output of phlegm (sputum) and bronchial secretions via decreasing the adhesiveness and surface tension of such material 9. Furthermore, guaifenesin elicits an increased flow of less viscous gastric secretions that subsequently promote ciliary action - all actions that ultimately change dry, unproductive coughing to coughs that are more productive and less frequent 9. Essentially, by decreasing the viscosity and adhesiveness of such secretions, guaifenesin enhances the efficacy of mucociliary activity in removing accumulated secretions from the upper and lower airway 9. DB00875 Flupentixol small molecule approved 2709-56-0 434.52 C23H25F3N2OS P28223#5-hydroxytryptamine receptor 2A@P35348#Alpha-1A adrenergic receptor@P28335#5-hydroxytryptamine receptor 2C@P11229#Muscarinic acetylcholine receptor M1 Flupentixol is an antipsychotic agent with anxiolytic and mild sedative actions. It exerts weak anticholinergic and adrenergic effects. It possesses antiemetic actions. As flupentixol works by antagonizing dopamine actions, it can cause extrapyramidal effects,11 mostly at doses greater than 10 mg. In clinical trials, flupentixol-induced extrapyramidal effects have been managed with anti-Parkinsonian drugs.3 Drug esterification in the intramuscular formulation of the drug results in slow release of the drug from the injection site and a prolonged duration of action.11 Flupentixol has been investigated for use in mild to moderate depression: compared to other antidepressant agents, flupentixol has a rapid onset of action, where antidepressive effects were observed within the first two to three days after administration.3 DB00876 Eprosartan small molecule approved 133040-01-4 424.513 C23H24N2O4S P30556#Type-1 angiotensin II receptor Angiotensin II, the principal pressor agent of the renin-angiotensin system, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme [kininase II]. It is responsible for effects such as vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Eprosartan selectively blocks the binding of angiotensin II to the AT1 receptor, which in turn leads to multiple effects including vasodilation, a reduction in the secretion of vasopressin, and reduction in the production and secretion of aldosterone. The resulting effect is a decrease in blood pressure. D0T7US DB00877 Sirolimus small molecule approved 53123-88-9 914.187 C51H79NO13 P42345#Serine/threonine-protein kinase mTOR Sirolimus is an immunosuppressant drug with antifungal and antitumour effects.2 In animal models, sirolimus prolonged allograft survival following various organ transplants and reversed an acute rejection of heart and kidney allografts in rats. Upon oral administration of 2 mg/day and 5 mg/day, sirolimus significantly reduced the incidence of organ rejection in low- to moderate-immunologic risk renal transplant patients at six months following transplantation compared with either azathioprine or placebo. In some studies, the immunosuppressive effect of sirolimus lasted up to six months after discontinuation of therapy: this tolerization effect is alloantigen-specific.8 Sirolimus potently inhibits antigen-induced proliferation of T cells, B cells, and antibody production.3 D03LJR DB00878 Chlorhexidine small molecule approved 55-56-1 505.447 C22H30Cl2N10 Chlorhexidine is a broad-spectrum antimicrobial with demonstrated activity against both gram-positive and gram-negative bacteria, yeasts, and viruses.2 Antimicrobial activity is dose-dependent - chlorhexidine is bacteriostatic at lower concentrations (0.02%-0.06%) and bactericidal at higher concentrations (>0.12%).2 Pharmacokinetic studies of oral chlorhexidine rinses indicate that approximately 30% of the active ingredient is retained in the mouth following rinsing, which is subsequently slowly released into oral fluids.11 This ability to adsorb to dentine, shared with tetracycline antibiotics such as doxycycline, is known as "substantivity" and is the result of chlorhexidine's positive charge - it is likely that this substantivity plays at least some role in chlorhexidine's antimicrobial activity, as its persistence on surfaces such as dentine prevent microbial colonization.7 D0V4GY DB00879 Emtricitabine small molecule approved 143491-57-0 247.247 C8H10FN3O3S Q72547#Reverse transcriptase/RNaseH Emtricitabine is a cytidine analog that competes with the natural substrate of HIV-1 reverse transcriptase to be incorporated into newly formed DNA, terminating its transcription.6 It is administered once daily so it has a long duration of action. Patients should be counselled regarding the risk of lactic acidosis and hepatomegaly with steatosis.6 D0S9SD DB00880 Chlorothiazide small molecule approved 58-94-6 295.723 C7H6ClN3O4S2 P55017#Solute carrier family 12 member 3@P00915#Carbonic anhydrase 1@P00918#Carbonic anhydrase 2 Like other thiazides, chlorothiazide promotes water loss from the body (diuretics). It inhibits Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate. After oral doses, 10-15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. D0M9WM DB00881 Quinapril small molecule approved 85441-61-8 438.5161 C25H30N2O5 P12821#Angiotensin-converting enzyme Quinapril is a prodrug of an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension or adjunct in the treatment of heart failure.1,2,6 Quinapril has a wide therapeutic window and a long duration of action as it is given in doses of 10-80mg once daily.6 D0I7SZ DB00882 Clomifene small molecule approved 911-45-5 405.96 C26H28ClNO P03372#Estrogen receptor@P04278#Sex hormone-binding globulin Clomifene (previously clomiphene) is an orally administered, non steroidal, ovulatory stimulant that acts as a selective estrogen receptor modulator (SERM). Clomifene can lead to multiple ovulation, and hence increase the risk of conceiving twins. In comparison to purified FSH, the rate of ovarian hyperstimulation syndrome is low. There may be an increased risk of ovarian cancer and weight gain. Clomifene is capable of interacting with estrogen-receptor-containing tissues, including the hypothalamus, pituitary, ovary, endometrium, vagina, and cervix. It may compete with estrogen for estrogen-receptor-binding sites and may delay replenishment of intracellular estrogen receptors. Clomifene initiates a series of endocrine events culminating in a preovulatory gonadotropin surge and subsequent follicular rupture. The first endocrine event, in response to a course of clomifene therapy, is an increase in the release of pituitary gonadotropins. This initiates steroidogenesis and folliculogenesis resulting in growth of the ovarian follicle and an increase in the circulating level of estradiol. Following ovulation, plasma progesterone and estradiol rise and fall as they would in a normal ovulatory cycle. D0CT9Y DB00883 Isosorbide dinitrate small molecule approved 87-33-2 236.1363 C6H8N2O8 P16066#Atrial natriuretic peptide receptor 1 Isosorbide Dinitrate is a moderate to long acting oral organic nitrate used for the relief and prophylactic management of angina pectoris. It relaxes the vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end- diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure. DB00884 Risedronic acid small molecule approved 105462-24-6 283.1123 C7H11NO7P2 P14324#Farnesyl pyrophosphate synthase Risedronate is a pyridine-based bisphosphonate that inhibits bone resorption caused by osteoclastsLabel. DB00885 Pemirolast small molecule approved 69372-19-6 228.2101 C10H8N6O Pemirolast is used for the prophylactic treatment of itching of the eye associated with allergic conjunctivitis. Pemirolast potassium is a mast cell stabilizer that inhibits the in vivo Type I immediate hypersensitivity reaction. Pemirolast inhibits the antigen-induced release of inflammatory mediators (e.g., histamine, leukotriene C4, D4, E4) from human mast cells. Allergic reactions lead to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis and vasodilatation (allowing blood fluids to enter the area to cause swelling). Pemirolast is a histamine H1 antagonist. It competes with histamine for the normal H1-receptor sites on effector cells of blood vessels to provide effective, temporary relief of watery and itchy eyes. D0K5LQ DB00887 Bumetanide small molecule approved 28395-03-1 364.416 C17H20N2O5S Q13621#Solute carrier family 12 member 1@P55011#Solute carrier family 12 member 2@Q9UP95#Solute carrier family 12 member 4@Q9H2X9#Solute carrier family 12 member 5@P13569#Cystic fibrosis transmembrane conductance regulator Bumetanide is a loop diuretic of the sulfamyl category to treat heart failure. It is often used in patients in whom high doses of furosemide are ineffective. There is however no reason not to use bumetanide as a first choice drug. The main difference between the two substances is in bioavailability. Bumetanide has more predictable pharmacokinetic properties as well as clinical effect. In patients with normal renal function, bumetanide is 40 times more effective than furosemide. D0R7HO DB00888 Mechlorethamine small molecule approved 51-75-2 156.054 C5H11Cl2N Mechlorethamine also known as mustine, nitrogen mustard, and HN2, is the prototype anticancer chemotherapeutic drug. Successful clinical use of mechlorethamine gave birth to the field of anticancer chemotherapy. The drug is an analogue of mustard gas and was derived from toxic gas warfare research. Mechlorethamine is a nitrogen mustard alkylating agent. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death. D03SSE DB00889 Granisetron small molecule approved 109889-09-0 312.417 C18H24N4O P46098#5-hydroxytryptamine receptor 3A Granisetron is a selective inhibitor of type 3 serotonergic (5-HT3) receptors. Granisetron has little or no affinity for other serotonin receptors, including 5-HT 1 , 5-HT 1A , 5-HT 1B/C , or 5-HT 2 ; for alpha 1 -, alpha 2 -, or beta-adrenoreceptors; for dopamine D 2 receptors; for histamine H 1 receptors; for benzodiazepine receptors; for picrotoxin receptors; or for opioid receptors. In most human studies, granisetron has had little effect on blood pressure, heart rate, or electrocardiogram (ECG). The drug is structurally and pharmacologically related to ondansetron, another selective inhibitor of 5-HT3 receptors. The serontonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting. D0J5KF DB00890 Dienestrol small molecule approved 13029-44-2 266.34 C18H18O2 P03372#Estrogen receptor@P04278#Sex hormone-binding globulin Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH). D09ZQN DB00891 Sulfapyridine small molecule approved 144-83-2 249.289 C11H11N3O2S P0C002#Dihydropteroate synthase type-1 Sulfapyridine is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus. D0D4CY DB00892 Oxybuprocaine small molecule approved 99-43-4 308.4158 C17H28N2O3 Q9Y5Y9#Sodium channel protein type 10 subunit alpha Oxybuprocaine is a local anaesthetic. It may be less irritating than tetracaine, and the onset and duration of action are similar to tetracaine. D0H2SY DB00894 Testolactone small molecule approved 968-93-4 300.3921 C19H24O3 P11511#Aromatase Testolactone is a synthetic anti-neoplastic agent that is structurally distinct from the androgen steroid nucleus in possessing a six-membered lactone ring in place of the usual five-membered carbocyclic D-ring. Despite some similarity to testosterone, testolactone has no in vivo androgenic effect. No other hormonal effects have been reported in clinical studies in patients receiving testolactone. D0C7JF DB00895 Benzylpenicilloyl polylysine small molecule approved 31855-75-1 626.765 C28H46N6O8S P30273#High affinity immunoglobulin epsilon receptor subunit gamma@P12319#High affinity immunoglobulin epsilon receptor subunit alpha Benylpenicilloyl polylysine is penicilloyl bound to polylysine and is considered to be the major determinant of penicillin metabolism; it is used as a skin-testing reagent to detect immunoglobulin E antibodies in people with a history of penicillin allergy. If skin testing using benzylpenicilloyl and penicillin G (as the sole source of minor determinants) is negative, approximately 97% of patients with a negative skin test will tolerate penicillin. DB00896 Rimexolone small molecule approved 49697-38-3 370.533 C24H34O3 P04150#Glucocorticoid receptor Rimexolone is a glucocorticoid corticosteroid for systemic use. Corticosteroids suppress the inflammatory response to a variety of inciting agents of a mechanical, chemical, or immunological nature. They inhibit edema, cellular infiltration, capillary dilatation, fibroblastic proliferation, deposition of collagen and scar formation associated with inflammation. D0D2TN DB00897 Triazolam small molecule approved 28911-01-5 343.21 C17H12Cl2N4 P28472#Gamma-aminobutyric acid receptor subunit beta-3 A short-acting benzodiazepine used as a hypnotic agent in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. Triazolam has a shorter half-life than chlordiazepoxide, flurazepam, and prazepam and does not generate active metabolites. D0U3LS DB00898 Ethanol small molecule approved 64-17-5 46.0684 C2H6O P23415#Glycine receptor subunit alpha-1 Alcohol produces injury to cells by dehydration and precipitation of the cytoplasm or protoplasm. This accounts for its bacteriocidal and antifungal action. When alcohol is injected in close proximity to nerve tissues, it produces neuritis and nerve degeneration (neurolysis). Ninety to 98% of ethanol that enters the body is completely oxidized. Ethanol is also used as a cosolvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol also binds to GABA, glycine, NMDA receptors and modulates their effects. Ethanol is also metabolised by the hepatic enzyme alcohol dehydrogenase. D00AMQ DB00899 Remifentanil small molecule approved 132875-61-7 376.4467 C20H28N2O5 P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor Remifentanil is an opioid agonist with rapid onset and peak effect and ultra-short duration of action. The opioid activity of remifentanil is antagonized by opioid antagonists such as naloxone. The analgesic effects of remifentanil are rapid in onset and offset. Its effects and side effects are dose dependent and similar to other opioids. Remifentanil in humans has a rapid blood-brain equilibration half-time of 1 ± 1 minutes (mean ± SD) and a rapid onset of action. D0T5OX DB00900 Didanosine small molecule approved 69655-05-6 236.2273 C10H12N4O3 Q72547#Reverse transcriptase/RNaseH@P00491#Purine nucleoside phosphorylase Didanosine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Didanosine is a hypoxanthine attached to the sugar ring, unlike other nucleoside analogues. Didanosine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. Didanosine is effective against HIV, and usually used in combination with other antiviral therapy. Switching from long term AZT treatment to didanosine has been shown to be beneficial. Didanosine has weak acid stability and therefore, it is often combined with an antacid. D06FDR DB00902 Methdilazine small molecule approved 1982-37-2 296.43 C18H20N2S P70174#Histamine H1 receptor In allergic reactions an allergen interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Methdilazine is a histamine H1 antagonist. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. D0LR0R DB00903 Etacrynic acid small molecule approved 58-54-8 303.138 C13H12Cl2O4 Q13621#Solute carrier family 12 member 1@P05023#Sodium/potassium-transporting ATPase subunit alpha-1@Q9UJU2#Lymphoid enhancer-binding factor 1@P09211#Glutathione S-transferase P Ethacrynic acid is a monosulfonamyl loop or high ceiling diuretic. Ethacrynic acid acts on the ascending limb of the loop of Henle and on the proximal and distal tubules. Urinary output is usually dose dependent and related to the magnitude of fluid accumulation. Water and electrolyte excretion may be increased several times over that observed with thiazide diuretics, since ethacrynic acid inhibits reabsorption of a much greater proportion of filtered sodium than most other diuretic agents. Therefore, ethacrynic acid is effective in many patients who have significant degrees of renal insufficiency. Ethacrynic acid has little or no effect on glomerular filtration or on renal blood flow, except following pronounced reductions in plasma volume when associated with rapid diuresis. DB00904 Ondansetron small molecule approved 99614-02-5 293.363 C18H19N3O P46098#5-hydroxytryptamine receptor 3A@Q13639#5-hydroxytryptamine receptor 4@P35372#Mu-type opioid receptor@P08908#5-hydroxytryptamine receptor 1A@P28222#5-hydroxytryptamine receptor 1B Ondansetron is a highly specific and selective serotonin 5-HT3 receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors Label, 3,4. The serotonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema Label, 3,4. The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents, suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract Label, 3,4. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting Label, 3,4. D0K7WK DB00905 Bimatoprost small molecule approved 155206-00-1 415.5656 C25H37NO4 P43088#Prostaglandin F2-alpha receptor@P34995#Prostaglandin E2 receptor EP1 subtype@P43115#Prostaglandin E2 receptor EP3 subtype High intraocular pressure is a major risk factor for glaucoma-related visual field loss. A linear relationship exists between intraocular pressure and the risk of damaging the optic nerve, which can lead to considerable visual impairment.13 Therefore, conditions such as ocular hypertension and glaucoma can cause dangerous elevations of intraocular pressure. Bimatoprost rapidly decreases intraocular pressure and reduces the risk for visual field loss from ocular hypertension due to various causes.13 D0Q2XF DB00906 Tiagabine small molecule approved 115103-54-3 375.548 C20H25NO2S2 P30531#Sodium- and chloride-dependent GABA transporter 1 Tiagabine is used primarily as an anticonvulsant for the adjunctive treatment of epilepsy. The precise mechanism by which Tiagabine exerts its antiseizure effect is unknown, although it is believed to be related to its ability to enhance the activity of gamma aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Tiagabine binds to recognition sites associated with the GABA uptake carrier. It is thought that, by this action, Tiagabine blocks GABA uptake into presynaptic neurons, permitting more GABA to be available for receptor binding on the surfaces of post-synaptic cells. D0ED7U DB00907 Cocaine small molecule approved 50-36-2 303.3529 C17H21NO4 Q01959#Sodium-dependent dopamine transporter@P23975#Sodium-dependent noradrenaline transporter@Q86DI9#Sodium channel protein@P31645#Sodium-dependent serotonin transporter@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@Q99720#Sigma non-opioid intracellular receptor 1@P23141#Liver carboxylesterase 1 Cocaine is a local anesthetic indicated for the introduction of local (topical) anesthesia of accessible mucous membranes of the oral, laryngeal and nasal cavities. D04XPW DB00908 Quinidine small molecule approved 56-54-2 324.4168 C20H24N2O2 Q14524#Sodium channel protein type 5 subunit alpha@O00180#Potassium channel subfamily K member 1@Q9Y257#Potassium channel subfamily K member 6@Q12809#Potassium voltage-gated channel subfamily H member 2@P35348#Alpha-1A adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor Quinidine, a hydantoin anticonvulsant, is used alone or with phenobarbital and other anticonvulsants to treat tachyarrhythmias, idiopathic ventricular fibrillation, Brugada syndrome, and short QT syndrome.1 Quinidine causes a marked prolongation of the QT interval in a dose-related manner.1,2 This can lead to increased ventricular automaticity and polymorphic ventricular tachycardias, such as torsades de pointes.2 DB00909 Zonisamide small molecule approved 68291-97-4 212.226 C8H8N2O3S Q14524#Sodium channel protein type 5 subunit alpha@Q99250#Sodium channel protein type 2 subunit alpha@Q9NY72#Sodium channel subunit beta-3@Q8IWT1#Sodium channel subunit beta-4 Zonisamide is a sulfonamide and therefore unrelated to other seizure medications. The mechanism is not know but it may block sodium and calcium channels. Blocking of these channels may prevent neuronal hypersynchronization. Sonisamide has also been found to potentiate dopaminergic and serotonergic neurotransmission but does not appear to potentiate syanptic activity by GABA (gamma amino butyric acid). D09ZIS DB00910 Paricalcitol small molecule approved 131918-61-1 416.6365 C27H44O3 P11473#Vitamin D3 receptor Secondary hyperparathyroidism is characterized by an elevation in parathyroid hormone (PTH) associated with inadequate levels of active vitamin D hormone. The source of vitamin D in the body is from synthesis in the skin and from dietary intake. Vitamin D requires two sequential hydroxylations in the liver and the kidney to bind to and to activate the vitamin D receptor (VDR). The endogenous VDR activator, calcitriol [1,25(OH)2 D3], is a hormone that binds to VDRs that are present in the parathyroid gland, intestine, kidney, and bone to maintain parathyroid function and calcium and phosphorus homeostasis, and to VDRs found in many other tissues, including prostate, endothelium and immune cells. VDR activation is essential for the proper formation and maintenance of normal bone. In the diseased kidney, the activation of vitamin D is diminished, resulting in a rise of PTH, subsequently leading to secondary hyperparathyroidism and disturbances in the calcium and phosphorus homeostasis.1 Decreased levels of 1,25(OH)2 D3 have been observed in early stages of chronic kidney disease. The decreased levels of 1,25(OH)2 D3 and resultant elevated PTH levels, both of which often precede abnormalities in serum calcium and phosphorus, affect bone turnover rate and may result in renal osteodystrophy. An in vitro study indicates that paricalcitol is not an inhibitor of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A at concentrations up to 50 nM (21 ng/mL). D0N1TP DB00911 Tinidazole small molecule approved 19387-91-8 247.272 C8H13N3O4S Tinidazole is a synthetic antiprotozoal agent. Tinidazole demonstrates activity both in vitro and in clinical infections against the following protozoa: Trichomonas vaginalis, Giardia duodenalis (also termed G. lamblia), and Entamoeba histolytica. Tinidazole does not appear to have activity against most strains of vaginal lactobacilli. DB00912 Repaglinide small molecule approved 135062-02-1 452.5857 C27H36N2O4 P37231#Peroxisome proliferator-activated receptor gamma D0N5YA DB00913 Anileridine small molecule approved 144-14-9 352.4699 C22H28N2O2 P35372#Mu-type opioid receptor Anileridine, a potent analgesic, is an analog of pethidine. Anileridine is useful for the relief of moderate to severe pain. It may also be used as an analgesic adjunct in general anesthesia in the same manner as meperidine to reduce the amount of anesthetic needed, to facilitate relaxation, and to reduce laryngospasm. In addition, anileridine exerts mild antihistaminic, spasmolytic and antitussive effects. Anileridine's main pharmacologic action is exerted on the CNS. Respiratory depression, when it occurs, is of shorter duration than that seen with morphine or meperidine when equipotent analgesic doses are used. D0X6HD DB00914 Phenformin small molecule approved 114-86-3 205.2596 C10H15N5 Q13131#5'-AMP-activated protein kinase catalytic subunit alpha-1@Q15842#ATP-sensitive inward rectifier potassium channel 8 Used to treat diabetes, phenformin is a biguanide (contains 2 guanidino groups) hypoglycemic agent with actions and uses similar to those of metformin (Glucophage). Both drugs work by (1) decreasing the absorption of glucose by the intestines, (2) decreasing the production of glucose in the liver, and by (3) increasing the body's ability to use insulin more effectively. More specifically, phenformin improves glycemic control by improving insulin sensitivity. Phenformin is generally considered to be associated with an unacceptably high incidence of actic acidosis. In general biguanides should be used only in stable type II diabetics who are free of liver, kidney and cardiovascular problems and who cannot be controlled with diet. D07XPE DB00915 Amantadine small molecule approved 768-94-5 151.2487 C10H17N Q8TCU5#Glutamate receptor ionotropic, NMDA 3A@P36544#Neuronal acetylcholine receptor subunit alpha-7@P43681#Neuronal acetylcholine receptor subunit alpha-4@P32297#Neuronal acetylcholine receptor subunit alpha-3 Amantadine is an antiviral drug which also acts as an antiparkinson agent, for which it is usually combined with L-DOPA when L-DOPA responses decline (probably due to tolerance). It is a derivate of adamantane, like a similar drug rimantadine. The mechanism of action of amantadine in the treatment of Parkinson's disease and drug-induced extrapyramidal reactions is not known. It has been shown to cause an increase in dopamine release in the animal brain, and does not possess anticholinergic activity. D02KRS DB00916 Metronidazole small molecule approved 443-48-1 171.154 C6H9N3O3 O25608#Oxygen-insensitive NADPH nitroreductase Metronidazole treats amebiasis, trichomoniasis, and giardiasis, exerting both antibacterial and antiprotozoal activities.16 Metronidazole is an effective treatment for some anaerobic bacterial infections.11 Metronidazole has shown antibacterial activity against the majority of obligate anaerobes, however, during in vitro studies, it does not demonstrate significant action against facultative anaerobes or obligate aerobes.14 The nitro group reduction of metronidazole by anaerobic organisms is likely responsible for the drug's antimicrobial cytotoxic effects, causing DNA strand damage to microbes.5,7 D0A2ZX DB00917 Dinoprostone small molecule approved 363-24-6 352.4651 C20H32O5 P43116#Prostaglandin E2 receptor EP2 subtype@P34995#Prostaglandin E2 receptor EP1 subtype@P43115#Prostaglandin E2 receptor EP3 subtype@P35408#Prostaglandin E2 receptor EP4 subtype@Q9Y5Y4#Prostaglandin D2 receptor 2 Dinoprostone is equivalent to prostaglandin E2 (PGE2). It stimulates labor and delivery by stimulating the uterine, and thus terminates pregnancy. Dinoprostone is also capable of stimulating the smooth muscle of the gastrointestinal tract of man. This activity may be responsible for the vomiting and/or diarrhea that is not uncommon when dinoprostone is used to terminate pregnancy. D06FEA DB09095 Difluocortolone small molecule approved 2607-06-9 394.459 C22H28F2O4 P12429#Annexin A3@P04150#Glucocorticoid receptor Diflucortolone is a steroid with the properties of being an anti-inflammatory, antipruritic and vasoconstrictive.1 Its activity causes the vasoconstriction of the blood vessels and thus a decrease in the release of inflammatory substances. These actions produce the effect of skin soothed and elimination of the symptoms.4 DB09096 Benzoyl peroxide small molecule approved 94-36-0 242.2268 C14H10O4 P04040#Catalase@Q6NSD4#Glutathione peroxidase Benzoyl peroxide is a topical treatment for acne that generates free radicals to break down comedones and increase the rate of epithelial cell turnover.1,3,4,5,9,10,11,12 It has a short duration of action as its active free radical metabolites quickly react to form inactive metabolites.1 The therapeutic index is wide, as overdoses are rare, however patients may still experience skin peeling.9,10,11,12 Patients should be counselled regarding increased risks of skin irritation, dryness, and sunburn.9,10,11,12 D04DXN DB09097 Quinagolide small molecule approved 87056-78-8 395.56 C20H33N3O3S P14416#D(2) dopamine receptor@P21728#D(1A) dopamine receptor Quinagolide achieves long-lasting reduction in prolactin levels in a dose-proportional effect via selectively targeting D2 receptors as an agonist. It potently suppresses both basal and stimulated serum prolactin levels by exerting a strong inhibitory effect on the secretion of the anterior pituitary hormone prolactin. D0W9ZF DB09099 Somatostatin small molecule approved 38916-34-6 1637.9 C76H104N18O19S2 P30872#Somatostatin receptor type 1@P30874#Somatostatin receptor type 2@P32745#Somatostatin receptor type 3@P31391#Somatostatin receptor type 4@P35346#Somatostatin receptor type 5 Somatostatin is an endogenous peptide hormone that is secreted by the central nervous system, gastrointestinal tract, retina, peripheral neurons and pancreatic D cells of the islets of Langerhans. It exhibits several biological roles but predominantly exerts an inhibitory effect on secretion of other hormones and transmitters 1. While distribution of two active isoforms of somatostatin is similar, SST-14 is more predominant in the enteric neurons and peripheral nerves whereas SST-28 is more prominent in the retina and intestinal mucosal cells 1. DB09101 Elvitegravir small molecule approved 697761-98-1 447.884 C23H23ClFNO5 Q7ZJM1#Integrase Not Available D0QD1G DB09102 Daclatasvir small molecule approved 1009119-64-5 738.89 C40H50N8O6 D09SGV DB09104 Magnesium hydroxide small molecule approved 1309-42-8 58.32 H2MgO2 As an antacid, magnesium hydroxide suspension neutralizes gastric acid by reacting with hydrochloric acid in the stomach to form magnesium chloride and water. It is practically insoluble in water and does not have any effect until it reacts with the hydrochloric acid in the stomach. There, it decreases the direct acid irritant effect and increases the pH in the stomach leading to inactivation of pepsin. Magnesium hydroxide enhances the integrity of the mucosal barrier of the stomach as well as improving the tone of both the gastric and esophageal sphincters. DB09110 Coenzyme M small molecule approved 3375-50-6 142.197 C2H6O3S2 Mesna binds to and inactivates acrolein there by preventing or reducing bladder problems DB09112 Nitrous acid small molecule approved 7782-77-6 47.0134 HNO2 P69905#Hemoglobin subunit alpha@P68871#Hemoglobin subunit beta@P02144#Myoglobin Sodium nitrite reverses cyanide toxicity and produces blood vessel dilation 1. DB09114 Colfosceril palmitate small molecule approved 63-89-8 734.0389 C40H80NO8P Colfosceril palmitate has shown to significantly reduce the risk of pneumothoraces, pulmonary interstitial emphysema and mortality. Unlike naturals surfactants, colfosceril palmitate reduces the risk of bronchopulmonary dysplasia, intraventricular hemorrhage and patent ductus arteriosus.5 In clinical placebo-controlled trials, there was a significant reduction in the number of deaths attributed to hyaline membrane disease, the incidence of pulmonary air leaks, oxygen requirements and mean airway pressure.6 Some reports have indicated a lack of therapeutic effect due to the absence of surfactant protein.7 D0A1XS DB09115 Diiodohydroxyquinoline small molecule approved 83-73-8 396.954 C9H5I2NO Not Available DB09116 Calcium carbimide small molecule approved 156-62-7 80.103 CCaN2 P48448#Aldehyde dehydrogenase family 3 member B2 Administration of calcium carbimide causes a syndrome characterized by intense flushing, rapid pulse, panting respiration and perception of acetaldehyde in the exhaled breath. This syndrome remains for a few hours after alcohol consumption and it stops completeley after 24 hours. This syndrome is caused by the accumulation of acetaldehyde and altered vascular reaction.2 Therefore, the more the alcohol consumption the more the adverse effects caused by acetaldehyde accumulation. D0A9KF DB09117 Paraldehyde small molecule approved 123-63-7 132.1577 C6H12O3 Paraldehyde blocks neuromuscular transmission 3. D0P9EA DB09118 Stiripentol small molecule approved 49763-96-4 234.295 C14H18O3 P07195#L-lactate dehydrogenase B chain@P00338#L-lactate dehydrogenase A chain@P28472#Gamma-aminobutyric acid receptor subunit beta-3 Stiripentol is an orphan drug that effectively reduces seizure frequency in infantile epilepsy as an adjunct therapy and also exhibits a therapeutic advantage in improving the efficacy of other antiepileptic drugs. It potentiates GABA transmission by elevating the levels of the inhibitory neurotransmitters in the brain 2. Stiripentol is a positive allosteric modulator of GABA-A receptors in the brain that enhances the opening duration of the channel by binding to a site different than the benzodiazepine binding site 1. Reduced synaptosomal uptake of GABA and/or inhibition of GABA transaminase may also explain the role of stiripentol in reducing the events of seizure 5. The anticonvulsant activity of stiripentol is age-dependent, with increased efficacy in younger patients 4. D02XSA DB09119 Eslicarbazepine acetate small molecule approved 236395-14-5 296.326 C17H16N2O3 Q99571#P2X purinoceptor 4 Eslicarbazepine acetate is associated with a dose- and concentration-dependant increase in heart rate and prolongation of PR interval. DB09120 Zucapsaicin small molecule approved 25775-90-0 305.4119 C18H27NO3 DB09121 Aurothioglucose small molecule approved 12192-57-3 392.18 C6H11AuO5S Q08828#Adenylate cyclase type 1@Q08462#Adenylate cyclase type 2@O95622#Adenylate cyclase type 5 After administration, patient serum levels of gold rise sharply but decline over the following week 6. Peak levels with aqueous preparations are higher and decline faster than those with oily preparations 6. Regular weekly administration produces a continuous rise in the basal value for several months, after which the serum level becomes relatively stable 6. After a standard weekly dose, considerable individual variation in the levels of gold can be observed 6. A steady decline in gold levels occurs when the interval between injections is lengthened, and small amounts may be found in the serum for months after discontinuation of therapy 6. The incidence of toxic reactions is seemingly unrelated to the plasma level of gold, but may perhaps be more associated with the total cumulative content of gold in the body 6. D0A4BR DB09123 Dienogest small molecule approved 65928-58-7 311.425 C20H25NO2 P06401#Progesterone receptor@P10275#Androgen receptor Dienogest exhibits a very potent progestagenic effect in the endometrium, and causes endometrial atrophy after prolonged use 2 . It also mediates an antiandrogenic effect that is equivalent to approximately one third that of cyproterone acetate 5. A dose of 2 mg inhibits the growth of ovarian follicles at 10 mm and maintains the concentration of progesterone at a low level, but has a weak inhibitory effect on FSH and LH. 1mg/kg of dienogest also directly inhibits ovulation 2. In clinical trials composing of patients with endometriosis, dienogest therapy effectively reduced painful symptoms and endometriotic lesions associated with the disorder 1. DB09124 Medrogestone small molecule approved 977-79-7 340.507 C23H32O2 P06401#Progesterone receptor Medrogestone was created as a more potent and orally active option of progesterone. In pre-clinical trials, medrogestone was proven to have four times more progestational activity than progesterone with a similar duration effect than the one found for 17-hydroxyprogesterone. Medrogestone was also able to maintain pregnancy and prevented ovulation in ovariectomized rats. Administration of medrogestone, alone or with premarin, prevented pregnancy, as well as it suppressed ovarian weight increase by nearly 100% of the tested individuals. Medrogestone does not produce any androgenic effect but it presented a marked anti-androgenic effect. It did not present an oestrogenic effect, nor changes in organ weight or histological appearance in adrenal glands or thymus and it does not present any anti-inflammatory effects.1 DB09125 Potassium citrate small molecule approved 866-84-2 306.394 C6H5K3O7 Potassium citrate induces changes in the urine which renders urine less susceptible to the formation of crystals and stones from salts e.g. calcium oxalate, calcium phosphate and uric acid. Increased citrate levels in the urine will make complexation with calcium which decrease the calcium ion activity and decrease the chance for the formation of calcium phosphate crystals. DB09128 Brexpiprazole small molecule approved 913611-97-9 433.57 C25H27N3O2S P08908#5-hydroxytryptamine receptor 1A@P28223#5-hydroxytryptamine receptor 2A@P18825#Alpha-2C adrenergic receptor@P35368#Alpha-1B adrenergic receptor Not Available DB09129 Chromic chloride small molecule approved 10025-73-7 158.355 Cl3Cr P06213#Insulin receptor Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Providing chromium during TPN helps prevent deficiency symptoms including impaired glucose tolerance, ataxia, peripheral neuropathy and a confusional state similar to mild/moderate hepatic encephalopathy. DB09130 Copper small molecule approved 7440-50-8 63.546 Cu P05067#Amyloid beta A4 protein@P50250#Adenosylhomocysteinase@P62807#Histone H2B type 1-C/E/F/G/I@Q8IKK7#Glyceraldehyde-3-phosphate dehydrogenase@P15531#Nucleoside diphosphate kinase A@P10412#Histone H1.4@Q06830#Peroxiredoxin-1@P05109#Protein S100-A8@P08865#40S ribosomal protein SA@P63261#Actin, cytoplasmic 2 Copper is incorporated into many enzymes throughout the body as an essential part of their function 2. Copper ions are known to reduce fertility when released from copper-containing IUDs 3. D01WMJ DB09131 Cupric Chloride small molecule approved 7447-39-4 134.452 Cl2Cu P04070#Vitamin K-dependent protein C@P04080#Cystatin-B Copper is an essential nutrient which serves as a co factor for serum ceruloplasmin, an oxidase necessary for proper formation of the iron carrier protein, transferrin. Copper also helps maintain normal rates of red and white blood cell formation. Providing copper during Total Parenteral Nutrition helps prevent development of the following deficiency symptoms: Leukopenia, neutropenia, anemia, depressed ceruloplasmin levels, impaired transferrin formation, secondary iron deficiency and osteoporosis. D0M5YS DB09132 Gadoteric acid small molecule approved 72573-82-1 558.65 C16H25GdN4O8 Gadoterate affects proton relaxation times and consequently the MR signal, and the contrast obtained is characterized by the relaxivity of the gadoterate molecule. The relaxivity values for gadoterate are similar across the spectrum of magnetic field strengths used in clinical MRI (0.2 - 1.5 T). DB09133 Iothalamic acid small molecule approved 2276-90-6 613.916 C11H9I3N2O4 Not Available DB09134 Ioversol small molecule approved 87771-40-2 807.115 C18H24I3N3O9 The contrast enhancement obtained with ioversol is related to iodine content. Immediately after ioversol is injected, a peak in iodine plasma levels can be detected. However, depending on the organ being imaged, the time to maximum contrast will vary.2 The time to maximum contrast enhancement will range from the time iodine plasma levels reach their highest concentration to one hour after intravenous bolus administration. The delay between a peak in iodine plasma levels and maximum contrast enhancement is partly due to the accumulation of iodine-containing medium within a lesion and outside the blood pool.2 D0U1ZD DB09135 Ioxilan small molecule approved 107793-72-6 791.116 C18H24I3N3O8 As with other iodinated contrast agents the degree of contrast enhancement is directly related to the iodine content in the administered dose. DB09136 Isosulfan blue small molecule approved 748080-29-7 545.69 C27H33N2O6S2 Following subcutaneous administration, Lymphazurin 1% binds to serum proteins and is picked up by the lymphatic vessels. Thus, the lymphatic vessels are delineated by the blue dye. D0P2YD DB09137 Technetium Tc-99m mebrofenin small molecule approved 1415247-71-0 486.136 C15H19BrN2O5Tc Not Available DB09138 Technetium Tc-99m medronate small molecule approved 121524-79-6 305.906 CH6O8P2Tc Not Available DB09139 Technetium Tc-99m oxidronate small molecule approved 72945-61-0 290.906 CH6O7P2Tc The technetium is generated in a molibdene generator. Technetium Tc-99m presents a reduction of gamma emission after 6 hours and it is considered a quasi-stable molecule.5 The visualization of bone lesions is possible since there is an altered uptake in areas of abnormal osteogenesis.4 The principal photon used for detection is the gamma-2 with an energy of 140.5 keV.5 Its use for bone examination should be performed 2 hours after initial injection with a recommended activity on the range of 370-740 MBq.8 DB09140 Oxygen small molecule approved 7782-44-7 31.9988 O2 P33517#Cytochrome c oxidase subunit 1@Q9Y5S8#NADPH oxidase 1 Oxygen therapy improves effective cellular oxygenation, even at a low rate of tissue perfusion. Oxygen molecules adjust hypoxic ventilatory drive by acting on chemoreceptors on carotid bodies that sequentially relay sensory information to the higher processing centers in brainstem. It also attenuates hypoxia-induced mitochondrial depolarization that generates reactive oxygen species and/or apoptosis. DB09142 Sincalide small molecule approved 25126-32-3 1143.27 C49H62N10O16S3 Not Available DB09143 Sonidegib small molecule approved 956697-53-3 485.507 C26H26F3N3O3 Q99835#Smoothened homolog Sonidegib has been shown to inhibit a transmembrane protein called SMO which plays a role in Hh signal transduction. This has resulted in inhibition of Hh signaling as well as antitumour activity in various animal models. In a transgenic mouse model of islet cell neoplasms, tumour volume was reduce by 95% in mice treated with sonidegib when compared with untreated mice. (2) DB09144 Uridine triacetate small molecule approved 4105-38-8 370.314 C15H18N2O9 Not Available D0OL7F DB09145 Water small molecule approved 7732-18-5 18.0153 H2O Not Available DB09146 Iron sucrose small molecule approved 8047-67-4 866.546 C12H29Fe5Na2O23 Significant increases in serum iron and serum ferritin and significant decreases in total iron binding capacity occurred four weeks from the initiation of iron sucrose treatment. DB09148 Florbetaben (18F) small molecule approved 902143-01-5 358.444 C21H26FNO3 P05067#Amyloid beta A4 protein DB09149 Florbetapir (18F) small molecule approved 956103-76-7 359.432 C20H25FN2O3 P05067#Amyloid beta A4 protein Following intravenous injection, florbetapir F 18 diffuses across the human blood-brain barrier and produces a radioactivity signal detectable throughout the brain. Subsequently, cerebral perfusion decreases the brain florbetapir F 18 content, with differential retention of the drug in areas that contain β-amyloid aggregates compared to areas that lack the aggregates. DB09151 Flutemetamol (18F) small molecule approved 765922-62-1 273.32 C14H11FN2OS P05067#Amyloid beta A4 protein Following intravenous injection, flutemetamol F 18 diffuses across the human blood-brain barrier and produces a radioactivity signal detectable throughout the brain. Subsequently, cerebral perfusion decreases the brain flutemetamol F 18 content, with differential retention of the drug in cortical areas that contain β-amyloid aggregates compared to areas that lack the aggregates. DB09152 Nitrogen small molecule approved 7727-37-9 28.0134 N2 Boiling point of liquid nitrogen is -196°C, which is the responsible for creating the initial stage which is heat transfer. The second stage is cell injury which is induced during thawing conditions of the cells. The last step in the cryotherapy is the inflammation stage which is characterized by edema and erythema. Inflammation occurs as a result of cellular death and it helps in local cell destruction. DB09153 Sodium chloride small molecule approved 7647-14-5 58.443 ClNa Sodium, the major cation of the extracellular fluid, functions primarily in the control of water distribution, fluid balance, and osmotic pressure of body fluids. Sodium is also associated with chloride and bicarbonate in the regulation of the acid-base equilibrium of body fluid. D04YZL DB09154 Sodium citrate small molecule approved 68-04-2 258.068 C6H5Na3O7 Citrate prevents activation of the clotting cascade by chelating calcium ions. Citrate neutralizes acid in the stomach and urine, raising the pH 8. DB09155 Helium small molecule approved 7440-59-7 4.0026 He Helium increases the coronary collateral circulation and enhances the vasodilatory effects of inhaled nitric oxide on pulmonary vessels. It is suggested to possess neuroprotective properties. Cardioprotective effects against ischemia are mediated through early and late preconditioning by exposing the myocardial tissues to short ischemic episodes. Studies show that helium is associated with activation of pro-survival signalling kinases and inhibition of the opening of mitochondrial permeability transition pore (mPTP). DB09156 Iopromide small molecule approved 73334-07-3 791.1119 C18H24I3N3O8 Not Available D07GNP DB09157 Carbon dioxide small molecule approved 124-38-9 44.0095 CO2 Data not found. DB09158 Trypan blue free acid small molecule approved 2538-83-2 872.87 C34H28N6O14S4 Not Available DB09160 Technetium Tc-99m tetrofosmin small molecule approved 127455-27-0 898.86 C36H84O10P4Tc Preclinical studies have reported that technetium-99m tetrofosmin presents a very good heart uptake and retention. The diagnosis based on the presence of technetium-99m is considered to have a principal photon gamma emissions at 140.5 keV.3 The imaging can be done at 15 minutes after stress and 30-60 minutes at rest but, due to its slow wash out from myocardium, it is possible to perform imaging for up to 4 hours post-injection.4 Administration of technetium-99m tetrofosmin generates a count elevation in white blood cell at 6-24 hours post-injection.1 DB09161 Technetium Tc-99m sestamibi small molecule approved 109581-73-9 775.96 C36H66N6O6Tc Not Available DB09164 Technetium Tc-99m disofenin small molecule approved 449.321 C18H26N2O5Tc Radiopharmaceutical agent is delivered to liver sinusoids via the portal vein and hepatic artery to diffuse through the pores in the endothelial lining to bind to a specific membrane bound carrier, which transports the tracer across the hepatocyte membrane and into the hepatocyte 3. Once inside the hepatocyte, the tracer may be bound by various enzymes and/or undergo metabolism. DB09165 Technetium Tc-99m pyrophosphate small molecule approved 52997-54-3 272.847 O7P2Tc Technetium Tc-99m pyrophosphate collects in areas of altered osteogenesis and injured myocardium. It also has an affinity for red blood cells, enabling imaging of blood pools. DB09167 Dosulepin small molecule approved 113-53-1 295.44 C19H21NS P08908#5-hydroxytryptamine receptor 1A@P28223#5-hydroxytryptamine receptor 2A@P70174#Histamine H1 receptor@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5@P23975#Sodium-dependent noradrenaline transporter@P31645#Sodium-dependent serotonin transporter Dosulepin is a tricyclic antidepressant that interacts with various receptors and transporters. It is a monoamine reuptake inhibitor with approximately equal potency for noradrenaline and 5-HT that increases the availability of these neurotransmitters at the central synapses 8. The metabolites of dosulepin are shown to inhibit 5HT uptake by the human blood platelet 2. DB09183 Dasabuvir small molecule approved 1132935-63-7 493.58 C26H27N3O5S Dasabuvir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotype 1 Label. DB09185 Viloxazine small molecule approved 46817-91-8 237.299 C13H19NO3 P23975#Sodium-dependent noradrenaline transporter@P41595#5-hydroxytryptamine receptor 2B@P28335#5-hydroxytryptamine receptor 2C@P35368#Alpha-1B adrenergic receptor@P07550#Beta-2 adrenergic receptor@P70174#Histamine H1 receptor@P25021#Histamine H2 receptor@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P21397#Amine oxidase [flavin-containing] A@P27338#Amine oxidase [flavin-containing] B Viloxazine is a serotonin-norepinephrine modulating agent that has been used as a treatment for depression and Attention Deficit Hyperactivity Disorder (ADHD).6 Although it is not a stimulant agent, viloxazine produces amphetamine-like CNS stimulant effects without a risk for drug abuse or dependence.4 Viloxazine does not produce sedative anticholinergic or adrenergic effects.1,4 D0V9JR DB09195 Lorpiprazole small molecule approved 108785-69-9 405.469 C21H26F3N5 P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P70174#Histamine H1 receptor@P31645#Sodium-dependent serotonin transporter Drugs like lorpiprazole that fit in the category of serotonin antagonists and reuptake inhibitors present a wide variety of effects when administered. They inhibit serotonin receptors like 5-HT2A as well as prevent the reuptake of serotonin, norepinephrine and dopamine. Additionally, they antagonize some adrenergic receptors. This diverse functional profile allows lorpiprazole to have a large therapeutic spectrum from symptom control as an adjuvant of other drugs to control of depressive syndromes as a monotherapy.2 DB09205 Moxisylyte small molecule approved 54-32-0 279.38 C16H25NO3 P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Administration of moxisylyte has shown to improve peripheral flow in occlusive arterial disease with little effect in blood pressure. There are reports of increases in cutaneous blood flow and skin temperature after local application of moxisylyte.10 D0A7QN DB09209 Pholcodine small molecule approved 509-67-1 398.4953 C23H30N2O4 P35372#Mu-type opioid receptor@P41145#Kappa-type opioid receptor@P41143#Delta-type opioid receptor The therapeutic doses of pholcodine have been shown not to cause depression of respiration, CNS excitation or other side effects associated with narcotics. It is thought that the impact of pholcodine is selective on the cough center without affecting the respiratory center. Pholcodine is not euphorigenic, and thus, psychological dependence is unlikely. Clinical trials have not shown any evidence of addiction after prolonged administration of pholcodine.6 It is well reported that pholcodine presents a more considerable respiratory depression effect than codeine and it causes hypotension in the same degree than codeine. Some other noted impacts of pholcodine in preclinical trials are: 1) the induction of histamine release, 2) anti-histaminic effect, 3) anti-acetylcholinic action, 4) anti-convulsant action and 5) mild tranquilizing action.7 DB09210 Piracetam small molecule approved 7491-74-9 142.1558 C6H10N2O2 Piracetam is known to mediate various pharmacodynamic actions: D0Q4YK DB09212 Loxoprofen small molecule approved 68767-14-6 246.3016 C15H18O3 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Loxoprofen is a non-selective inhibitor of cyclooxygenase enzymes, which are responsible for the formation of various biologically active pain, fever, and inflammatory mediators. These include prostaglandins, prostacyclin, thromboxane, and arachidonic acid.7,8 DB09213 Dexibuprofen small molecule approved 51146-56-6 206.2808 C13H18O2 Q07869#Peroxisome proliferator-activated receptor alpha@P37231#Peroxisome proliferator-activated receptor gamma@P10415#Apoptosis regulator Bcl-2@P35354#Prostaglandin G/H synthase 2@P07359#Platelet glycoprotein Ib alpha chain@P00750#Tissue-type plasminogen activator@P07204#Thrombomodulin@P13569#Cystic fibrosis transmembrane conductance regulator@P12104#Fatty acid-binding protein, intestinal@P31151#Protein S100-A7 For more information, refer to ibuprofen. D06YPU DB09214 Dexketoprofen small molecule approved 22161-81-5 254.2806 C16H14O3 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 This drug is an isomer of ketoprofen. Dexketoprofen a propionic acid derivative with analgesic, anti-inflammatory, and antipyretic properties 3. DB09216 Tolfenamic acid small molecule approved 13710-19-5 261.704 C14H12ClNO2 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Studies have shown that tolfenamic acid presents a non-dose dependent partial inhibition of irritant-induced temperature rise as well as a dose-dependent inhibition of skin edema. By studying its NSAID properties more closely, it was noted a dose-related inhibition of serum thromboxane which indicated the inhibition of COX-1. In the same line, there was noted a inhibition of prostaglandin E2 synthesis which marks a related COX-2 inhibition.3 The maximal inhibition of thromboxane was greater than 80% as well as is proven to be a potent prostaglandin E inhibitor.4 DB09219 Bisoxatin small molecule approved 17692-24-9 333.343 C20H15NO4 Bisoxatin is a stimulant laxative which increases peristalsis and inhibits the absorbtion of water and ions in the intestine 1. This increases the water content of the feces and increases its movement through the intestine. DB09220 Nicorandil small molecule approved 65141-46-0 211.177 C8H9N3O4 O60706#ATP-binding cassette sub-family C member 9 Nicorandil is a potassium channel opener with nitrovasodilator (NO donor) actions, making it both an arterial and a venous dilator 11. It causes sustained dilation of both the arterial resistance and conductive vessels that increases coronary blood flow, however the effect of the drug on coronary arteries does not involve the coronary steal phenomenon 12. Activation of potassium channels lead to hyperpolarization of the smooth muscle cells, followed by arterial dilation and afterload reduction. Nicorandil is shown to increase pooling in the capacitance vessels with a decrease in preload through relaxing the venous vascular system. Overall, improved blood flow and reduced infarct size are achieved through reduction of end-diastolix pressure and decreased extravascular component of vascular resistance 12. Open studies showed the effectiveness of nicorandil treatment on various types of angina pectoris 8. D0O2SR DB09225 Zotepine small molecule approved 26615-21-4 331.86 C18H18ClNOS P28223#5-hydroxytryptamine receptor 2A@P34969#5-hydroxytryptamine receptor 7@P23975#Sodium-dependent noradrenaline transporter@P31645#Sodium-dependent serotonin transporter@P50406#5-hydroxytryptamine receptor 6 In preclinical studies, zotepine is characterized by the presence of a strong antiserotonergic activity when compared with other neuroleptic drugs. It has also been reported to present elevations in the seizure threshold in the amygdaloid nucleus.1 When zotepine's effects were analyzed by electroencephalography, it was noted a typical response of a low-potency neuroleptics of the sedative type. Administration of zotepine has shown improvements in numerical movements and complex reaction. These effects tend to be accompanied by increases in pulse rate, increase in prolactin levels and some typical neuroleptic side effects.3,4 DB09236 Lacidipine small molecule approved 103890-78-4 455.551 C26H33NO6 Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A acidipine is a specific and potent calcium antagonist with a predominant selectivity for calcium channels in the vascular smooth muscle. Its main action is to dilate predominantly peripheral and coronary arteries, reducing peripheral vascular resistance and lowering blood pressure 6. DB09237 Levamlodipine small molecule approved 103129-82-4 408.88 C20H25ClN2O5 Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@P29474#Nitric oxide synthase, endothelial@P35228#Nitric oxide synthase, inducible Levamlodipine inhibits L-type calcium channels in vascular smooth muscle, reducing peripheral vascular resistance and blood pressure.8 It is given once daily in doses of 1.25-2.5mg in children and 2.5-5mg in adults.8 Patients should be counselled regarding the risk of symptomatic hypotension, worsening angina, and myocardial infarction.8 D0I2WV DB09238 Manidipine small molecule approved 89226-50-6 610.711 C35H38N4O6 Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A Manidipine produces vasodilation resulting in lower blood pressure 1. DB09241 Methylene blue small molecule approved 61-73-4 319.85 C16H18ClN3S P33402#Guanylate cyclase soluble subunit alpha-2@P29475#Nitric oxide synthase, brain Not Available D09NYS DB09242 Moxonidine small molecule approved 75438-57-2 241.677 C9H12ClN5O P08913#Alpha-2A adrenergic receptor@Q9Y2I1#Nischarin Antihypertensive agent whose site of action is the Central Nervous System (CNS), specifically involving interactions with I1- imidazoline and alpha-2-adrenergic rececptors within the rostral ventrolateral medulla (RSV). Label DB09256 Tegafur small molecule approved 17902-23-7 200.169 C8H9FN2O3 P04818#Thymidylate synthase Tegafur is an antineoplastic agent that belongs in the class of pyrimidine analogues. It interferes with the 2'-deoxythymidylate (DTMP) synthesis in the pyrimidine pathway, resulting in inhibition of DNA synthesis 4. In a phase III trial investigating the clinical efficacy of S-1 (tegafur/gimeracil/oteracil) in patients with advanced or recurrent gastric cancer, treatment resulted in a high response rate and was associated with a longer overall survival and longer progression-free survival rate when used in combination with cisplatin 1. In a meta analysis, triple combination therapy consisting of tegafur, gimeracil and oteracil showed longer survival times and well tolerance in patients with advanced gastric cancer 2. Tegafur and its active metabolites are potent myleosuppressive agents 5. D0F3SY DB09257 Gimeracil small molecule approved 103766-25-2 145.54 C5H4ClNO2 Not Available DB09265 Lixisenatide small molecule approved 320367-13-3 4858.56 C215H347N61O65S P43220#Glucagon-like peptide 1 receptor Lixisenatide acts as an agonist at the GLP-1 receptor. In the pancreas, this agonism results in increased glucose-stimulated insulin exocytosis by beta islet cells. This produces a reduction in blood glucose due to increased glucose uptake by tissues 1. GLP-1 receptor activation in the GI tract results in delayed gastric emptying which is thought to mediate the effects of lixisenatide on postprandial blood glucose. D05MKA DB09267 Strontium ranelate small molecule approved 135459-87-9 513.49 C12H6N2O8SSr2 In general, it is believed that strontium ranelate is capable of affecting a rebalance in bone turnover in favour of bone formation by: (1) increasing osteoblast differentiation from progenitors, osteoblast activity and survival, as well as regulating osteoblast-induced osteoclastogenesis, and (2) decreasing osteoclast differentiation and activity, as well as increasing osteoclast apoptosis 1. D0X7KZ DB09268 Picosulfuric acid small molecule approved 10040-34-3 437.44 C18H15NO8S2 electrolytes, and increases their secretion into the intestinal lumen 3. It is hydrolyzed by colonic bacterial enzyme, sulfatase 3, to form an active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM), which acts directly on the colonic mucosa to stimulate colonic peristalsis Label. DB09269 Phenylacetic acid small molecule approved 103-82-2 136.1479 C8H8O2 Not Available DB09270 Ubidecarenone small molecule approved 303-98-0 863.3435 C59H90O4 P56181#NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial@P31040#Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial Ubidecarenon has roles in many prysiological process including sulfide oxidation, regulation of mitochondrial permeability transition pore and translocation of protons and calcium ions accross biological membranes. Studies have shown its benefitial effect in treating cancer, statin myopathy, congestive heart failure and hypertension.2 DB09272 Eluxadoline small molecule approved 864821-90-9 569.662 C32H35N5O5 P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor D09ZXR DB09274 Artesunate small molecule approved 88495-63-0 384.425 C19H28O8 P04926#Malaria protein EXP-1 Artesunate is an artemisinin derivative that is metabolized to DHA, which generates free radicals to inhibit normal function of Plasmodium parasites.1,7,8 It has a short duration of action due to its short half life, and a moderate therapeutic index.7,8 Patients should be counselled regarding the risk of post treatment hemolytic anemia and hypersenstivity.8 D0D4JO DB09275 Bismuth subcitrate potassium small molecule approved 880149-29-1 780.654 C12H8BiK5O14 O25926#ATP-dependent Clp protease ATP-binding subunit ClpX Bismuth subcitrate is very effective in the treatment of gastroduodenal disorders and appears to act via several mechanisms. It has little acid-neutralizing effect and does not affect acid secretion. DB09276 Sodium aurothiomalate small molecule approved 12244-57-4 390.07 C4H3AuNa2O4S Unknown, may decrease prostaglandin synthesis or may alter cellular mechanisms by inhibiting sulfhydryl systems. DB09277 Choline C 11 small molecule approved 87591-54-6 138.62 C5H14ClNO Choline is phosphorylated by choline kinase into phosphorylcholine. This phosphorylated form gets trapped inside the cell. Cancer cells exhibit an increased cell wall membrane synthesis as well as an increased activity of choline kinase. Choline C11 presents a small tracer activity in the urinary collecting system and this property makes it a very noble compound in the evaluation of ureters and bladder.3 DB09278 Activated charcoal small molecule approved 64365-11-3 12.011 C Activated charcoal may also have an effect on systemic drug levels by lowering the serum levels of already absorbed drugs or toxins. Many absorbed drugs that undergo significant hepatic metabolism and conjugation are eliminated via bile into the small intestines. When they reach the small intestines, drug conjugates can undergo hydrolysis and return to the enterohepatic circulation. Activated charcoal interferes with this process and binds to the conjugated drug before hydrolysis or the free deconjugated drug before reabsorption. DB09280 Lumacaftor small molecule approved 936727-05-8 452.414 C24H18F2N2O5 P13569#Cystic fibrosis transmembrane conductance regulator Results from clinical trials indicated that treatment with Orkambi (lumacaftor/ Ivacaftor) results in improved lung function, reduced chance of experiencing a pulmonary exacerbation, reduced sweat chloride, increased weight gain, and improvements in CF symptoms and quality of life.Label D0X0CB DB09281 Magnesium trisilicate small molecule approved 14987-04-3 260.857 Mg2O8Si3 Magnesium trisilicate works by increasing the pH of gastric juice via a neutralisation reaction. It also precipitates colloidal silica, which can coat gastrointestinal mucosa conferring further protection. DB09282 Molsidomine small molecule approved 25717-80-0 242.235 C9H14N4O4 P33402#Guanylate cyclase soluble subunit alpha-2 Molsidomine leads to smooth muscle relaxation in the coronary blood vessels, relieving symptoms of angina and increasing blood flow to the coronary arteries. D08VXL DB09291 Rolapitant small molecule approved 552292-08-7 500.485 C25H26F6N2O2 P25103#Substance-P receptor Not Available D0CF0Y DB09292 Sacubitril small molecule approved 149709-62-6 411.498 C24H29NO5 P08473#Neprilysin n a 7-day valsartan-controlled study in patients with reduced ejection fraction (HFrEF), administration of sacubitril + valsartan (Entresto) resulted in a significant non-sustained increase in natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP compared to valsartan. In a 21-day study in HFrEF patients, it significantly increased urine ANP and cGMP and plasma cGMP, and decreased plasma NT-proBNP, aldosterone and endothelin-1. In clinical studies, this combination had no effect on QTc interval. DB09293 Iodide I-131 small molecule approved 14914-30-8 130.9067 I The therapeutic effects of sodium iodide I-131 are a result of the ionizing radiation absorbed by the thyroidal tissue. Tissue damage is the result of direct insult to molecules by ionization and excitation and the consequent dissociation of those molecules. About 90% of local irradiation from sodium iodide I-131 is the result of beta radiation and 10% is the result of gamma radiation. DB09296 Ombitasvir small molecule approved 1258226-87-7 894.127 C50H67N7O8 Q5L478#Nonstructural protein 5A Ombitasvir is classified as a direct acting antiviral and acts against HCV to inhibit viral replication Label. DB09297 Paritaprevir small molecule approved 1216941-48-8 765.89 C40H43N7O7S At concentrations approximately 6 and 1.8 times the therapeutic concentrations of paritaprevir and ombitasvir, the combination did not prolong QTc to any clinically relevant extent Label. DB09299 Tenofovir alafenamide small molecule approved 379270-37-8 476.474 C21H29N6O5P Q72547#Reverse transcriptase/RNaseH@Q3MS49#Reverse transcriptase Tenofovir alafenamide has been shown to be a potent inhibitor of hepatitis B viral replication.4 DB09300 Butylscopolamine small molecule approved 7182-53-8 360.473 C21H30NO4 P20309#Muscarinic acetylcholine receptor M3@P08172#Muscarinic acetylcholine receptor M2 Scopolamine butylbromide is a muscarinic antagonist which acts to prevent acetylcholine-stimulated contraction of smooth muscle in the gastrointestinal tract 1. D05EMG DB09313 Ioxaglic acid small molecule approved 59017-64-0 1268.886 C24H21I6N5O8 This drug allows for the visualization of important organs and structures in the body. It binds to tissues, allowing the blockage of X-rays and diagnostic visualization in various soft tissues and body cavities 8. DB09314 Technetium Tc-99m pertechnetate small molecule approved 23288-61-1 169.968 H8O4Tc DB09315 Xenon-133 small molecule approved 14932-42-4 132.9059 Xe Xenon Xe 133 is a readily diffusible gas which is neither utilized nor produced by the body. It passes through cell membranes and freely exchanges between blood and tissue. It tends to concentrate more in body fat than in blood, plasma, water or protein solutions. DB09316 Thallous Chloride small molecule approved 7791-12-0 239.836 ClTl Data not found. DB09319 Carindacillin small molecule approved 35531-88-5 494.56 C26H26N2O6S P0AEB2#D-alanyl-D-alanine carboxypeptidase DacA@P24228#D-alanyl-D-alanine carboxypeptidase DacB@P08506#D-alanyl-D-alanine carboxypeptidase DacC@P02919#Penicillin-binding protein 1B Not Available DB09320 Procaine benzylpenicillin small molecule approved 54-35-3 570.71 C29H38N4O6S It is an antibiotic against penicillin-susceptible microorganisms with bactericidal effect. Like all penicillins, procaine benzylpenicillin interferes with the synthesis of the bacterial cell wall peptidoglycan. It acts through the inhibition of biosynthesis of cell-wall peptidoglycan, rendering the cell wall osmotically unstable. It is part of the penicillin and beta lactam family of antibacterial drugs. DB09321 Zinc oxide small molecule approved 1314-13-2 81.408 OZn Zinc oxide has astringent, soothing and protective properties and is used in topical preparations for eczema, slight excoriations, wounds and haemorrhoids. It also reflects ultraviolet radiation and can be used as a physical sunscreen. DB09322 Zinc sulfate small molecule approved 7733-02-0 161.472 O4SZn Zinc has been identified as a cofactor for over 70 different enzymes, including alkaline phosphatase, lactic dehydrogenase and both RNA and DNA polymerase. Zinc facilitates wound healing, helps maintain normal growth rates, normal skin hydration and the senses of taste and smell. DB09324 Sulbactam small molecule approved 68373-14-8 233.242 C8H11NO5S Q93LQ9#Beta-lactamase Not Available DB09325 Sodium fluoride small molecule approved 7681-49-4 41.9882 FNa Sodium fluoride protects the teeth from acid demineralization while preventing tooth decay by bacteria while strengthening tooth enamel.2,6 It is important to note that excess fluoride exposure during tooth mineralization, especially in children 1-3 years old, may cause fluorosis. It is a condition manifested by white lines, pitting, or discoloration of teeth resulting from changes in tooth enamel.8,18 The risk of fluorosis can be decreased by the use of a rice-size amount of fluoridated toothpaste in children younger than 3 years old. It is recommended that no more than a pea-sized quantity of fluoridated toothpaste should be used for children from 3 to 6 years old.18 The American Dentistry Association (ADA) recommends that children should be closely supervised during toothpaste use to prevent excess fluoride ingestion.19 DB09326 Ammonia N-13 small molecule approved 34819-78-8 16.03 H3N Following intravenous injection, ammonia N 13 enters the myocardium through the coronary arteries. The PET technique measures myocardial blood flow based on the assumption of a three-compartmental disposition of intravenous ammonia N 13 in the myocardium. In this model, the value of the rate constant, which represents the delivery of blood to myocardium, and the fraction of ammonia N 13 extracted into the myocardial cells, is a measure of myocardial blood flow. Optimal PET imaging of the myocardium is generally achieved between 10 to 20 minutes after administration. DB09327 Tegafur-uracil small molecule approved 74578-38-4 312.257 C12H13FN4O5 P04818#Thymidylate synthase The use of the combination of tegafur and uracil allows increasing the oral bioavailability, improving the pharmacokinetic behavior of the delivered 5-fluoruracil and increasing the half-life of tegafur. The effect of this combo drug can ameliorate the usage by reducing the dosage frequency which tends to be uncomfortable for the patients.4 The effect of tegafur's metabolites results in a decreased thymidine synthesis, DNA synthesis, disrupted RNA function and tumor cell cytotoxicity.9 DB09330 Osimertinib small molecule approved 1421373-65-0 499.619 C28H33N7O2 P00533#Epidermal growth factor receptor A pharmacokinetic/pharmacodynamic analysis suggested a concentration-dependent QTc interval prolongation of 14 msec (upper bound of two-sided 90% CI: 16 msec) at a dose of osimertinib 80 mg. D0O8GK DB09332 Kappadione small molecule approved 131-13-5 422.084 C11H8Na4O8P2 P00734#Prothrombin@P08709#Coagulation factor VII@P00740#Coagulation factor IX@P00742#Coagulation factor X@P04070#Vitamin K-dependent protein C@P38435#Vitamin K-dependent gamma-carboxylase@P07225#Vitamin K-dependent protein S Menadiol sodium diphosphate is a highly water-soluble vitamin K analog. The presence of vitamin K is necessary for the formation of prothrombin, factor VII, factor IX and factor X. Lack of vitamin K results in an increased risk of hemorrhage, which can be minor or life-threatening 10. DB09333 Iopodic acid small molecule approved 5587-89-3 597.961 C12H13I3N2O2 P55073#Thyroxine 5-deiodinase The thyroid effects of iopodic acid are related to the blocking of the more potent form of the thyroid hormone. It also blocks thyroid hormone release and it can interfere with its synthesis in some patients. The effects of iopopdic acid on some diseases, such as Graves disease, have been shown not to be as effective and to present a relapse after discontinuation.2,3 The effects of iopodic acid on thyroid has been proven to produce an inactivation of approximately 80% of the type II deiodinase in pituitary and cerebral cortex.4 DB09335 Alatrofloxacin small molecule approved 146961-76-4 558.518 C26H25F3N6O5 Not Available DB09340 Tyropanoic acid small molecule approved 27293-82-9 641.026 C15H18I3NO3 Tyropanoate sodium, also known as sodium tyropanoate, is a radiocontrast agent used in cholecystography (X-ray imagining and diagnosis of gallstones). This molecule contains three heavy iodine atoms which obstruct X-rays to produce a visible image. After injection, it is rapidly excreted into the bile 8,9,10. DB09342 Propoxycaine small molecule approved 86-43-1 294.395 C16H26N2O3 Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha Propoxycaine is a local anesthetic which acts to decrease nerve impulses and therefore pain sensation during dental procedures 4,5,6. D0N6CR DB09343 Tipiracil small molecule approved 183204-74-2 242.662 C9H11ClN4O2 P19971#Thymidine phosphorylase Tipiracil prevents trifluridine conversion into 5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione, which is an inactive major metabolite, by inhibiting the enzyme thymidine phosphorylase. Thus, tipiracil is able to increase trifluridine bioavailability. On the other hand, thymidine phsophorylase is a known platelet-derived endothelial cell growth factor and its inhibition generates an indirect antiangiogenic benefit.3 DB09345 Pramocaine small molecule approved 140-65-8 293.407 C17H27NO3 Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha Pramocaine temporarily relieves pain, pruritis, burning and discomfort associated with minor lip and skin irritations and hemorrhoid's by inhibiting voltage gated sodium channels on neurons. DB09346 Metrizoic acid small molecule approved 1949-45-7 627.943 C12H11I3N2O4 Not Available DB09348 Propiolactone small molecule approved 57-57-8 72.063 C3H4O2 When employed under conditions of maximum effectiveness, propiolactone is approximately 25 more active as a vapor phase disinfectant than formaldehyde, 4000 times more active than ethylene oxide and 50000 times more active than methyl bromide.6 It has been shown to be mutagenic by inducing cell transformation, chromosomal aberrations and chromatoid exchange. Propiolactone has been shown to be mutagenic in both somatic and germ cells.7 D0Z8AA DB09350 Piperonyl butoxide small molecule approved 51-03-6 338.4385 C19H30O5 Piperonyl butoxide does not affect the mixed-function oxidase system in humans. In small trials in human volunteers, usual doses of piperonyl butoxide had no effect on humans. DB09351 Levobetaxolol small molecule approved 93221-48-8 307.434 C18H29NO3 P08588#Beta-1 adrenergic receptor Levobetaxolol is a selective β1 adrenergic receptor antagonist Label. It acts to lower intraocular pressure. Levobataxolol is condsidered to be the more active component of the betaxolol racemate. D0A6CQ DB09352 Hydroxyamphetamine small molecule approved 103-86-6 151.2056 C9H13NO Not Available DB09353 Octasulfur small molecule approved 10544-50-0 256.52 S8 Sulfur is converted to hydrogen sulfide (H2S) through reduction, partly by bacteria. H2S has a lethal action on bacteria (possibly including Propionibacterium acnes) which plays a role in acne, fungi, and parasites such as scabies mites. DB09355 Sulfabenzamide small molecule approved 127-71-9 276.311 C13H12N2O3S Not Available DB09357 Dexpanthenol small molecule approved 81-13-0 205.2515 C9H19NO4 Pantothenic acid is a precursor of coenzyme A, which serves as a cofactor for a variety of enzyme-catalyzed reactions involving transfer of acetyl groups. The final step in the synthesis of acetylcholine consists of the choline acetylase transfer of acetyl group from acetylcoenzyme A to choline. Acetylcholine is the neurohumoral transmitter in the parasympathetic system and as such maintains the normal functions of the intestine. Decrease in acetylcholine content would result in decreased peristalsis and in extreme cases adynamic ileus. D0H9ZQ DB09364 Procaine merethoxylline small molecule approved 60064-28-0 764.24 C28H41HgN3O9 Not Available DB09366 Propyliodone small molecule approved 587-61-1 447.011 C10H11I2NO3 Not Available D0NU2H DB09370 Sodium phosphate P 32 small molecule approved 7635-46-3 142.957 HNa2O4P Not Available D0I6JF DB09371 Norethynodrel small molecule approved 68-23-5 298.426 C20H26O2 P03372#Estrogen receptor@P10275#Androgen receptor@P04278#Sex hormone-binding globulin Not Available DB09372 Tannic acid small molecule approved 1401-55-4 1701.206 C76H52O46 Not Available DB09374 Indocyanine green acid form small molecule approved 28782-33-4 753.99 C43H49N2O6S2 Not Available DB09376 Lapyrium small molecule approved 109260-82-4 363.521 C21H35N2O3 Lapyrium is a quaternary ammonium cation (QAC). QACs exert broad spectrum antimicrobial activity, acting as bactericidal agents 2. DB09377 Undecoylium chloride iodine complex small molecule approved 1338-54-1 272.73 C12H17ClN2O3 Not Available DB09378 Fluprednisolone small molecule approved 53-34-9 378.44 C21H27FO5 Not Available D0V9DZ DB09380 Sodium chromate Cr-51 small molecule approved 10039-53-9 160.92 CrNa2O4 Not Available DB09382 Iodohippurate sodium I-131 small molecule approved 881-17-4 331.055 C9H7INNaO3 Not Available DB09383 Meprednisone small molecule approved 1247-42-3 372.461 C22H28O5 Not Available D0I5DS DB09385 Cyanocobalamin Co-57 small molecule approved 13115-03-2 1354.399 C63H89CoN14O14P Not Available DB09389 Norgestrel small molecule approved 6533-00-2 312.453 C21H28O2 P06401#Progesterone receptor@P18405#3-oxo-5-alpha-steroid 4-dehydrogenase 1@P10275#Androgen receptor Not Available DB09394 Phosphoric acid small molecule approved 7664-38-2 97.9952 H3O4P Transport of phosphate from the gut lumen is an active, energy-dependent process that is modified by several factors. ... Vitamin D stimulates phosphate absorption, an effect reported to precede its action on calcium ion transport. DB09395 Sodium acetate small molecule approved 127-09-3 82.0338 C2H3NaO2 Sodium is the principal cation of extracellular fluid. It comprises more than 90% of total cations at its normal plasma concentration of approximately 140 mEq/liter. The sodium ion exerts a primary role in controlling total body water and its distribution. Acetate ions acts as hydrogen ion acceptor which is alternative to bicarbonate. DB09397 Technetium Tc-99m sulfur colloid small molecule approved 355.39 S8Tc Not Available DB09398 Fluoride ion F-18 small molecule approved 67862-54-8 18.0015 F Deposition of 18F fluoride in bone appears to be primarily a function of blood flow to the bone and the efficiency of the bone in extracting the 18F from the blood perfusing the bone. Increased fluorine F 18 ion deposition around joints can occur in arthritis or following trauma; increased deposition has also been documented in bone around fracture sites, in osteomyelities, fibrous dysplasia, spondylitis tuberculosa, Paget's disease, hyperstosis frontalis interna, myositis, ossificans, and in rapidly growing epiphyses. The tendency for fluorine F 18 ions to accumulate in the vicinity of primary and metastatic malignancy in bone has proven clinically useful in detection of such lesions DB09400 Selenomethionine Se-75 small molecule approved 1187-56-0 192.071 C5H11NO2Se Not Available D01OPV DB09401 Isosorbide small molecule approved 652-67-5 146.1412 C6H10O4 Q02108#Guanylate cyclase soluble subunit alpha-1@Q02153#Guanylate cyclase soluble subunit beta-1 Isosorbide reduces intraocular pressure through its effects on ocular blood vessels.8,12 While in the blood, isosorbide promotes redistribution of water toward the circulation, promoting the excretion of urine.12 DB09403 Iocetamic acid small molecule approved 16034-77-8 613.96 C12H13I3N2O3 Not Available D0P5CD DB09407 Magnesium chloride small molecule approved 7786-30-3 95.211 Cl2Mg The oral administration of a single 800 mg dose of magnesium chloride in healthy volunteers resulted in a diminished rate of intraluminal lipid and protein digestion. The most pronounced effect of magnesium chloride, however, was a decreased gastric emptying rate of both test meals. After correction for gastric emptying, no differences were noted in intraluminal lipid or protein digestion. Therefore, the lower lipid levels noted after magnesium supplementation are unlikely to be the result of altered lipid assimilation. Magnesium chloride slows gastric emptying but does not influence lipid digestion. DB09409 Magnesium acetate tetrahydrate small molecule approved 16674-78-5 214.453 C4H14MgO8 Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B DB09413 Monopotassium phosphate small molecule approved 7778-77-0 136.0855 H2KO4P Potassium is the major cation of intracellular fluid and is essential for maintenance of acid-base balance, isotonicity, and electrodynamic characteristics of the cell. Potassium is an important activator in many enzymatic reactions and is essential to a number of physiologic processes including transmission of nerve impulses; contraction of cardiac, smooth, and skeletal muscles; gastric secretion; renal function; tissue synthesis; and carbohydrate metabolism. DB09414 Dipotassium phosphate small molecule approved 7758-11-4 174.1759 HK2O4P Phosphate is a major intracellular anion which participates in providing energy for metabolism of substances and contributes to important metabolic and enzymatic reactions in almost all organs and tissues. Phosphate exerts a modifying influence on calcium concentrations, a buffering effect on acid-base equilibrium, and has a major role in the renal excretion of hydrogen ions. DB09418 Potassium perchlorate small molecule approved 7778-74-7 138.549 ClKO4 Q92911#Sodium/iodide cotransporter Potassium perchlorate inhibits thyroid iodide transport. The clinical use of potassium perchlorate in hyperthyroidism, such as Graves' disease and amiodarone-induced hypothyroidism, have been investigated in various studies. Thyroid dysfunction occurs in about 15-20% of the patients receiving long-term amiodarone therapy 2. In patients with amiodarone-induced hypothyroidism, short-term administration of potassium perchlorate resulted in restoration of euthyroidism in most patients 4. Euthyroidism promoted by potassium perchlorate does not persist unless amiodarone treatment is withdrawn 2. DB09419 Xylose small molecule approved 58-86-6 150.1299 C5H10O5 Xylose is often used as a parent sugar alcohol from which the commonly used food additive sweetener, xylitol, can be derived via the hydrogenation of xylose. Xylitol possesses many characteristics that make it a healthy and effective alternative to regular sugar. For example, although it looks and tastes exactly like ordinary sugar 1, having a 100% relative sweetness versus normal sucrose 7, it also has a low impact on blood sugar and insulin secretion and a minimal caloric value of 2.4 calories/gm 7,1. Furthermore, xylitol is non-fermentable and thus cannot be transformed to acids by oral bacteria, allowing it to restore a proper alkaline/acid balance in the mouth 1. Various studies cite this effect for allowing xylitol products like chewing gum to be effective at reducing dental caries 1. Altogether, these characteristics make xylose and its xylitol metabolite an effective alternative sweetener for healthy food choices for individuals who may be diabetic or for individuals simply wanting to make healthy dietary choices for their bodies. D07HZY DB09420 Iodide I-123 small molecule approved 69239-56-1 122.9061 I Not Available DB09421 Protirelin small molecule approved 24305-27-9 362.3837 C16H22N6O4 Not Available DB09425 Indium In-111 pentetate small molecule approved 135998-32-2 501.23 C14H20InN3O10 Not Available DB09443 Krypton Kr 81m small molecule approved 15678-91-8 80.9166 Kr Not Available DB09449 Sodium phosphate, monobasic small molecule approved 7558-80-7 119.977 H2NaO4P Sodium phosphate inceases fecal water content to increase mobility through the large intestine 1. DB09460 Sodium carbonate small molecule approved 497-19-8 105.9884 CNa2O3 P00915#Carbonic anhydrase 1@P00918#Carbonic anhydrase 2@P22748#Carbonic anhydrase 4@Q16790#Carbonic anhydrase 9 Alkalizing buffering action: Sodium bicarbonate is an alkalinizing agent that dissociates to provide bicarbonate ion. Bicarbonate in excess of that needed to buffer hydrogen ions causes systemic alkalinization and, when excreted, urine alkalinization as well. DB09461 Xenon Xe-127 small molecule approved 13994-19-9 126.9052 Xe Not Available D02AEW DB09462 Glycerin small molecule approved 56-81-5 92.0938 C3H8O3 Q03181#Peroxisome proliferator-activated receptor delta@Q9NZK7#Group IIE secretory phospholipase A2@Q9NPH2#Inositol-3-phosphate synthase 1@P00325#Alcohol dehydrogenase 1B@Q14643#Inositol 1,4,5-trisphosphate receptor type 1@P09466#Glycodelin@P17050#Alpha-N-acetylgalactosaminidase@P84077#ADP-ribosylation factor 1@O43252#Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase 1@O43708#Maleylacetoacetate isomerase Glycerin is commonly classified as an osmotic laxative but may act additionally or alternatively through its local irritant effects; it may also have lubricating and fecal softening actions. Glycerin suppositories usually work within 15 to 30 minutes. DB09472 Sodium sulfate small molecule approved 7757-82-6 142.042 Na2O4S P00918#Carbonic anhydrase 2@P00915#Carbonic anhydrase 1 Induces catharsis by the osmotic effects of the unabsorbed sulfate salts and polyethylene glycol (PEG) in the GI tract. Specifically, sulfate salts provide sulfate anions, which are poorly absorbed, and PEG, which is primarily unabsorbed, causes water to be retained in the GI tract resulting in watery diarrhea. DB09473 Indium In-111 oxyquinoline small molecule approved 65389-08-4 543.364 C27H18InN3O3 Not Available DB09477 Enalaprilat small molecule approved 76420-72-9 348.3936 C18H24N2O5 P12821#Angiotensin-converting enzyme@P46663#B1 bradykinin receptor Enalaprilat injection results in the reduction of both supine and standing systolic and diastolic blood pressure, usually with no orthostatic component. Symptomatic postural hypotension is therefore infrequent, although it might be anticipated in volume-depleted patients. The onset of action usually occurs within fifteen minutes of administration with the maximum effect occurring within one to four hours. The abrupt withdrawal of enalaprilat has not been associated with a rapid increase in blood pressure. D0N5HJ DB09479 Rubidium Rb-82 small molecule approved 81.9177 Rb In human studies, myocardial activity was noted within the first minute after peripheral intravenous injection of Rb-82. When areas of infarction or ischemia are present in the myocardium, they are visualized within 2-7 minutes after injection as photon-deficient, or “cold”, areas on the myocardial scan. DB09480 Iofetamine I-123 small molecule approved 75917-92-9 299.189 C12H18IN Not Available DB09481 Magnesium carbonate small molecule approved 546-93-0 84.314 CMgO3 Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B Neutralizes acid in the stomach 5. DB09483 Potassium lactate small molecule approved 996-31-6 128.1683 C3H5KO3 Not Available DB09484 Sodium fluorophosphate small molecule approved 10163-15-2 143.949 FNa2O3P Not Available DB09487 Iotrolan small molecule approved 79770-24-4 1626.242 C37H48I6N6O18 Not Available D0B8LN DB09488 Acrivastine small molecule approved 87848-99-5 348.4382 C22H24N2O2 P70174#Histamine H1 receptor Not Available D0O4EU DB09490 Indium In-111 chloride small molecule approved 50800-85-6 217.26 Cl3In Indium In-111 Chloride is a radioactive tracer for labeling monoclonal antibodies in certain preparations such as OncoScint, ProstaScint and Zevalin. Its pharmacodynamics is related to the final product and not specific to Indium In-111 Chloride alone DB09494 Cetyl alcohol small molecule approved 36653-82-4 242.4406 C16H34O Cetyl alcohol exhibits skin protect properties against skin irritations caused by bites, rashes and stings. The inhibitory action of cetyl alcohol against the growth of Mycoplasma gallisepticum and Mycopiasma pneumoniae has been reported 1. DB09495 Avobenzone small molecule approved 70356-09-1 310.393 C20H22O3 Diminish the penetration of ultraviolet (UV) light through the epidermis by absorbing UV radiation within a specific wavelength range. The amount and wavelength of UV radiation absorbed are affected by the molecular structure of the sunscreen agent. DB09496 Octinoxate small molecule approved 5466-77-3 290.3972 C18H26O3 Acts as a photoprotective agent that protects the skin by preventing and minimizing the damaging effects of ultraviolet (UV) rays of natural light. The cellular effects of UV irradiation include DNA damage, cell cycle arrest, immunological depression, apoptosis, and transcriptional changes 7. DB09498 Strontium chloride Sr-89 small molecule approved 38270-90-5 159.81 Cl2Sr Metastatic bone lesions are zones of high bone mineral turnover. Thus, there is a constant need of calcium supply for the development of the malignancy. Strontium chloride 89 is a divalent ion, similar to calcium, therefore it is taken up by sites of active osteogenesis. This relieves bone metastatic-driven pain withouth generating important side effects and it also presents a very little radioprotection concern.10 Once combined with external beam radiotherapy, strontium chloride 89 can emit β particules with a maximum range in tissue of 6-8mm. This radiation is capable to reduce new bone metastases and produces an analgesic role.11 DB09499 Thiosulfuric acid small molecule approved 13686-28-7 114.144 H2O3S2 DB09501 Ferric ammonium citrate small molecule approved 1185-57-5 264.997 C6H11FeNO7 Not Available DB09502 Fludeoxyglucose (18F) small molecule approved 63503-12-8 181.15 C6H11FO5 In comparison to background activity of the specific organ or tissue type, regions of decreased or absent uptake of Fludeoxyglucose F 18 reflect the decrease or absence of glucose metabolism. Regions of increased uptake of Fludeoxyglucose F 18 reflect greater than normal rates of glucose metabolism. DB09510 Urea C-13 small molecule approved 58069-82-2 61.048 CH4N2O Q8KT33#Urease Not Available DB09512 Simethicone small molecule approved 8050-81-5 238.461 C6H18O4Si3 Simethicone decreases the surface tension of gas bubbles in the gastrointestinal tract, facilitating their expulsion.2 It has a short duration of action as it is generally given as needed, and a wide therapeutic index as it is not systemically absorbed.2 D01XRP DB09513 Urea C-14 small molecule approved 594-05-8 62.048 CH4N2O Q8KT33#Urease Not Available DB09516 Mequinol small molecule approved 150-76-5 124.1372 C7H8O2 Mequinol is in fact considered a melanocytotoxic chemical which when oxidized in melanocytes results in the formation of toxic entities like quinones 3. Such cytotoxic compounds subsequently have the potential to damage and destroy pigment cells, therefore causing skin depigmentation 3. In response, skin cells are naturally capable of protecting themselves against such cytotoxic agents with the help of endogenous intracellular glutathione and the detoxification action of glutathione S-transferase on the cytotoxic compounds 3. Regardless, it is consequently by way of this seemingly negative and damaging pharmacodynamic profile by which the mechanism of action of mequinol is sometimes described 3. DB09517 Sodium ferric gluconate complex small molecule approved 34089-81-1 2089.309 C66H121Fe2NaO65 P02792#Ferritin light chain@P68871#Hemoglobin subunit beta@P69905#Hemoglobin subunit alpha Sodium ferric gluconate complex is an exogenous epoetin that acts to restore the body's content of iron, which is essential for normal hemoglobin synthesis, oxygen transport, and enzymatic processes. The complex increases red blood cell production and increased iron utilization. D0VM8K DB09526 Hydroquinone small molecule approved 123-31-9 110.1106 C6H6O2 P14679#Tyrosinase@Q9Y271#Cysteinyl leukotriene receptor 1 Not Available D03UOT DB09531 Perflexane small molecule approved 355-42-0 338.044 C6F14 Not Available DB09534 Ecamsule small molecule approved 92761-26-7 562.69 C28H34O8S2 When exposed to UV ecamsule undergoes reversible photoisomerization followed by photoexcitation. The absorbed UV is then released as thermal energy, without penetrating the skin, thereby protecting the skin from UV exposure. DB09536 Titanium dioxide small molecule approved 13463-67-7 79.865 O2Ti Q9UEW3#Macrophage receptor MARCO Not Available DB09543 Methyl salicylate small molecule approved 119-36-8 152.1473 C8H8O3 Methyl salicylate relieve musculoskeletal pain in the muscles, joints, and tendons by causing irritation and reddening of the skin due to dilated capillaries and increased blood flow. It is pharmacologically similar to aspirin and other NSAIDs but as a topical agent it primarily acts as a rubefacient and skin irritant. Counter-irritation is believed to cause a soothing sensation of warmth. DB09546 Iobenguane sulfate I-123 small molecule approved 80663-95-2 640.26 C16H22I2N6O4S Iobenguane I-123 is taken up by and stored in adrenergic nerve terminals allowing for the radiographic imaging of adrenergically inervated organs and tissues [FDA Label]. DB09552 Thonzonium small molecule approved 25466-36-8 511.818 C32H55N4O P21283#V-type proton ATPase subunit C 1 Thonzonium bromide causes dispersion and penetration of cellular debris and exudate, thereby promoting tissue contact of the active ingredients contained in the administered medication. It is an inhibitor of vacuolar ATPase that uncouples and blocks the function of the pump without inhibiting ATP hydrolysis. DB09555 Dexchlorpheniramine maleate small molecule approved 2438-32-6 390.86 C20H23ClN2O4 P70174#Histamine H1 receptor In allergic reactions, an allergen binds to IgE antibodies on mast cells and basophils. Once this occurs IgE receptors crosslink with each other triggering a series of events that eventually leads to cell-degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritis, vasodilatation, hypotension, flushing, headache, tachycardia, and bronchoconstriction. Histamine also increases vascular permeability and potentiates pain. Dexchlorpheniramine, is a histamine H1 antagonist of the alkylamine class. It competes with histamine for the normal H1-receptor sites on effector cells of the gastrointestinal tract, blood vessels and respiratory tract. It provides effective, temporary relief of sneezing, watery and itchy eyes, and runny nose due to hay fever and other upper respiratory allergies. DB09561 Sodium glycerophosphate small molecule approved 1334-74-3 216.036 C3H7Na2O6P Glycerophosphate acts as a source of inorganic phosphate through hydrolysis 1. DB09563 Choline C-11 small molecule approved 94793-58-5 103.173 C5H14NO In a study of men with prostatic hyperplasia or primary prostate cancer, PET imaging showed 11C-choline radioactivity accumulated rapidly within the prostate; uptake appeared to peak by five minutes following injection of the drug and activity was retained over the subsequent 30 minute scanning period. Little uptake was observed in the bladder and rectum. D0C1QZ DB09570 Ixazomib small molecule approved 1072833-77-2 361.03 C14H19BCl2N2O4 In vitro studies have shown ixazomib to induce apoptosis in multiple myeloma cells sensitive or resistant to other conventional therapies. In mouse xenograft models, ixazomib induced tumor growth inhibition. D0Y2SW DB09571 Levmetamfetamine small molecule approved 33817-09-3 149.237 C10H15N Levomethamphetamine increases norepinephrine release resulting in increased vasocontriction. DB00918 Almotriptan small molecule approved 154323-57-6 335.464 C17H25N3O2S P28221#5-hydroxytryptamine receptor 1D@P28222#5-hydroxytryptamine receptor 1B Almotriptan is a selective 5-hydroxytryptamine receptor subtype agonist indicated for the acute treatment of migraine attacks with or without aura in adults. Almotriptan is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. Almotriptan is an agonist for a vascular 5-hydroxytryptamine receptor subtype (probably a member of the 5-HT1D family) having only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Almotriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Almotriptan in humans. DB00919 Spectinomycin small molecule approved 1695-77-8 332.3496 C14H24N2O7 P0A7S3#30S ribosomal protein S12 Spectinomycin is an aminocyclitol antibiotic produced by a species of soil microorganism designated as Streptomyces spectabilis. In vitro studies have shown spectinomycin to be active against most strains of Neisseria gonorrhoeae (minimum inhibitory concentration <7.5 to 20 mcg/mL). Footprint studies indicate that spectinomycin exerts regional effects on ribosomal structure. D02PCR DB00920 Ketotifen small molecule approved 34580-13-7 309.425 C19H19NOS P70174#Histamine H1 receptor@P52209#6-phosphogluconate dehydrogenase, decarboxylating Ketotifen is a non-competitive histamine antagonist and mast cell stabilizer.6 Administered orally, it functions as a non-bronchodilator antiasthmatic drug by inhibiting the effects of endogenous substances known to be inflammatory mediators.7 While effects can take 6 to 12 weeks to become apparent,5 the use of ketotifen has been demonstrated to reduce the frequency, severity, and duration of asthma symptoms, and may allow for a reduction in the use of other asthma therapies.7 D0YG7M DB00921 Buprenorphine small molecule approved 52485-79-7 467.6401 C29H41NO4 P41145#Kappa-type opioid receptor@P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@P41146#Nociceptin receptor Buprenorphine interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, buprenorphine exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Buprenorphine depresses the respiratory centers, depresses the cough reflex, and constricts the pupils. D06AWE DB00922 Levosimendan small molecule approved 141505-33-1 280.2847 C14H12N6O P63316#Troponin C, slow skeletal and cardiac muscles@Q14654#ATP-sensitive inward rectifier potassium channel 11@Q15842#ATP-sensitive inward rectifier potassium channel 8@Q14432#cGMP-inhibited 3',5'-cyclic phosphodiesterase A Levosimendan is a new Ca2+-sensitizing inotropic agent. Ca2+ sensitizers represent a new class of inotropic agents, which overcome the disadvantages associated with currently available inotropic agents in as they are not associated with an increased risk of arrhythmias, cell injury and death due to Ca2+ overload in myocardial cells; they do not increase the activation energy; and they have the potential to reverse contractile dysfunction under pathophysiologic conditions, such as acidosis or myocardial stunning. Levosimendan has not been approved for use in the U.S. or Canada. D0C4HG DB00923 Ceforanide small molecule approved 60925-61-3 519.554 C20H21N7O6S2 D6R448#Penicillin-binding protein 2 Ceforanide is a semisynthetic second-generation cephalosporin. The cephalosporins are bactericidal drugs with both gram-positive and gram-negative activity. They inhibit bacterial cell wall synthesis in a way similar to the penicillins. D06OUL DB00924 Cyclobenzaprine small molecule approved 303-53-7 275.3874 C20H21N P28223#5-hydroxytryptamine receptor 2A@P41595#5-hydroxytryptamine receptor 2B@P28335#5-hydroxytryptamine receptor 2C@P50406#5-hydroxytryptamine receptor 6@P31645#Sodium-dependent serotonin transporter@P23975#Sodium-dependent noradrenaline transporter@P34969#5-hydroxytryptamine receptor 7@O00206#Toll-like receptor 4@Q06278#Aldehyde oxidase Cyclobenzaprine is a skeletal muscle relaxant that works on areas of the brainstem to reduce skeletal muscle spasm, though its exact pharmacodynamic behaviour is currently unclear.15,16,10 Despite its long half-life, it is relatively short-acting with a typical duration of action of 4-6 hours.10 Cyclobenzaprine has been reported to contribute to the development of serotonin syndrome when used in combination with other serotonergic medications.15,16,5 Symptoms of serotonin syndrome may include autonomic instability, changes to mental status, neuromuscular abnormalities, or gastrointestinal symptoms - treatment with cyclobenzaprine should be discontinued immediately if any of these reactions occur during therapy.15,16 D01KHH DB00925 Phenoxybenzamine small molecule approved 59-96-1 303.826 C18H22ClNO P35348#Alpha-1A adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18825#Alpha-2C adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P0DP23#Calmodulin@P07550#Beta-2 adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor Phenoxybenzamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phenoxybenzamine is a long-acting, adrenergic, alpha-receptor blocking agent which can produce and maintain "chemical sympathectomy" by oral administration. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. Phenoxybenzamine works by blocking alpha receptors in certain parts of the body. Alpha receptors are present in the muscle that lines the walls of blood vessels. When the receptors are blocked by Phenoxybenzamine, the muscle relaxes and the blood vessels widen. This widening of the blood vessels results in a lowering of blood pressure. D0X2DK DB00927 Famotidine small molecule approved 76824-35-6 337.445 C8H15N7O2S3 P25021#Histamine H2 receptor Famotidine decreases the production of gastric acid, suppresses acid concentration and pepsin content, and decreases the volume of gastric secretion. Famotidine inhibits both basal and nocturnal gastric acid secretion, as well as acid secretion stimulated by food, caffeine, insulin, and pentagastrin.5,6 D0K0OZ DB00928 Azacitidine small molecule approved 320-67-2 244.2047 C8H12N4O5 P26358#DNA (cytosine-5)-methyltransferase 1 Azacitidine is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to azacitidine. Upon uptake into cells, azacitidine is phosphorylated to 5-azacytidine monophosphate by uridine-cytidine kinase, then to diphosphate by pyrimidine monophosphate kinases and triphosphate by diphosphate kinases. 5-Azacitidine triphosphate is incorporated into RNA, leading to the disruption of nuclear and cytoplasmic RNA metabolism and inhibition of protein synthesis. 5-Azacytidine diphosphate is reduced to 5-aza-deoxycytidine diphosphate by ribonucleotide reductase. The resultant metabolite is phosphorylated to 5-azadeoxycitidine triphosphate by nucleoside diphosphate kinases. 5-azadeoxycitidine triphosphate is then incoporated into DNA, leading to inhibition of DNA synthesis. Azacitidine is most toxic during the S-phase of the cell cycle. D09FAZ DB00929 Misoprostol small molecule approved 59122-46-2 382.5341 C22H38O5 P43115#Prostaglandin E2 receptor EP3 subtype@P43116#Prostaglandin E2 receptor EP2 subtype@P34995#Prostaglandin E2 receptor EP1 subtype@P35408#Prostaglandin E2 receptor EP4 subtype Misoprostol is a prostaglandin E1 analog used to reduce the risk of NSAID induced gastric ulcers by reducing secretion of gastric acid from parietal cells.3,13,14 Misoprostol is also used to manage miscarriages and used alone or in combination with mifepristone for first trimester abortions.4,2,6 An oral dose of misoprostol has an 8 minute onset of action and a duration of action of approximately 2 hours, a sublingual dose has an 11 minute onset of action and a duration of action of approximately 3 hours, a vaginal dose has a 20 minute onset of action and a duration of action of approximately 4 hours, and a rectal dose has a 100 minute onset of action and a duration of action of approximately 4 hours.7 D09ANG DB00931 Metacycline small molecule approved 914-00-1 442.424 C22H22N2O8 Methacycline is a tetracycline antibiotic. Similar to other tetracyclines, it has a wide spectrum of antimicrobial action. It is active against most Gram-positive bacteria (pneumococci, streptococci, staphylococci) and Gram-negative bacteria (E. coli, salmonella, shigella, etc.), and towards agents causing onithosis, psittacosis, trachoma, and some Protozoa. Like other tetracyclines, the general usefulness of methacycline has been reduced with the onset of bacterial resistance. DB00932 Tipranavir small molecule approved 174484-41-4 602.664 C31H33F3N2O5S Tipranavir is a non-peptidic protease inhibitor (PI) of HIV. Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. D0EV6T DB00933 Mesoridazine small molecule approved 5588-33-0 386.574 C21H26N2OS2 P28223#5-hydroxytryptamine receptor 2A Mesoridazine, the besylate salt of a metabolite of thioridazine, is a phenothiazine tranquilizer. Pharmacological studies in laboratory animals have established that mesoridazine has a spectrum of pharmacodynamic actions typical of a major tranquilizer. In common with other tranquilizers it inhibits spontaneous motor activity in mice, prolongs thiopental and hexobarbital sleeping time in mice and produces spindles and block of arousal reaction in the EEG of rabbits. It is effective in blocking spinal reflexes in the cut and antagonizes d-amphetamine excitation and toxicity in grouped mice. It shows a moderate adrenergic blocking activity in vitro and in vivo and antagonizes 5-hydroxytryptamine in vivo. Intravenously administered, it lowers the blood pressure of anesthetized dogs. It has a weak antiacetylcholine effect in vitro. D04AAN DB00934 Maprotiline small molecule approved 10262-69-8 277.4033 C20H23N P23975#Sodium-dependent noradrenaline transporter@P70174#Histamine H1 receptor@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5@P28223#5-hydroxytryptamine receptor 2A@P28335#5-hydroxytryptamine receptor 2C@P34969#5-hydroxytryptamine receptor 7 Maprotiline is a tetracyclic antidepressant. Although its main therapeutic use is in the treatment of depression, it has also been shown to exert a sedative effect on the anxiety component that often accompanies depression. In one sleep study, it was shown that maprotiline increases the duration of the REM sleep phase in depressed patients, compared to imipramine which reduced the REM sleep phase. Maprotiline is a strong inhibitor of noradrenaline reuptake in the brain and peripheral tissues, however it is worthy to note that it is a weak inhibitor of serotonergic uptake. In addition, it displays strong antihistaminic action (which may explain its sedative effects) as well as weak anticholinergic action. Maprotiline also has lower alpha adrenergic blocking activity than amitriptyline. D03KQF DB00935 Oxymetazoline small molecule approved 1491-59-4 260.3746 C16H24N2O P35348#Alpha-1A adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor@P18825#Alpha-2C adrenergic receptor@P35368#Alpha-1B adrenergic receptor@P25100#Alpha-1D adrenergic receptor@P08908#5-hydroxytryptamine receptor 1A@P28222#5-hydroxytryptamine receptor 1B@P28221#5-hydroxytryptamine receptor 1D Oxymetazoline is an adrenergic α1- and α2-agonist and a direct-acting sympathomimetic drug. By stimulating adrenergic receptors, oxymetazoline causes vasoconstriction of dilated arterioles and reduces blood flow.13 In a radioligand competition study, oxymetazoline displayed higher affinity at α1A-adrenoceptors compared to α2B-adrenoceptors, but with higher potency at α2B-adrenoceptors.5 When sprayed intranasally, oxymetazoline relieved relief nasal congestion and improved nasal airflow in patients with acute coryzal rhinitis for up to 12 hours following a single dose.10 D09EBS DB00936 Salicylic acid small molecule approved 69-72-7 138.1207 C7H6O3 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2@Q04828#Aldo-keto reductase family 1 member C1 Salicylic acid treats acne by causing skin cells to slough off more readily, preventing pores from clogging up. This effect on skin cells also makes salicylic acid an active ingredient in several shampoos meant to treat dandruff. Use of straight salicylic solution may cause hyperpigmentation on unpretreated skin for those with darker skin types (Fitzpatrick phototypes IV, V, VI), as well as with the lack of use of a broad spectrum sunblock. Subsalicylate in combination with bismuth form the popular stomach relief aid known commonly as Pepto-Bismol. When combined the two key ingredients help control diarrhea, nausea, heartburn, and even gas. It is also very mildly anti-biotic. DB00937 Diethylpropion small molecule approved 90-84-6 205.2961 C13H19NO P23975#Sodium-dependent noradrenaline transporter@Q01959#Sodium-dependent dopamine transporter Diethylpropion is a sympathomimetic stimulant drug marketed as an appetite suppressant. Chemically, it is the N,N-diethyl analog of cathinone. Its mechanism of action is similar to other appetite suppressants such as sibutramine, phentermine and dextroamphetamine. DB00938 Salmeterol small molecule approved 89365-50-4 415.5656 C25H37NO4 P07550#Beta-2 adrenergic receptor@P08588#Beta-1 adrenergic receptor@P13945#Beta-3 adrenergic receptor Salmeterol is a long acting beta-2 adrenergic receptor agonist that binds to both the active and exo sites of the beta-2 adrenergic receptor.1 Salmeterol has a longer duration of action than other beta-2 agonists like salbutamol.5 Patients should be counselled regarding the risks of long acting beta agonist (LABA) monotherapy, hypokalemia, hypoglycemia, and not to take this drug with another LABA.8,9,10,11,12 D0L5YV DB00939 Meclofenamic acid small molecule approved 644-62-2 296.149 C14H11Cl2NO2 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2@P09917#Arachidonate 5-lipoxygenase@O43526#Potassium voltage-gated channel subfamily KQT member 2@O43525#Potassium voltage-gated channel subfamily KQT member 3 Meclofenamic acid is a nonsteroidal agent which has demonstrated anti-inflammatory, analgesic, and antipyretic activity in laboratory animals. D08IFL DB00940 Methantheline small molecule approved 5818-17-7 340.436 C21H26NO3 P25021#Histamine H2 receptor@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5@P11229#Muscarinic acetylcholine receptor M1 Methantheline is a synthetic quarternary ammonium antimuscarinic used to relieve cramps or spasms of the stomach, intestines, and bladder. It can be used together with antacids or other medicines, such as H2-receptor antagonists, in the treatment of peptic ulcer. Methantheline inhibits muscarinic actions at postganglionic parasympathetic neuroeffector sites. D0JY5S DB00941 Hexafluronium small molecule approved 4844-10-4 502.745 C36H42N2 P06276#Cholinesterase Hexafluronium bromide is a cholinesterase antagonist that can be used to prolong the relaxation effects of succinylcholine or suxamethonium chloride. Suxamethonium acts as a depolarizing muscle relaxant. It imitates the action of acetylcholine at the neuromuscular junction and is degraded by pseudocholinesterase, a plasma cholinesterase. The prolonged stimulation of the acetylcholine receptor results first in disorganized muscle contractions, then in profound relaxation. Cholinesterases catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation. There are two types of cholinesterase acetylcholinesterase and pseuodocholinesterase. The first hydrolyses acetylcholine more quickly; the latter hydrolyses butyrylcholine and succinylcholine more quickly. An absence or mutation of the pseudocholinesterase enzyme leads to a medical condition known simply as pseudocholinesterase deficiency. This is a silent condition that only manifests itself when people who have the deficiency receive the muscle relaxants succinylcholine or mivacurium during a surgery. DB00942 Cycrimine small molecule approved 77-39-4 287.4397 C19H29NO P11229#Muscarinic acetylcholine receptor M1 Cycrimine is a central anticholenergic used in the treatment of the symptoms of Parkinson's disease. It is a drug used to reduce levels of acetylcholine. Acetylcholine is usually in balance with dopamine neurotransmitters, however lower levels of dopamine are present in the brain of patients suffering from Parkinson's disease. By lowering levels of acetylcholine, it is thought that this balance may be restored. D02LRQ DB00943 Zalcitabine small molecule approved 7481-89-2 211.2178 C9H13N3O3 Q72547#Reverse transcriptase/RNaseH Zalcitabine is an analog of 2'-deoxycytidine that is pharmacologically related to but structurally different from other nucleotide reverse transcriptase inhibitors (NRTIs). Zalcitabine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. D0Z9QR DB00944 Demecarium small molecule approved 16505-84-3 556.7797 C32H52N4O4 P22303#Acetylcholinesterase@P06276#Cholinesterase Demecarium is a long-acting cholinesterase inhibitor and potent miotic. Because of its toxicity, it should be reserved for use in patients with open-angle glaucoma or other chronic glaucomas not satisfactorily controlled with the short-acting miotics and other agents. Application of demecarium to the eye produces intense miosis and ciliary muscle contraction due to inhibition of cholinesterase, allowing acetylcholine to accumulate at sites of cholinergic transmission. These effects are accompanied by increased capillary permeability of the ciliary body and iris, increased permeability of the blood-aqueous barrier, and vasodilation. Myopia may be induced or, if present, may be augmented by the increased refractive power of the lens that results from the accommodative effect of the drug. DB00945 Acetylsalicylic acid small molecule approved 50-78-2 180.1574 C9H8O4 P35354#Prostaglandin G/H synthase 2 Effects on pain and fever DB00946 Phenprocoumon small molecule approved 435-97-2 280.3178 C18H16O3 Q9BQB6#Vitamin K epoxide reductase complex subunit 1 Phenprocoumon, a coumarin anticoagulant, thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as phenprocoumon have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body). However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae. D0QV5T DB00947 Fulvestrant small molecule approved 129453-61-8 606.78 C32H47F5O3S P03372#Estrogen receptor Fulvestrant for intramuscular administration is an estrogen receptor antagonist without known agonist effects. D0JO7Y DB00948 Mezlocillin small molecule approved 51481-65-3 539.582 C21H25N5O8S2 A0A0E1R3H3#Penicillin-binding protein 3 Mezlocillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Mezlocillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of mezlocillin results from the inhibition of cell wall synthesis and is mediated through mezlocillin binding to penicillin binding proteins (PBPs). Mezlocillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Mezlocillin can be used to treat susceptible strains of H. influenzae, Klebsiella species, Pseudomonas species, Proteus mirabilis, E. coli, Enterobacter species, Streptococcus faecelis, Peptococcus species, Peptostreptococcus species, Bacteriodes species (including B. fragilis), Morganella morganii, Serratia species, N. gonorrhoeae, P. vulgaris, and Providencia rettgeri. This drug is discontinued in the U.S. D00NJJ DB00949 Felbamate small molecule approved 25451-15-4 238.2399 C11H14N2O4 Q13224#Glutamate receptor ionotropic, NMDA 2B@Q12879#Glutamate receptor ionotropic, NMDA 2A Felbamate is an antiepileptic indicated as monotherapy or as an adjunct to other anticonvulsants for the treatment of partial seizures resulting from epilepsy. Receptor-binding studies in vitro indicate that felbamate has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding, and is devoid of activity at the MK-801 receptor binding site of the NMDA receptor-ionophore complex. However, felbamate does interact as an antagonist at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex. D05KON DB00950 Fexofenadine small molecule approved 83799-24-0 501.6564 C32H39NO4 P70174#Histamine H1 receptor Fexofenadine relieves allergy symptoms by antagonizing the actions of histamine, an endogenous compound predominantly responsible for allergic symptomatology.10 The relatively long duration of action of fexofenadine (approximately 24 hours)7 allows for once or twice daily dosing, and its rapid absorption allows for an onset of action within 1-3 hours. Fexofenadine should not be taken with fruit juice, as this may impair its absorption.10 D01KPV DB00951 Isoniazid small molecule approved 54-85-3 137.1393 C6H7N3O P9WIE5#Catalase-peroxidase@A0A6L8PBX8#Enoyl-[acyl-carrier-protein] reductase [NADH]@P10632#Cytochrome P450 2C8@P05177#Cytochrome P450 1A2@P08684#Cytochrome P450 3A4@P33261#Cytochrome P450 2C19@P00378#Dihydrofolate reductase Isoniazid is a bactericidal agent active against organisms of the genus Mycobacterium, specifically M. tuberculosis, M. bovis and M. kansasii. It is a highly specific agent, ineffective against other microorganisms. Isoniazid is bactericidal when mycobacteria grow rapidly and bacteriostatic when they grow slowly. D09XQF DB00952 Naratriptan small molecule approved 121679-13-8 335.464 C17H25N3O2S P08908#5-hydroxytryptamine receptor 1A@P28221#5-hydroxytryptamine receptor 1D@P28222#5-hydroxytryptamine receptor 1B@P30939#5-hydroxytryptamine receptor 1F Naratriptan is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. It is structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonist. Naratriptan has only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Naratriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Naratriptan in humans. D0T3KI DB00953 Rizatriptan small molecule approved 144034-80-0 269.3449 C15H19N5 P28221#5-hydroxytryptamine receptor 1D@P28222#5-hydroxytryptamine receptor 1B@P30939#5-hydroxytryptamine receptor 1F Rizatriptan is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. It is structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonists and has only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Rizatriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Rizatriptan in humans. D0S9MU DB00955 Netilmicin small molecule approved 56391-56-1 475.587 C21H41N5O7 P0A7S3#30S ribosomal protein S12 Netilmicin is a semisynthetic, water soluble antibiotic of the aminoglycoside group, produced by the fermentation of Micromonospora inyoensis, a species of actinomycete. Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. It is active at low concentrations against a wide variety of pathogenic bacteria including Escherichia coli, bacteria of the Klebsiella-Enterobacter-Serratia group, Citrobacter sp., Proteus sp. (indole-positive and indole-negative), including Proteus mirabilis, P. morganii, P. rettgrei, P. vulgaris, Pseudomonas aeruginosa and Neisseria gonorrhoea. Netilmicin is also active in vitro against isolates of Hemophilus influenzae, Salmonella sp., Shigella sp. and against penicillinase and non-penicillinase-producing Staphylococcus including methicillin-resistant strains. Some strains of Providencia sp., Acinetobacter sp. and Aeromonas sp. are also sensitive to netilmicin. Many strains of the above organisms which are found to be resistant to other aminoglycosides, such as kanamycin, gentamicin, tobramycin and sisomicin, are susceptible to netilmicin in vitro. Occasionally, strains have been identified which are resistant to amikacin but susceptible to netilmicin. The combination of netilmicin and penicillin G has a synergistic bactericidal effect against most strains of Streptococcus faecalis (enterococcus). The combined effect of netilmicin and carbenicillin or ticarcillin is synergistic for many strains of Pseudomonas aeruginosa. In addition, many isolates of Serratia, which are resistant to multiple antibiotics, are inhibited by synergistic combinations of netilmicin with carbenicillin, azlocillin, mezlocillin, cefamandole, cefotaxime or moxalactam. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses. D07JZF DB00956 Hydrocodone small molecule approved 125-29-1 299.3642 C18H21NO3 P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@Q99720#Sigma non-opioid intracellular receptor 1 Hydrocodone inhibits pain signaling in both the spinal cord and brain 12. Its actions in the brain also produce euphoria, respiratory depression, and sedation. D0X5KF DB00957 Norgestimate small molecule approved 35189-28-7 369.4971 C23H31NO3 P03372#Estrogen receptor@P10275#Androgen receptor@P06401#Progesterone receptor Norgestimate is a progestin that suppresses ovulation for contraception and reduces free testosterone to treat moderate acne vulgaris.7,10,11 The therapeutic index is wide as overdoses are rare.10,11 Patients should be counselled regarding the risk of vascular problems, liver disease, hypertension, metabolic effects, headaches, and bleeding irregularities.10,11 D09QZI DB00958 Carboplatin small molecule approved 41575-94-4 371.254 C6H12N2O4Pt Carboplatin is an organoplatinum antineoplastic alkylating agent used in the treatment of advanced ovarian carcinoma.9 Carboplatin has a long duration of action as it is given every 4 weeks, and a narrow therapeutic index.9 Patients should be counselled regarding bone marrow suppression and anemia.9 D0X7HM DB00959 Methylprednisolone small molecule approved 83-43-2 374.4706 C22H30O5 P04150#Glucocorticoid receptor@P04083#Annexin A1 Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.5 Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.5 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.5 D08PIQ DB00960 Pindolol small molecule approved 13523-86-9 248.3208 C14H20N2O2 P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P28222#5-hydroxytryptamine receptor 1B@P13945#Beta-3 adrenergic receptor@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor Pindolol is a nonselective beta blocker indicated in the management of hypertension9 and prophylaxis of angina.10 It has a short duration of action as it is given twice daily, and a wide therapeutic window as doses can range from 10-60 mg/day.9 Patients should be counselled regarding the risk of cardiac failure, exacerbating ischemic heart disease with sudden withdrawal, nonallergic bronchospasm, masking hypoglycemia in diabetics, and masking hyperthyroidism.9 D0F2PO DB00961 Mepivacaine small molecule approved 96-88-8 246.348 C15H22N2O Q9Y5Y9#Sodium channel protein type 10 subunit alpha Mepivicaine is an amide local anesthetic. Mepivicaine as a reasonably rapid onset and medium duration and is known by the proprietary names as Carbocaine and Polocaine. Mepivicaine is used in local infiltration and regional anesthesia. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with normal therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. D0WO8W DB00962 Zaleplon small molecule approved 151319-34-5 305.3339 C17H15N5O P14867#Gamma-aminobutyric acid receptor subunit alpha-1 Zaleplon is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zaleplon is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex. Subunit modulation of the GABABZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zaleplon also binds selectively to the CNS GABAA-receptor chloride ionophore complex at benzodiazepine(BZ) omega-1 (BZ1, ο1) receptors. D09DWL DB00963 Bromfenac small molecule approved 91714-94-2 334.165 C15H12BrNO3 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1 Bromfenac ophthalmic solution is a sterile, topical, nonsteroidal anti-inflammatory drug (NSAID) for ophthalmic use. D0U1OM DB00964 Apraclonidine small molecule approved 66711-21-5 245.109 C9H10Cl2N4 P35348#Alpha-1A adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor Apraclonidine significantly lowers intraocular pressure with minimal effects on cardiovascular and pulmonary parameters. It lowers intraocular pressure by reducing aqueous humor production and increasing uveoscleral outflow. D0MT0M DB00966 Telmisartan small molecule approved 144701-48-4 514.6169 C33H30N4O2 P37231#Peroxisome proliferator-activated receptor gamma@P30556#Type-1 angiotensin II receptor Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT1 receptor subtype. It has the highest affinity for the AT1 receptor among commercially available ARBS and has minimal affinity for the AT2 receptor. New studies suggest that telmisartan may also have PPARγ agonistic properties that could potentially confer beneficial metabolic effects, as PPARγ is a nuclear receptor that regulates specific gene transcription, and whose target genes are involved in the regulation of glucose and lipid metabolism, as well as anti-inflammatory responses. This observation is currently being explored in clinical trials. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan works by blocking the vasoconstrictor and aldosterone secretory effects of angiotensin II. D0N6RF DB00967 Desloratadine small molecule approved 100643-71-8 310.821 C19H19ClN2 P70174#Histamine H1 receptor Desloratadine is a long-acting second-generation H1-receptor antagonist which has a selective and peripheral H1-antagonist action. Histamine is a chemical that causes many of the signs that are part of allergic reactions, such as the swelling of tissues. Histamine is released from histamine-storing cells (mast cells) and attaches to other cells that have receptors for histamine. The attachment of the histamine to the receptors causes the cell to be "activated," releasing other chemicals which produce the effects that we associate with allergies. Desloratadine blocks one type of receptor for histamine (the H1 receptor) and thus prevents activation of cells by histamine. Unlike most other antihistamines, Desloratadine does not enter the brain from the blood and, therefore, does not cause drowsiness. D01GBY DB00968 Methyldopa small molecule approved 555-30-6 211.2145 C10H13NO4 P20711#Aromatic-L-amino-acid decarboxylase@P08913#Alpha-2A adrenergic receptor Antihypertensive effects of methyldopa are mostly mediated by its pharmacologically active metabolite, alpha-methylnorepinephrine, which works as an agonist at central inhibitory alpha-adrenergic receptors.11 Stimulation of alpha-adrenergic receptors leads to decreased peripheral sympathetic tone and reduced arterial pressure.3 Methyldopa causes a net reduction in the tissue concentration of serotonin, dopamine, norepinephrine, and epinephrine. Overall, methyldopa lowers both standing blood pressure and especially supine blood pressure, with infrequent symptomatic postural hypotension. Methyldopa also reduces plasma renin activity but has negligible effects on glomerular filtration rate, renal blood flow, or filtration fraction. It also has no direct effect on cardiac function but in some patients, a slowed heart rate may occur.11 D0BA6T DB00969 Alosetron small molecule approved 122852-42-0 294.351 C17H18N4O P46098#5-hydroxytryptamine receptor 3A Alosetron is a potent and selective antagonist of the serotonin 5-HT3 receptor type. Activation of these receptors and the resulting neuronal depolarization affects the regulation of visceral pain, colonic transit, and GI secretions processes that are related to IBS. By blocking these receptors, alosetron is able to effectively control IBS. D06GKN DB00970 Dactinomycin small molecule approved 50-76-0 1255.417 C62H86N12O16 P11388#DNA topoisomerase 2-alpha@Q02880#DNA topoisomerase 2-beta Generally, the actinomycins exert an inhibitory effect on gram-positive and gram-negative bacteria and on some fungi. However, the toxic properties of the actinomycins (including dactinomycin) in relation to antibacterial activity are such as to preclude their use as antibiotics in the treatment of infectious diseases. Because the actinomycins are cytotoxic, they have an antineoplastic effect which has been demonstrated in experimental animals with various types of tumor implant. This cytotoxic action is the basis for their use in the treatment of certain types of cancer. Dactinomycin is believed to produce its cytotoxic effects by binding DNA and inhibiting RNA synthesis. D0P8IV DB00971 Selenium Sulfide small molecule approved 7488-56-4 143.09 S2Se Selenium sulfide is an antifungal agent often used in shampoos for the treatment of dandruff and seborrheic dermatitis. Selenium sulfide is highly active in inhibiting the growth of P. ovale. It is also a proven cytostatic agent, slowing the growth of both hyperproliferative and normal cells in dandruff and seborrheic dermatitis. A 0.6% micronized form of selenium sulfide is also safe and effective for dandruff. DB00972 Azelastine small molecule approved 58581-89-8 381.898 C22H24ClN3O P35367#Histamine H1 receptor@Q16873#Leukotriene C4 synthase@P04054#Phospholipase A2 D00JVR DB00973 Ezetimibe small molecule approved 163222-33-1 409.4252 C24H21F2NO3 Q9UHC9#Niemann-Pick C1-like protein 1@P35610#Sterol O-acyltransferase 1@P15144#Aminopeptidase N Ezetimibe was shown to reduce the levels of total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG), and increase high-density lipoprotein cholesterol (HDL-C) in patients with hyperlipidemia.5 This therapeutic effect was more profound when ezetimibe was co-administered with a statin or fenofibrate compared to either treatment alone.5 In clinical trials involving patients with homozygous and heterozygous familial hypercholesterolemia and in those with sitosterolemia, a recommended therapeutic dose of ezetimibe was effective in reducing the LDL levels by 15-20% while increasing HDL-C by 2.5-5%.4 D09LWS DB00974 Edetic acid small molecule approved 60-00-4 292.2426 C10H16N2O8 Edetate calcium is a heavy metal chelating agent. The calcium in edetate calcium can be displaced by divalent or trivalent metals to form a stable water soluble complex that can be excreted in the urine. In theory, 1 g of edetate calcium can theoretically bind 620 mg of lead, but in reality only about 5 mg per gram is actually excreted into the urine in lead poisoned patients. In addition to chelating lead, edetate calcium also chelates and eliminates zinc from the body. Edetate calcium also binds cadmium, copper, iron and manganese, but to a much lesser extent than either lead or zinc. Edetate calcium is relatively ineffective for use in treating mercury, gold or arsenic poisoning. D00KEP DB00975 Dipyridamole small molecule approved 58-32-2 504.6256 C24H40N8O4 Q9Y233#cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A@O76074#cGMP-specific 3',5'-cyclic phosphodiesterase@P27815#cAMP-specific 3',5'-cyclic phosphodiesterase 4A@Q8IJA9#Adenosine deaminase@P53805#Calcipressin-1@P02763#Alpha-1-acid glycoprotein 1 Dipyridamole, a non-nitrate coronary vasodilator that also inhibits platelet aggregation, is combined with other anticoagulant drugs, such as warfarin, to prevent thrombosis in patients with valvular or vascular disorders. Dipyridamole is also used in myocardial perfusion imaging, as an antiplatelet agent, and in combination with aspirin for stroke prophylaxis. D0F9GE DB00976 Telithromycin small molecule approved 191114-48-4 812.018 C43H65N5O10 Telithromycin is a ketolide antibiotic which has an antimicrobial spectrum similar or slightly broader than that of penicillin. It is often used as an alternative in patients who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma. Telithromycin prevents bacterial growth by binding to bacterial 50S ribosomal subunits and interfering with bacterial peptide translocation and elongation. D09HNR DB00977 Ethinylestradiol small molecule approved 57-63-6 296.4034 C20H24O2 P03372#Estrogen receptor@O75469#Nuclear receptor subfamily 1 group I member 2 Ethinylestradiol is a synthetic estrogen that decreases luteinizing hormone to decrease endometrial vascularization, and decreases gonadotrophic hormone to prevent ovulation.13,12,15 It has a long duration of action as it is taken once daily, and a wide therapeutic index as overdoses are generally not associated with serious adverse effects.15 Patients should be counselled regarding the risks of thrombotic events.15 DB00978 Lomefloxacin small molecule approved 98079-51-7 351.3479 C17H19F2N3O3 P11388#DNA topoisomerase 2-alpha Lomefloxacin is a fluoroquinolone antibiotic used to treat chronic bronchitis, as well as complicated and uncomplicated urinary tract infections. It is also used as a prophylactic or preventative treatment to prevent urinary tract infections in patients undergoing transrectal or transurethral surgical procedures. Flouroquinolones such as lomefloxacin possess excellent activity against gram-negative aerobic bacteria such as E.coli and Neisseria gonorrhoea as well as gram-positive bacteria including S. pneumoniae and Staphylococcus aureus. They also posses effective activity against shigella, salmonella, campylobacter, gonococcal organisms, and multi drug resistant pseudomonas and enterobacter. D02KOF DB00979 Cyclopentolate small molecule approved 512-15-2 291.3853 C17H25NO3 P11229#Muscarinic acetylcholine receptor M1 Cyclopentolate is an anti-muscarinic in the same class as atropine and scopolamine. Cyclopentolate blocks the receptors in the muscles of the eye (muscarinic receptors). These receptors are involved controlling the pupil size and the shape of the lens. Cyclopentolate thus induces relaxation of the sphincter of the iris and the ciliary muscles. When applied topically to the eyes, it causes a rapid, intense cycloplegic and mydriatic effect that is maximal in 15 to 60 minutes; recovery usually occurs within 24 hours. The cycloplegic and mydriatic effects are slower in onset and longer in duration in patients who have dark pigmented irises. D0B1EV DB00980 Ramelteon small molecule approved 196597-26-9 259.3434 C16H21NO2 P49286#Melatonin receptor type 1B@P48039#Melatonin receptor type 1A Ramelteon is the first selective melatonin agonist. It works by mimicking melatonin (MT), a naturally occuring hormone that is produced during the sleep period and thought to be responsible for the regulation of circadian rhythm underlying the normal sleep-wake cycle. Ramelteon has a high affinity for the MT1 and MT2 receptors. The MT1 and MT2 receptors are located in the brain's suprachiasmatic nuclei (SCN),which is known as the body's "master clock" because it regulates the 24-hour sleep-wake cycle. Ramelteon has an active metabolite that is less potent but circulates in higher concentrations than the parent compound. The metabolite also has weak affinity for the 5HT2b receptor. D0U0KW DB00981 Physostigmine small molecule approved 57-47-6 275.3461 C15H21N3O2 P22303#Acetylcholinesterase@P43681#Neuronal acetylcholine receptor subunit alpha-4@P17787#Neuronal acetylcholine receptor subunit beta-2 Physostigmine is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor which effectively increases the concentration of acetylcholine at the sites of cholinergic transmission. Physostigmine is used to treat glaucoma. Because it crosses the blood-brain barrier, it is also used to treat the central nervous system effects of atropine overdose and other anticholinergic drug overdoses. Physostigmine can reverse both central and peripheral anticholinergia. D09JVV DB00982 Isotretinoin small molecule approved 4759-48-2 300.4351 C20H28O2 P13631#Retinoic acid receptor gamma@P10276#Retinoic acid receptor alpha The pharmacodynamics of isotretinoin are poorly understood.Label D00DKK DB00983 Formoterol small molecule approved 73573-87-2 344.4049 C19H24N2O4 P07550#Beta-2 adrenergic receptor@P08588#Beta-1 adrenergic receptor@P13945#Beta-3 adrenergic receptor Formoterol works locally in the lungs as a bronchodilator, relaxing smooth muscle and opening up the airways. It possesses both a rapid onset of action (approximately 2-3 minutes)8 and a long duration of action (up to 12 hours).16 The use of long-acting beta-agonists (LABAs), such as formoterol, without concomitant inhaled corticosteroids in asthmatic patients should be avoided, as LABA monotherapy has been associated with an increased risk of asthma-related death.16 D04KJO DB00984 Nandrolone phenpropionate small molecule approved 62-90-8 406.5571 C27H34O3 P10275#Androgen receptor Nandrolone is an anabolic steroid occurring naturally in the human body, albeit in small quantities. Nandrolone increases production and urinary excretion of erythropoietin. It may also have a direct action on bone marrow. Nandrolone binds to the androgen receptor to a greater degree than testosterone, but due to its inability to act on the muscle in ways unmediated by the receptor, has less overall effect on muscle growth. DB00985 Dimenhydrinate small molecule approved 523-87-5 469.97 C24H28ClN5O3 P70174#Histamine H1 receptor Dimenhydrinate is indicated for the prevention and treatment of nausea, vomiting, or vertigo of motion sickness.9,10 It has a short duration of action of 4-8 hours.4 Patients should be counselled regarding pronounced drowsiness, avoiding alcohol and other sedatives, and exercising caution when operating a motor vehicle or heavy machinery.9 D0U8UV DB00986 Glycopyrronium small molecule approved 740028-90-4 318.4305 C19H28NO3 P11229#Muscarinic acetylcholine receptor M1@P20309#Muscarinic acetylcholine receptor M3@P08172#Muscarinic acetylcholine receptor M2@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5 Glycopyrronium is a quaternary ammonium compound that is one of the most commonly prescribed long acting muscarinic antagonists.2,3,15 Glycopyrronium slowly dissociated from muscarinic receptors, leading to a long duration of action.1 It has a wider therapeutic index than other anticholinergic medications, such as tiotropium.8 Patients should be counselled regarding the risk of worsening urinary retention, risk of overheating, and transient blurred vision.12 DB00987 Cytarabine small molecule approved 147-94-4 243.2166 C9H13N3O5 P06746#DNA polymerase beta Cytarabine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute myelogenous leukemia and meningeal leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Cytarabine is metabolized intracellularly into its active triphosphate form (cytosine arabinoside triphosphate). This metabolite then damages DNA by multiple mechanisms, including the inhibition of alpha-DNA polymerase, inhibition of DNA repair through an effect on beta-DNA polymerase, and incorporation into DNA. The latter mechanism is probably the most important. Cytotoxicity is highly specific for the S phase of the cell cycle. D07XSN DB00988 Dopamine small molecule approved 51-61-6 153.1784 C8H11NO2 Q01959#Sodium-dependent dopamine transporter@P09172#Dopamine beta-hydroxylase@P08908#5-hydroxytryptamine receptor 1A@P34969#5-hydroxytryptamine receptor 7@P23975#Sodium-dependent noradrenaline transporter@P31645#Sodium-dependent serotonin transporter@P46098#5-hydroxytryptamine receptor 3A@O95264#5-hydroxytryptamine receptor 3B@P00441#Superoxide dismutase [Cu-Zn]@Q05940#Synaptic vesicular amine transporter Dopamine is a natural catecholamine formed by the decarboxylation of 3,4-dihydroxyphenylalanine (DOPA). It is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system, especially in the nigrostriatal tract, and in a few peripheral sympathetic nerves. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings. D0T7OW DB00989 Rivastigmine small molecule approved 123441-03-2 250.3367 C14H22N2O2 P22303#Acetylcholinesterase@P06276#Cholinesterase Rivastigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. Tacrine is postulated to exert its therapeutic effect by enhancing cholinergic function. While the precise mechanism of rivastigmine's action is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by cholinesterase. If this proposed mechanism is correct, rivastigmine's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact. D0WY5Q DB00990 Exemestane small molecule approved 107868-30-4 296.4034 C20H24O2 P11511#Aromatase D0D2VS DB00991 Oxaprozin small molecule approved 21256-18-8 293.3166 C18H15NO3 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Oxaprozin is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Oxaprozin is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and to alleviate moderate pain. D0M9DC DB00992 Methyl aminolevulinate small molecule approved 33320-16-0 145.1564 C6H11NO3 After topical application of methyl aminolevulinate, porphyrins will accumulate intracellularly in the treated skin lesions. The intracellular porphyrins (including PpIX) are photoactive, fluorescing compounds and, upon light activation in the presence of oxygen, singlet oxygen is formed which causes damage to cellular compartments, in particular the mitochondria. Light activation of accumulated porphyrins leads to a photochemical reaction and thereby phototoxicity to the light-exposed target cells. D0OL6O DB00993 Azathioprine small molecule approved 446-86-6 277.263 C9H7N7O2S P63000#Ras-related C3 botulinum toxin substrate 1 Azathioprine is an immunosuppressive agent which functions through modulation of rac1 to induce T cell apoptosis, as well as other unknown immunosuppressive functions.5 It has a long duration of action as it is given daily, and has a narrow therapeutic index.12 Patients should be counselled regarding the risk of malignancies of the skin and lymphomas.12 D07QCE DB00995 Auranofin small molecule approved 34031-32-8 678.484 C20H34AuO9PS P30044#Peroxiredoxin-5, mitochondrial@O14920#Inhibitor of nuclear factor kappa-B kinase subunit beta Auranofin is a gold salt used in treating inflammatory arthritis. Gold salts are called second-line drugs because they are often considered when the arthritis progresses in spite of antiinflammatory drugs (NSAIDs and corticosteroids). D0L2UN DB00996 Gabapentin small molecule approved 60142-96-3 171.2368 C9H17NO2 P54289#Voltage-dependent calcium channel subunit alpha-2/delta-1@Q9NY47#Voltage-dependent calcium channel subunit alpha-2/delta-2@P30542#Adenosine receptor A1@O43525#Potassium voltage-gated channel subfamily KQT member 3@Q9NR82#Potassium voltage-gated channel subfamily KQT member 5 Gabapentin is an anti-convulsant medication that inhibits the release of excitatory neurotransmitters, allowing for its use against pathologic neurotransmission such as that seen in neuropathic pain and seizure disorders.16,19 It has a wide therapeutic index, with doses in excess of 8000 mg/kg failing to cause a fatal reaction in rats.21 D0J0ZS DB00997 Doxorubicin small molecule approved 23214-92-8 543.5193 C27H29NO11 P11388#DNA topoisomerase 2-alpha@Q14978#Nucleolar and coiled-body phosphoprotein 1@Q06AK7#DNA topoisomerase 1@Q02880#DNA topoisomerase 2-beta Doxorubicin is an antineoplastic in the anthracycline class. General properties of drugs in this class include: interaction with DNA in a variety of different ways including intercalation (squeezing between the base pairs), DNA strand breakage and inhibition with the enzyme topoisomerase II. Most of these compounds have been isolated from natural sources and antibiotics. However, they lack the specificity of the antimicrobial antibiotics and thus produce significant toxicity. The anthracyclines are among the most important antitumor drugs available. Doxorubicin is widely used for the treatment of several solid tumors while daunorubicin and idarubicin are used exclusively for the treatment of leukemia. Doxorubicin may also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA. Doxorubicin possesses an antitumor effect against a wide spectrum of tumors, either grafted or spontaneous. The anthracyclines are cell cycle-nonspecific. D07VLY DB00998 Frovatriptan small molecule approved 158747-02-5 243.3043 C14H17N3O P28221#5-hydroxytryptamine receptor 1D@P28222#5-hydroxytryptamine receptor 1B Frovatriptan is a second generation triptan 5-HT receptor agonist that binds with high affinity for 5-HT1B and 5-HT1D receptors. It is structurally distinct from, but pharmacologically related to other selective 5-HT1B/1D receptor agonists. Frovatriptan has no significant effects on GABAA mediated channel activity and has no significant affinity for benzodiazepine binding sites. Frovatriptan is believed to act on extracerebral, intracranial arteries and to inhibit excessive dilation of these vessels in migraine. Research has shown that migraine can be caused by the swelling of blood vessels around the brain. Frovatriptan eases the pain associated with migraine by narrowing these blood vessels. Frovatriptan has one of the highest affinities for the 5-HT1B of the second-generation triptan agonists. D06FPQ DB00999 Hydrochlorothiazide small molecule approved 58-93-5 297.739 C7H8ClN3O4S2 P55017#Solute carrier family 12 member 3@Q12791#Calcium-activated potassium channel subunit alpha-1 Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine.2,3,4,10,11 Hydrochlorothiazide has a wide therapeutic window as dosing is individualized and can range from 25-100mg.10,11 Hydrochlorothiazide should be used with caution in patients with reduced kidney or liver function.10,11 D0U4UQ DB01000 Cyclacillin small molecule approved 3485-14-1 341.426 C15H23N3O4S Q8DR59#Penicillin-binding protein 1A@P0AEB2#D-alanyl-D-alanine carboxypeptidase DacA@P24228#D-alanyl-D-alanine carboxypeptidase DacB@P08506#D-alanyl-D-alanine carboxypeptidase DacC@P02919#Penicillin-binding protein 1B Cyclacillin, a penicillin, is a cyclohexylamido analog of penicillanic acid. Cyclacillin is more resistant to beta-lactamase hydrolysis than ampicillin, is much better absorbed when given by mouth and, as a result, the levels reached in the blood and in the urine are considerably higher than those obtained with the same dose of ampicillin. Cyclacillin has been replaced by newer penicillin treatments. D00HWO DB01001 Salbutamol small molecule approved 18559-94-9 239.3107 C13H21NO3 P07550#Beta-2 adrenergic receptor@P08588#Beta-1 adrenergic receptor@P13945#Beta-3 adrenergic receptor Salbutamol (INN) or albuterol (USAN), a moderately selective beta(2)-receptor agonist similar in structure to terbutaline, is widely used as a bronchodilator to manage asthma and other chronic obstructive airway diseases.Label,3,4 The R-isomer, levalbuterol, is responsible for bronchodilation while the S-isomer increases bronchial reactivity.2 The R-enantiomer is available and sold in its pure form as levalbuterol and subsequently may produce fewer side-effects with only the R-enantiomer present - although this has not been formally demonstrated.2 D0K5CB DB01002 Levobupivacaine small molecule approved 27262-47-1 288.4277 C18H28N2O Q9Y5Y9#Sodium channel protein type 10 subunit alpha Levobupivacaine, a local anesthetic agent, is indicated for the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures. D09QUQ DB01003 Cromoglicic acid small molecule approved 16110-51-3 468.3665 C23H16O11 P25815#Protein S100-P Cromoglicate or cromolyn (USAN), a synthetic compound, inhibits antigen-induced bronchospasms and, hence, is used to treat asthma and allergic rhinitis. Cromoglicate is used as an ophthalmic solution to treat conjunctivitis and is taken orally to treat systemic mastocytosis and ulcerative colitis. DB01004 Ganciclovir small molecule approved 82410-32-0 255.2306 C9H13N5O4 P09252#DNA polymerase catalytic subunit@P13159#Thymidine kinase Ganciclovir is a synthetic nucleoside analogue of 2'-deoxyguanosine that inhibits replication of herpes viruses both in vitro and in vivo. Sensitive human viruses include cytomegalovirus (CMV), herpes simplex virus -1 and -2 (HSV-1, HSV-2), Epstein-Barr virus (EBV) and varicella zoster virus (VZV), however clinical studies have been limited to assessment of efficacy in patients with CMV infection. Ganciclovir is a prodrug that is structurally similar to acyclovir. It inhibits virus replication by its encorporation into viral DNA. This encorporation inhibits dATP and leads to defective DNA, ceasing or retarding the viral machinery required to spread the virus to other cells. D05ARP DB01005 Hydroxyurea small molecule approved 127-07-1 76.0547 CH4N2O2 P23921#Ribonucleoside-diphosphate reductase large subunit Hydroxyurea has dose-dependent synergistic activity with cisplatin in vitro. In vivo Hydroxyurea showed activity in combination with cisplatin against the LX-1 and CALU-6 human lung xenografts, but minimal activity was seen with the NCI-H460 or NCI-H520 xenografts. Hydroxyurea was synergistic with cisplatin in the Lewis lung murine xenograft. Sequential exposure to Hydroxyurea 4 hours before cisplatin produced the greatest interaction. D07CWD DB01006 Letrozole small molecule approved 112809-51-5 285.3027 C17H11N5 P11511#Aromatase Letrozole is an aromatase inhibitor used in the treatment of breast cancer. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing recurrence of the breast tumor tissue. D0C1WH DB01007 Tioconazole small molecule approved 65899-73-2 387.711 C16H13Cl3N2OS Q16850#Lanosterol 14-alpha demethylase Tioconazole is a broad-spectrum imidazole antifungal agent that inhibits the growth of human pathogenic yeasts. Tioconazole exhibits fungicidal activity in vitro against Candida albicans, other species of the genus Candida, and against Torulopsis glabrata. Tioconazole prevents the growth and function of some fungal organisms by interfering with the production of substances needed to preserve the cell membrane. This drug is effective only for infections caused by fungal organisms. It will not work for bacterial or viral infections. D0CA6J DB01008 Busulfan small molecule approved 55-98-1 246.302 C6H14O6S2 Busulfan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn leads to a miscoding of DNA. Alkylating agents are cell cycle-nonspecific and work by three different mechanisms, all of which achieve the same end result - disruption of DNA function and cell death. Overexpression of MGST2, a glutathione s-transferase, is thought to confer resistance to busulfan. The role of MGST2 in the metabolism of busulfan is unknown however. D07SUG DB01009 Ketoprofen small molecule approved 22071-15-4 254.2806 C16H14O3 P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1@P25024#C-X-C chemokine receptor type 1 Ketoprofen is a nonsteroidal anti-inflammatory agent (NSAIA) with analgesic and antipyretic properties. Ketoprofen has pharmacologic actions similar to those of other prototypical NSAIDs, which inhibit prostaglandin synthesis. Ketoprofen is used to treat rheumatoid arthritis, osteoarthritis, dysmenorrhea, and alleviate moderate pain. D0W9WF DB01010 Edrophonium small molecule approved 312-48-1 166.2401 C10H16NO P06276#Cholinesterase@P22303#Acetylcholinesterase Edrophonium is a short and rapid-acting anticholinesterase drug. Its effect is manifest within 30 to 60 seconds after injection and lasts an average of 10 minutes. Edrophonium's pharmacologic action is due primarily to the inhibition or inactivation of acetylcholinesterase at sites of cholinergic transmission. Nicotinic acetylcholine (nAChR)receptors are found throughout the body, especially on muscle. Stimulation of these receptors causes to muscle contraction. In myasthenia gravis the body's immune system destroys many of the nicotinic acetylcholine receptors, so that the muscle becomes less responsive to nervous stimulation. Edrophonium chloride increases the amount of acetylcholine at the nerve endings. Increased levels of acetylcholine allow the remaining receptors to function more efficiently. D0S5LH DB01011 Metyrapone small molecule approved 54-36-4 226.2738 C14H14N2O P15538#Cytochrome P450 11B1, mitochondrial@P00183#Camphor 5-monooxygenase Metopirone is an inhibitor of endogenous adrenal corticosteroid synthesis. D0Q9JT DB01012 Cinacalcet small molecule approved 226256-56-0 357.412 C22H22F3N D03YGR DB01013 Clobetasol propionate small molecule approved 25122-46-7 466.97 C25H32ClFO5 P04150#Glucocorticoid receptor@P04083#Annexin A1@P08235#Mineralocorticoid receptor Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.5 Clobetasol propionate is generally applied twice daily so the duration of action is long.10,11,12,13,14,15 Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.5 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.5 DB01014 Balsalazide small molecule approved 80573-04-2 357.3175 C17H15N3O6 P37231#Peroxisome proliferator-activated receptor gamma@P35354#Prostaglandin G/H synthase 2@P23219#Prostaglandin G/H synthase 1@P09917#Arachidonate 5-lipoxygenase Balsalazide is a prodrug that has little or no pharmacologic activity until it is enzymatically cleaved in the colon to produce mesalamine (5-aminosalicylic acid), an anti inflammatory drug indicated for the treatment of mildly to moderately active ulcerative colitis. Balsalazide disodium is delivered intact to the colon where it is cleaved by bacterial azoreduction to release equimolar quantities of mesalamine, which is the therapeutically active portion of the molecule, and the intert 4-aminobenzoyl-(beta)-alanine. As a result, the spectrum of pharmacologic activity of balsalazide is similar to that of mesalamine. D0A6KR DB01015 Sulfamethoxazole small molecule approved 723-46-6 253.278 C10H11N3O3S P0AC13#Dihydropteroate synthase Sulfamethoxazole is a bacteriostatic sulfonamide antibiotic that inhibits a critical step in bacterial folate synthesis. It is generally given in combination with trimethoprim, a dihydrofolate reductase inhibitor, which inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid.9 Studies have shown that bacterial resistance develops more slowly with the combination of the two drugs than with either trimethoprim or sulfamethoxazole alone, as together they inhibit sequential steps in the bacterial folate synthesis pathway.9 D0R9OH DB01016 Glyburide small molecule approved 10238-21-8 494.004 C23H28ClN3O5S O60706#ATP-binding cassette sub-family C member 9@O95342#Bile salt export pump@O95477#ATP-binding cassette sub-family A member 1@P50416#Carnitine O-palmitoyltransferase 1, liver isoform@P13569#Cystic fibrosis transmembrane conductance regulator@Q8TD43#Transient receptor potential cation channel subfamily M member 4 Glyburide is a second generation sulfonylurea8 that stimulates insulin secretion through the closure of ATP-sensitive potassium channels on beta cells, raising intracellular potassium and calcium ion concentrations.7 Glibenclamide has a long duration of action as it is given once daily, and a wide therapeutic index as patients are started at doses as low as 0.75mg but that can increase as high as 10mg or more.9,12 Patients taking glyburide should be cautioned regarding an increased risk of cardiovascular mortality as seen with tolbutamide, another sulfonylurea.12 DB01017 Minocycline small molecule approved 10118-90-8 457.4764 C23H27N3O7 P01584#Interleukin-1 beta@P09917#Arachidonate 5-lipoxygenase@P14780#Matrix metalloproteinase-9@P15692#Vascular endothelial growth factor A@P29466#Caspase-1@P42574#Caspase-3@P99999#Cytochrome c@P35228#Nitric oxide synthase, inducible Minocycline is a tetracycline antibiotic that binds to the bacterial 30S ribosomal subunit and interferes with protein synthesis. It is generally given 2-4 times daily, so the duration of action is short.12 Intravenous minocycline should not exceed 400mg in 24 hours.14 Patients should be counselled regarding the risks related to tooth and bone development, pseudomembranous colitis, central nervous system side effects, and pseudotumor cerebri.10 D08LTU DB11056 Stannous chloride small molecule approved 7772-99-8 189.62 Cl2Sn Stannous chloride itself is not known to produce a pharmacological effect at the dosages used clinically. DB11062 Octisalate small molecule approved 118-60-5 250.3334 C15H22O3 Data not found. DB11064 Homosalate small molecule approved 118-56-9 262.349 C16H22O3 P03372#Estrogen receptor@P10275#Androgen receptor@P06401#Progesterone receptor Acts as UV filters. DB11068 Selenic acid small molecule approved 7783-08-6 144.97 H2O4Se Selenium is an essential trace mineral that plays a critical role in antioxidant actions, anti-inflammatory effects, immune function, and the production of active thyroid hormone 1. DB11071 Phenyl salicylate small molecule approved 118-55-8 214.2167 C13H10O3 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Phenyl salicylate has several medical uses. It can be used as an analgesic to relieve pain, as an antiseptic with antibacterial effect as well as a kind of antipyretic for the treatment of fever. It is also used for the treatment of inflammation in the lower urinary tract. It is no longer commonly applied to human medical practice but is still used in veterinary medicine MSDS. DB11072 Hydrogen fluoride small molecule approved 7664-39-3 20.0063 FH Not Available DB11073 Cetylpyridinium small molecule approved 7773-52-6 304.541 C21H38N Cetylpyridinium chloride is considered a cationic disinfectant with properties and uses similar to other such cationic surfactants 5. In particular, cetylpyridinium chloride has demonstrated a rapid bactericidal and fungicide effect on gram-positive pathogens and yeasts, respectively 1. Cetylpyridinium chloride is subsequently utilized in a variety of preparations for the local treatment of minor infections 5. Despite the variety of formulations in which cetylpyridinium chloride may appear as an active ingredient, it is generally accepted that it only elicits a local effect 5 owing to the compound's relatively poor absorption by route of exposure 6. DB11079 Trolamine salicylate small molecule approved 2174-16-5 287.312 C13H21NO6 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Trolamine salicylate is a salicylate that inhibits cyclo-oxygenase (COX) enzymes responsible for generating pro-inflammatory factors such as to induce pain and inflammation. It is thought to mediate its analgesic effect through inhibition of COX-2 enzyme, which is an induced enzyme responsible for inflammatory responses and pain in muscle and joint disorders. By inhibiting fatty acid COX enzyme, trolamine salicylate inhibits the production of prostaglandins and thromboxanes in inflammatory cells involved in generating pain and inflammation 5. It thereby works to temporarily reduce mild to moderate pain. In subjects with muscle soreness from exercise, administration of topical trolamine salicylate was associated with reduced duration and severity of muscule soreness compared to placebo 2. In subjects with osteoarthritis in hands, trolamine salicylate cream was shown to be effective in achieving temporary relief of minor pain and stiffness 1. D0A5CM DB11080 Silver nitrate small molecule approved 7761-88-8 169.8731 AgNO3 Not Available D0A2HR DB11081 Aluminum chloride small molecule approved 7446-70-0 133.341 AlCl3 P00367#Glutamate dehydrogenase 1, mitochondrial Aluminum chloride is a hemostatic and antiperspirant agent. DB11085 Resorcinol small molecule approved 108-46-3 110.1106 C6H6O2 P07202#Thyroid peroxidase In vitro and in vivo studies have demonstrated that resorcinol can inhibit peroxidases in the thyroid and subsequently block the synthesis of thyroid hormones and cause goiter 6,4. Resorcinol interferes with the iodination of tyrosine and the oxidation of iodide 6,4. In an in vitro study involving lactoperoxidase (LPO) and thyroid peroxidase (TPO), it was shown that the mechanism of these two enzymes can become irreversibly inhibited by way of a suicide inactivation by resorcinol 6,4. DB11089 Docusate small molecule approved 10041-19-7 422.577 C20H38O7S Docusate sodium is a laxative and an anionic detergent that supposedly promotes incorporation of water and fats into stool through a reduction in surface tension, resulting in softer fecal mass 7,4. Docusate's onset of action is 6-72 hours orally and 2-15 minutes rectally 7,8. The effects of docusate are thought to be exerted locally in the jejunum1. D0X4FM DB11090 Potassium nitrate small molecule approved 7757-79-1 101.1032 KNO3 Q12809#Potassium voltage-gated channel subfamily H member 2 The potassium cation is an essential electrolyte that is important for the maintenance of intracellular osmotic pressure and for the maintenance of cell membrane potential, in particular, the potential of electrically excitable tissues 7. It is a regular component of the diet and is particularly abundant in fruit and vegetables. The recommended daily intake varies from 350-1275 mg in children to 1875 and 5625 mg in adults. In the United Kingdom, the recommended intake is 3.5 g/day for healthy adults 7. Potassium ions are believed to disturb the synapse between nerve cells, thus decreasing nerve excitation and the associated pain 10. DB11091 Hydrogen peroxide small molecule approved 7722-84-1 34.0147 H2O2 Hydrogen peroxide exhibits antimicrobial properties against most forms of microorganisms, including dormant forms with known high resistance profiles, such as bacterial spores and protozoal cysts. It acts as an oxidative biocide to generate free radical species to induce DNA, protein and membrane lipid damage via oxidation. D03IDU DB11092 Stannous fluoride small molecule approved 7783-47-3 156.71 F2Sn Stannous fluoride mediates both bactericidal and bacteriostatic properties and provides an anti-erosive action on tooth enamel. DB11093 Calcium citrate small molecule approved 813-94-5 498.432 C12H10Ca3O14 P41180#Extracellular calcium-sensing receptor@P27797#Calreticulin@Q99828#Calcium and integrin-binding protein 1@O75340#Programmed cell death protein 6@P30626#Sorcin@Q99653#Calcineurin B homologous protein 1@P09486#SPARC@P27824#Calnexin@P35556#Fibrillin-2@P04271#Protein S100-B Increases plasma calcium levels leading to a decrease in calcium flux and increase in calcium deposition into bone 3 DB11096 Meradimate small molecule approved 134-09-8 275.392 C17H25NO2 Meradimate effect provides a low-level, broad-spectrum protecting coverage effect.3 DB11098 Potassium bicarbonate small molecule approved 298-14-6 100.1151 CHKO3 Potassium is the principal intracellular cation in most body tissues. The concentration of potassium ions is essential to conduct nerve impulses in specialized tissues like brain, heart and skeletal muscle, as well as to maintain normal renal function, acid-base balance, and cellular metabolic functions.9 The use of compounds containing bicarbonate is showed to produce the release of CO2. This effect has been one of the problems of the use of potassium bicarbonate as it can cause eructation.5 DB11100 Allantoin small molecule approved 97-59-6 158.1154 C4H6N4O3 There is no well controlled and appropriate data that can formally substantiate the pharmacodynamic properties of allantoin Label. Nevertheless, ongoing studies suggest that allantoin possesses moisturizing and keratolytic effects, as well as abilities to increase the water content of the extracellular matrix and enhance the desquamation of upper layers of dead skin cells, all of which are activities that can promote cell proliferation and facilitate wound healing 1. D01HNL DB11102 N-acetyltyrosine small molecule approved 537-55-3 223.2252 C11H13NO4 N-acetyltyrosine is used as a high solubility precursor to Tyrosine used due to Tyrosine's poor solubility 2. It is deacetylated to form Tyrosine. DB11104 Sulfur hexafluoride small molecule approved 2551-62-4 146.05 F6S DB11110 Magnesium citrate small molecule approved 3344-18-1 451.113 C12H10Mg3O14 The onset of action can be as early as 30 minutes after administration with a mean onset time of approximately 2 hours and a maximum action of 4 hours. The effect of magnesium citrate is highly dependent on the individual's hydration status.5 DB11115 Ensulizole small molecule approved 27503-81-7 274.29 C13H10N2O3S Ensulizole is a selective UV-B filter with little activity against UV-A wavelengths. In vitro, ensulizole oxidizes guanine bases upon photoexcitation by UV-B and may cause photodamage on DNA, proteins and lipids in the cellular context 1. DB11117 Undecylenic acid small molecule approved 112-38-9 184.2753 C11H20O2 Zinc undecylendate acts as a fungistatic agent but fungicidal activity may be observed with chronic exposure in high concentrations 5. It is effective against Candida albicans 2,3. It is proposed that undecylenic acid exerts antimicrobial actions via interacting with nonspecific components in the cell membrane 4. D0Z5BC DB11119 Sodium iodide small molecule approved 7681-82-5 149.8942 INa When intravenously administered for total parental nutrition, sodium iodide prevents the depletion of endogenous stores of iodine and subsequent deficiency symptoms 2. DB11121 Chloroxylenol small molecule approved 88-04-0 156.61 C8H9ClO Chloroxylenol is a substituted phenol which has been widely used for many years as an ingredient of antiseptic and disinfectant products intended for external use 9. It is known to be bactericidal in low concentration to a wide range of Gram positive and Gram negative bacteria 9. DB11123 Hypochlorite small molecule approved 14380-61-1 51.452 ClO DB11125 Benzethonium small molecule approved 10172-60-8 412.637 C27H42NO2 Benzethonium belongs to the family of compounds known as cationic detergents that act by disrupting lipid bilayers. It demonstrated antitumor activity against cancer cell lines in vitro. The effective dose required to decrease cell viability by 50% after 48 hours (ED50) of benzethonium for FaDu (hypopharyngeal squamous cancer) and C666-1 (nasopharyngeal cancer) cell lines were approximately 3.8 and 5.3 μmol/L, respectively 1. DB11126 Calcium gluconate small molecule approved 299-28-5 430.372 C12H22CaO14 Calcium Gluconate is the gluconate salt of calcium. An element or mineral necessary for normal nerve, muscle, and cardiac function, calcium as the gluconate salt helps to maintain calcium balance and prevent bone loss when taken orally. This agent may also be chemopreventive for colon and other cancers. DB11127 Selenious acid small molecule approved 7783-00-8 128.97 H2O3Se Selenium is a component glutathione peroxidase, which protects cells from oxidative damage caused by peroxidases produced during cellular metabolism 8. DB11129 Carbamide peroxide small molecule approved 124-43-6 94.07 CH6N2O3 Carbamide peroxide releases hydrogen peroxide and free radicals upon contact with water or outer surfaces of ear and tooth. Hydrogen peroxide exerts cerumenolytic, enamel-bleaching and antiseptic actions. In vitro, the chemical stability of ceramics against bleaching agents was observed after treatment with 15% carbamide peroxide for 56 h, 16% carbamide peroxide for 126 h, 10% or 15% carbamide peroxide and 38% hydrogen peroxide for 30 minutes or 45 minutes, respectively 1. According to in vitro studies, high (37%) or low (10 or 16%) concentrated carbamide peroxide agents were similarly effective as oral bleaching agents 2. Treatment with carbamide peroxide may lead to demineralization which involves decreased mineral content of enamel calcium, phosphate, and fluoride, and alteration of the chemical, structural, and mechanical properties 3. Carbamide peroxide may affect the organic components of the enamel and lead to increased susceptibility to erosion, fracture stability or decreased abrasion resistance of the treated area 3. D01BQK DB11132 Silicon dioxide small molecule approved 7631-86-9 60.0843 O2Si Q9UEW3#Macrophage receptor MARCO Not Available DB11134 Cupric oxide small molecule approved 1317-38-0 79.545 CuO For pharmacodynamic information of copper, refer to drug entry for Copper. Copper(II) oxide nanoparticles are known to generate reactive oxygen species (ROS), leading to cytotoxicity 1. In a comparative toxicity assay, nanoparticles caused significant mitochondrial depolarization leading to DNA damage 1. In the human skin organ culture study, topical application of copper oxide (CuO) nanoparticles induced inflammatory cytokine secretion and necrosis in vitro, indicating that the nanoparticles may adhere to the skin surface and react with the local acidic environment 2. DB11135 Selenium small molecule approved 7782-49-2 78.96 Se Selenium is incorporated into many different selenoproteins which serve various functions throughout the body 1. DB11136 Chromium small molecule approved 7440-47-3 51.9961 Cr P00167#Cytochrome b5 Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Chromium increases insulin binding to cells, increases insulin receptor density and activates insulin receptor kinase leading to enhanced insulin sensitivity 2. In chromium deficiency, intravenous administration of chromium resulted in normalization of the glucose tolerance curve from the diabetic-like curve typical of chromium deficiency Label. DB11137 Molybdenum small molecule approved 7439-98-7 95.94 Mo Not Available DB11140 Chromium Cr-51 small molecule approved 14392-02-0 50.9448 Cr Not Available DB11141 Manganese gluconate small molecule approved 6485-39-8 445.232 C12H22MnO14 Manganese gluconate is a salt which dissociates in body fluids to form manganese and gluconic acid. Its pharmacological effects are due to the normal role of Manganese in the body. DB11142 Selenomethionine small molecule approved 3211-76-5 196.11 C5H11NO2Se Not Available DB11145 Oxyquinoline small molecule approved 148-24-3 145.158 C9H7NO Oxyquinoline acts as a biocide to eliminate bacteria and fungi 1. DB11148 Butamben small molecule approved 94-25-7 193.246 C11H15NO2 O75762#Transient receptor potential cation channel subfamily A member 1@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@Q01668#Voltage-dependent L-type calcium channel subunit alpha-1D@Q13698#Voltage-dependent L-type calcium channel subunit alpha-1S@O00305#Voltage-dependent L-type calcium channel subunit beta-4@Q00975#Voltage-dependent N-type calcium channel subunit alpha-1B@O00555#Voltage-dependent P/Q-type calcium channel subunit alpha-1A@Q15878#Voltage-dependent R-type calcium channel subunit alpha-1E@Q9HBA0#Transient receptor potential cation channel subfamily V member 4 Butamben has been shown to selectively inhibit dorsal root pain signal transmission for periods of months when administered as epidural suspensions.1 The effect of butamben is not related to any significant loss of motor function which indicates that it targets specifically the pain-sensing C fibers of the dorsal root.3 When administered topically, butamben produced anesthesia by accumulating in the nerve cell membrane causing it to expand and lose its ability to depolarize and blocking the impulse transmission.5 DB11150 Barium sulfate small molecule approved 7727-43-7 233.39 BaO4S Barium sulfate increases the absorption of x-rays as they are passed throughout the body, delineating body structures, in which barium sulfate is localized. This allows for the clear visualization of normal organs/defect in normal anatomy 5. D0T5DE DB11151 Sodium hydroxide small molecule approved 1310-73-2 39.9971 HNaO Sodium Hydroxide 10% forms a strongly alkaline and caustic solution. As a caustic agent, it is used to destroy organic tissue by chemical action 4. DB11153 Potassium hydroxide small molecule approved 1310-58-3 56.1056 HKO The corrosiveness of potassium hydroxide renders it a very useful agent in the decomposition/removal soft tissue and hair removal. It is incorporated into some nail products, shaving creams, and soaps 13. DB11155 Triclocarban small molecule approved 101-20-2 315.58 C13H9Cl3N2O Q6GI75#Enoyl-[acyl-carrier-protein] reductase [NADPH] FabI The antimicrobial mechanism underlying the bacteriostatic and bactericidal effects of triclocarban is believed to be an unspecific adsorption to cell membranes and interruption of their function. As a result, the growth of gram-positive as well as gram-negative bacteria is inhibited 15. DB11156 Pyrantel small molecule approved 15686-83-6 206.31 C11H14N2S Q9HC97#G-protein coupled receptor 35@P11229#Muscarinic acetylcholine receptor M1 It has similar properties to both competitive and depolarizing neuromuscular blocking agents, which leads to the understanding of the paralytic effect of the drug has on parasites, ultimately resulting in the death of the parasite 16, 8. D03PTH DB11157 Anthralin small molecule approved 1143-38-0 226.231 C14H10O3 P35908#Keratin, type II cytoskeletal 2 epidermal@Q99456#Keratin, type I cytoskeletal 12@Q9UQF2#C-Jun-amino-terminal kinase-interacting protein 1 Anthralin is a natural anthraquinone derivative, anti-psoriatic and anti-inflammatory agent. It controls skin growth by reducing the synthesis of DNA and the mitotic activity in the hyperplastic epidermis, normalizing the rate of cell proliferation and keratinization 10. DB11159 Sodium sulfide small molecule approved 1313-82-2 78.04 Na2S Not Available DB11160 Phenyltoloxamine small molecule approved 92-12-6 255.361 C17H21NO P70174#Histamine H1 receptor As a member of the first generation H1 antihistamines, it is known that phenyltoloxamine - like virtually all first generation H1 antihistamines - has a propensity for crossing the blood-brain barrier and acting on H1 histamine receptors there to interfere with neurotransmission 1. The most common results of this kind of first generation H1 antihistamine CNS neurotransmission interference are adverse effects like drowsiness, sedation, somnolence, and fatigue 1. Given these effects, under specific circumstances like a patient experiencing a pain or a cough that may be preoccupying all of their waking energy and attention, it is perhaps possible that the sedative and tranquilizing characteristics of phenyltoloxamine may be the factors that contribute to its apparent adjunctive analgesic 3,4 and antitussive actions 8,2. D0KS6W DB11164 Bicisate small molecule approved 121251-02-3 324.45 C12H24N2O4S2 The neutral and lipophilic nature of bicisate provides it with high stability. This property is given by its N2S2 core. This characteristic has been proven to allow bicisate to be used even several hours after preparation and to present an easy passage through the blood-brain barrier.4 DB11168 Calcium threonate small molecule approved 70753-61-6 310.268 C8H14CaO10 DB11171 Ferric sulfate small molecule approved 10028-22-5 489.93 Fe2H10O17S3 The administration of ferric sulfate as a dermatologic agent has showed delayed reepithelialization and dyspigmentation. Some studies have reported the generation of inflammation in the sites of administration of ferric sulfate.2 DB11176 Zeaxanthin small molecule approved 144-68-3 568.886 C40H56O2 Not Available DB11180 Tetrofosmin small molecule approved 127502-06-1 382.462 C18H40O4P2 Refer to Technetium Tc-99m tetrofosmin DB11181 Homatropine small molecule approved 87-00-3 275.348 C16H21NO3 P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5 Homatropine is an anticholinergic drug that produces typical anticholinergic effects inducing mydriasis and cycloplegia. Other effects of structurally-related atropine that could also apply to homatropine include inhibition of secretions, tachycardia, relaxation of smooth muscle and central nervous effects including excitation 1. DB11182 Rose bengal small molecule approved 973.673 C20H4Cl4I4O5 Rose bengal is a staining agent that visualized ocular surfaces of both diseased and dead cells in vivo 2. It has also shown to stain healthy cultured cells, including rabbit corneal epithelial cells, in a rapid, dose-dependent manner 3. Various studies demonstrate the cytotoxic effects of rose bengal in different cell cultures, including smooth-muscle cells from human intestine, endothelial cells from bovinepulmonary artery, rabbit Tenon fibro-blasts, and rabbit and human corneal epithelial cells 2. Cellular morphological changes such as detachment, separation, loss of motility and disruption, in addition to swelling, intracytoplasmic vacuole formation and lysis have been manifested with the treatment of rose bengal 2, indicating that rose Bengal is not a vital dye. DB11183 Light green SF yellowish small molecule approved 5141-20-8 792.848 C37H34N2Na2O9S3 Not Available DB11184 Oftasceine small molecule approved 1461-15-0 622.539 C30H26N2O13 Not Available DB11186 Pentoxyverine small molecule approved 77-23-6 333.472 C20H31NO3 Q12809#Potassium voltage-gated channel subfamily H member 2@P41145#Kappa-type opioid receptor@Q99250#Sodium channel protein type 2 subunit alpha@Q14524#Sodium channel protein type 5 subunit alpha DB11189 Magnesium glycinate small molecule approved 14783-68-7 172.423 C4H8MgN2O4 Not Available DB11190 Pantethine small molecule approved 16816-67-4 554.721 C22H42N4O8S2 Not Available DB11191 Cobamamide small molecule approved 13870-90-1 1579.5818 C72H100CoN18O17P Not Available DB11197 Ferrous cysteine glycinate small molecule approved 371.2 C8H17FeN3O6S2 Not Available DB11200 Aluminum zirconium octachlorohydrex gly small molecule approved 174514-58-0 263.74 C2H8AlClNO4Zr Reduces perspiration and body odor 8. DB11201 Menthyl salicylate small molecule approved 89-46-3 276.376 C17H24O3 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Menthol and methyl salicylate are known as counterirritants. They work by causing the skin to feel cool and then warm. Used together, they provide symptomatic relief for mild to moderate muscular and joint aches and pains, muscle cramps, shoulder aches and stiff neck.2. DB11205 Alcloxa small molecule approved 1317-25-5 314.55 C4H9Al2ClN4O7 Not Available DB11206 Bemotrizinol small molecule approved 187393-00-6 627.826 C38H49N3O5 Findings from an immature rat uterotrophic competitive binding assay suggest that bemotrizinol does not display significant binding affinities towards estrogen and androgen receptors in vitro, thus lacking intrinsic estrogenic, antiestrogenic, androgenic and antiandrogenic activity 1. Bemotrizinol minimizes erythema and provides excellent anti-aging effects as well as protectant effects on the skin's antioxidant defense system 2. In a comparative study of individuals with a history of polymorphic light eruption (PLE) undergoing photoprovocation, treatment of bemotrinizol was effective in preventing the development of PLE 4. DB11207 Amiloxate small molecule approved 71617-10-2 248.322 C15H20O3 In a mouse study, amiloxate exerted a dose-dependent anti-inflammatory action and inhibited edema by about 70% even at a low dose 1. Due to structural similarities, amiloxate may also display antioxidant and antimicrobial properties of cinnamic acid 2. DB11210 Ferrous bisglycinate small molecule approved 20150-34-9 203.963 C4H8FeN2O4 Not Available DB11217 Arbutin small molecule approved 497-76-7 272.2512 C12H16O7 P14679#Tyrosinase At non-toxic concentrations, arbutin inhibited the activity of tyrosinase in cultured human keratinocytes, while having minimal effect on the expression of tyrosinase mRNA or the synthesis of the enzyme 1. α-Arbutin produced a concentration-dependent inhibition of melanin synthesis of human melanoma cells, HMV-II 3. No inhibitory effect on HMV-II cell growth was seen at concentrations lower than 1.0 mM. At concentrations of 0.5 mM of arbutin, tyrosinase activity was reduced to 60% of that in non-treated cells 3. The addition of arbutin blocked and inhibited α-MSH-stimulated melanogenesis in B16 melanoma cells, brownish guinea pig, and human skin tissue 4. In a pilot study of healthy male adults exposed to UV B irradiation, topical administration of arbutin inhibited UV-induced nuclear factor-kappaB activation in human keratinocytes 6. In mouse skin, arbutin counteracted oxidative stress induced by 12-O-tetradecanoylphorbol-13-acetate 6. DB11219 Enzacamene small molecule approved 36861-47-9 254.373 C18H22O P03372#Estrogen receptor@P10275#Androgen receptor@P06401#Progesterone receptor@Q92731#Estrogen receptor beta Several studies suggest that enzacamene elicit estrogen-like effects. In prepubertal male rats exposed to enzacamene during embryonic and fetal development, decrease in testicular weight with decreased levels of LH, GnRH, and glutamate were observed; in comparison, there was an increase in LH, GnRH, and aspartate levels in peripubertal rats 2. These findings suggest that high concentrations of enzacamene during embryonic and fetal stage inhibits the testicular axis in male rats during the prepubertal stage and stimulates it during peripubertad stage 2. In a study of zebrafish (Danio rerio) embryo, exposure to enzacamene during early vertebrate development was associated with muscular and neuronal defects that may result in developmental defects, including a reduction in AChE activity, disorganized pattern of slow muscle fibers, and axon pathfinding errors during motor neuron innervation 5. Enzacamene displays a weak binding activity in receptors binding assays using the mammalian estrogen receptor (ER) 4. DB11221 Dioxybenzone small molecule approved 131-53-3 244.246 C14H12O4 P04278#Sex hormone-binding globulin Dioxybenzone is a sunscreen agent and chemical UV filter that absorbs UV-B rays and UV-AII rays to limit their penetration into human skin. In a screening protocol consisting of the in vitro EBV-EA activation assay followed by the in vivo confirmation test in the two-stage mouse skin cancer model utilizing NOR-1 as inducer and TPA as promoter of tumour, dioxybenzone exhibited a significant chemopreventive activity against mouse skin carcinogenesis which correlated with their antioxidant potency 2. There is some evidence that suggests some benzophenones and their hydroxylated metabolites act as weak estrogens in the environment; however similar effect of dioxybenzone has not been established 5. DB11226 Ethylhexyl methoxycrylene small molecule approved 947753-66-4 391.511 C25H29NO3 As an active ingredient in topical sunscreen products, ethylhexyl methoxycrylene is applied directly onto human skin where it acts as a critical component for conferring photostability to the product's other constituent ingredients, protecting the product as a whole from deterioration in the sunlight 3. Additionally, considering the high log Pow value (6.05-6.32) and low water solubility, dermal absorption of ethylhexyl methoxycrylene is expected to be low. This is supported by a dermal absorption of less than 5% observed for an acceptable analogue of the notified chemical 4. Consequently, little systemic exposure and pharmacokinetics are expected and users can freely wash off and re-apply ethylhexyl methoxycrylene containing compounds as necessary. DB11231 Lycopene small molecule approved 502-65-8 536.888 C40H56 Not Available DB11235 Thonzylamine small molecule approved 91-85-0 286.379 C16H22N4O P70174#Histamine H1 receptor@P11229#Muscarinic acetylcholine receptor M1@P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3@P08173#Muscarinic acetylcholine receptor M4@P08912#Muscarinic acetylcholine receptor M5 Thonzylamine is a first-generation antihistamine. It antagonizes the action of histamine to relief allergic symptoms like nasal congestion, runny nose, itchy eyes, itchy nose and throat, and sneezing Label,1 DB11239 Aluminum sulfate small molecule approved 10043-01-3 342.151 Al2O12S3 Aluminum sulfate may be used as a deodorant, as well as an astringent 19. Aluminum sulfate is also known as an astringent. Astringents are substances that cause contraction or shrinkage of tissues and that dry up secretion 19. DB11246 Copper gluconate small molecule approved 527-09-3 453.841 C12H22CuO14 Not Available DB11248 Zinc gluconate small molecule approved 4468-02-4 455.67 C12H22O14Zn Zinc is an important mineral found in almost every cell in the human body. It promotes the activity of about 100 enzymes. Zinc deficiency is often associated with an increased risk of infection. When they are used to treat the common cold, zinc supplements may interfere with rhinovirus cleavage or adhesion and may play a role in protecting plasma membranes from microbial toxins and complement 13. DB11254 Hexylresorcinol small molecule approved 136-77-6 194.2701 C12H18O2 Q06AK7#DNA topoisomerase 1@P21980#Protein-glutamine gamma-glutamyltransferase 2@P14679#Tyrosinase Hexylresorcinol is a phenol derivative, and in typical therapeutic usage is primarily a local anesthetic for topical use on the mucous membranes of the mouth and throat 9. The local anesthetic like properties of hexylresorcinol is likely due to its sodium channel blocking effects 9. The agent also demonstrates mild antiseptic activity as well as an apparent anti-inflammatory, demulcent action 9. DB11255 Chromium picolinate small molecule approved 14639-25-9 418.3005 C18H12CrN3O6 Not Available DB11256 Levomefolic acid small molecule approved 31690-09-2 459.4558 C20H25N7O6 Levomefolic acid is an active metabolite of folic acid and a methyl group donor in one-carbon metabolism reactions. It regulates important cellular functions such as DNA biosynthesis, gene expression regulation, amino acid synthesis and metabolism, and myelin synthesis and repair. As a only form of folate that can cross the blood-brain barrier, it acts as a cofactor in the production of monoamine neurotransmitters such as dopamine, serotonin and norepinephrine 6. Levomefolic acid is also involved in red blood cell formation 11. DB11257 Fluoride ion small molecule approved 16984-48-8 18.9984 F DB11260 Diacetyl benzoyl lathyrol small molecule approved 218916-52-0 522.638 C31H38O7 Not Available DB11262 Bisoctrizole small molecule approved 103597-45-1 658.891 C41H50N6O2 Under the conditions of in vitro androgen competitive binding assay, bisoctrizole displayed no intrinsic androgenic, estrogenic, nor uterotrophic activity 2. DB11263 Polydatin small molecule approved 27208-80-6 390.388 C20H22O8 P14618#Pyruvate kinase PKM Not Available DB11264 Calcium glycerophosphate small molecule approved 27214-00-2 210.135 C3H7CaO6P It is thought that calcium glycerophosphate may act through a variety of mechanisms to produce an anti-caries effect 2. These include increasing acid-resistance of the enamel, increasing enamel mineralization, modifying plaque, acting as a pH-buffer in plaque, and elevating Calcium and phosphate levels. DB11269 Diethylamino hydroxybenzoyl hexyl benzoate small molecule approved 302776-68-7 397.515 C24H31NO4 Diethylamino hydroxybenzoyl hexyl benzoate is an organic UV filter that attenuates the exposure of UV radiation on human skin 2. In vitro, topical application of diethylamino hydroxybenzoyl hexyl benzoate exerted an anti-inflammatory effect on inflammation-evoked mouse ears by inhibiting oedema formation 3. DB11273 Dihydroergocornine small molecule approved 25447-65-8 563.699 C31H41N5O5 P28222#5-hydroxytryptamine receptor 1B@P41595#5-hydroxytryptamine receptor 2B@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor It is reported that dihydroergocornine administration, in non-toxic doses, presents sympatholytic and hypotensive properties which are observed as a significantly decreased mean arterial pressure.2 In the brain, the activity of dihydroergocornine was observed as a decrease in cerebral blood flow, cerebral vascular resistance and oxygen uptake. The effect in the brain seems to allow a cerebral metabolic homeostasis.1 To know more about the pharmacology please visit Ergoloid mesylate DB11274 Dihydro-alpha-ergocryptine small molecule approved 25447-66-9 577.726 C32H43N5O5 P35462#D(3) dopamine receptor@P14416#D(2) dopamine receptor@P21728#D(1A) dopamine receptor The effect of alpha-dihydroergocryptine in dopamine receptors was tested in PD patients and seem to generate a significant clinical improvement in the tested patients as well as to reduce motor complications and side effects.2 In long-term clinical trials with Parkinson disease patients, the administration of alpha-dihydroergocryptine and levodopa, the symptoms were reposted to improve or completely vanish in 80% of the tested individuals.8 All the registered effects of alpha-dihydroergocryptine suggest a potential neuroprotective effect of this drug and some reports have indicated that this activity may be related to the activation of NF-kB.10 The effect of alpha-dihydroergocryptine in the dopamine D2 receptor also reduces prolactin plasma levels and induce hypotension.9 To know more about the ergoloid mesylate mixture please visit Ergoloid mesylate. DB11275 Epicriptine small molecule approved 88660-47-3 577.726 C32H43N5O5 P21728#D(1A) dopamine receptor@P14416#D(2) dopamine receptor@P35462#D(3) dopamine receptor Please refer to Ergoloid mesylate and to know more about the isomer please refer to Dihydro-alpha-ergocryptine. DB11278 DL-Methylephedrine small molecule approved 1201-56-5 179.263 C11H17NO P08588#Beta-1 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P08588#Beta-1 adrenergic receptor@P07550#Beta-2 adrenergic receptor@P13945#Beta-3 adrenergic receptor@P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor This drugs acts as an antitussive, bronchodilator, and adrenergic receptor agonist 5. It stimulates the alpha and beta adrenergic receptors, relieving cough and congestion 5. DB11279 Brilliant green cation small molecule approved 18198-35-1 385.574 C27H33N2 Not Available DB11282 Diethyltoluamide small molecule approved 134-62-3 191.2695 C12H17NO When used appropriately, diethyltoluamide (DEET) containing products are designed to be applied directly to people's skin as a means to elicit a repelling action to keep insects from targeting human skin 5. At the amounts and doses recommended for use on human children and adults, noticeable absorption or systemic exposure is not expected 5,6. Owing to the proportional difference in size between humans and insects, however, the exposure of insects to the applied DEET (whether topically or via inhalation of DEET) is expected to be enough to interfere with the insects' sensory attraction to human skin 5,6. DB11283 DL-dimyristoylphosphatidylcholine small molecule approved 18656-38-7 677.945 C36H72NO8P DL-dimyristoylphosphatidylcholine is a water soluble phospholipid used to solubilize drugs for injection 1. DB11284 DL-dimyristoylphosphatidylglycerol small molecule approved 61361-72-6 666.874 C34H67O10P DL-dimyristoylphosphatidylglycerol is a water soluble phospholipid used to solubilize drugs for injection 1. DB11285 Ethyl ferulate small molecule approved 4046-02-0 222.2372 C12H14O4 Not Available DB11299 Vanillyl butyl ether small molecule approved 82654-98-6 210.2695 C12H18O3 Not Available DB11304 Phenoxyethanol small molecule approved 122-99-6 138.166 C8H10O2 This substance has broad-spectrum antimicrobial activity against bacteria, yeasts, and mold 6. DB11315 Methscopolamine small molecule approved 13265-10-6 318.392 C18H24NO4 Methscopolamine bromide is an anticholinergic agent which possesses most of the pharmacologic actions of that drug class. These include reduction in volume and total acid content of gastric secretion, inhibition of gastrointestinal motility, inhibition of salivary excretion, dilation of the pupil and inhibition of accommodation with resulting blurring of vision. Large doses may result in tachycardia [Dailymed]. DB11323 Glycol salicylate small molecule approved 87-28-5 182.175 C9H10O4 P23219#Prostaglandin G/H synthase 1@P35354#Prostaglandin G/H synthase 2 Temporarily relieves minor to moderate aches and pains 12. Works with ingredients such as menthol, which has counter-irritant properties 13. Counter-irritants are externally applied, and lead to irritation or mild inflammation of the skin to relieve pain in muscles or joints by reducing inflammation in deeper adjacent structures 19. Counter-irritants relieve pain by disrupting the brain from receiving pain signals resulting from conditions such as osteoarthritis (OA) or injuries such as sprains or strains. These agents may cause vasodilatation or skin irritation, leading to a false sensation of heat or warmth 18. DB11326 Boric acid small molecule approved 10043-35-3 61.833 BH3O3 Boric acid exhibits minimal bacteriostatic and antifungal activities 4. Boric acid is likely to mediate antifungal actions at high concentrations over prolonged exposures 3. D08NNW DB11327 Dipyrithione small molecule approved 3696-28-4 252.31 C10H8N2O2S2 P35228#Nitric oxide synthase, inducible@P35354#Prostaglandin G/H synthase 2 This drug decreases or eliminates dandruff from the scalp, which is caused by various types of fungi.6, 9 DB11328 Tetradecyl hydrogen sulfate (ester) small molecule approved 300-52-7 294.45 C14H30O4S Q9UNN8#Endothelial protein C receptor Telangiectasias or varicose veins occur in about 33% of adult women and about 15% of adult men. Sclerotherapy with sotradecol is widely used in the treatment of varicose veins 7. DB11331 1-Palmitoyl-2-oleoyl-sn-glycero-3-(phospho-rac-(1-glycerol)) small molecule approved 185435-28-3 749.02 C40H77O10P Palmitoyloleoyl-phosphatidylglycerol is a replacement surfactant which prevents alveolar collapse when administered intratracheally. DB11332 Sinapultide small molecule approved 138531-07-4 2469.45 C126H238N26O22 Windtree’s KL4 surfactant technology produces a synthetic surfactant that is structurally similar to human pulmonary surfactant and contains a proprietary synthetic peptide KL4 (sinapultide), cost a 21-amino acid peptide that is formulated to mimic the essential attributes of the human surfactant protein B (SP-B). This protein is one of four surfactant proteins and is the most important for the adequate function of the respiratory system. Windtree has demonstrated in pre-clinical studies that KL4 surfactant may possess certain other beneficial properties, including alteration of the inflammatory process, antimicrobial properties as well as non-immunogenicity 10. DB11336 Kinetin small molecule approved 525-79-1 215.2114 C10H9N5O Not Available D03OIW DB11340 Ubiquinol small molecule approved 992-78-9 865.3594 C59H92O4 Not Available DB11342 Aluminum oxide small molecule approved 1344-28-1 101.96 Al2O3 Not Available DB11343 Silanol small molecule approved 70131-67-8 48.116 H4OSi Not Available DB11346 Rubidium small molecule approved 7440-17-7 85.4678 Rb Not Available DB11348 Calcium Phosphate small molecule approved 10103-46-5 310.177 Ca3O8P2 P41180#Extracellular calcium-sensing receptor@P27797#Calreticulin@Q99828#Calcium and integrin-binding protein 1@O75340#Programmed cell death protein 6@P30626#Sorcin@Q99653#Calcineurin B homologous protein 1@P09486#SPARC@P27824#Calnexin@P35556#Fibrillin-2@P04271#Protein S100-B Calcium phosphate reacts with acid in the stomach to raise the pH 3. In toothpaste it provides a source of calcium and phosphate ions to support remineralization of the teeth 1. As a supplement it provides a source of calcium and phospate, both of which are important ions in bone homeostasis. DB11359 Guaiacol small molecule approved 90-05-1 124.139 C7H8O2 P02768#Serum albumin Not Available DB11362 Selexipag small molecule approved 475086-01-2 496.63 C26H32N4O4S D0N2SR DB11363 Alectinib small molecule approved 1256580-46-7 482.6166 C30H34N4O2 Q9UM73#ALK tyrosine kinase receptor Not Available D0U3SY DB11386 Chlorobutanol small molecule approved 57-15-8 177.45 C4H7Cl3O Q12809#Potassium voltage-gated channel subfamily H member 2 Chlorobutanol is a detergent preservative with a broad spectrum of antimicrobial activity 4. In vitro, chlorobutanol demonstrated to inhibit platelet aggregation and release via unknown mechanisms 1. A study proposes that the antiplatelet effect of chlorobutanol may occur from inhibition of the arachidonic acid pathway 1. It attenuated thromboxane B2 formation, elevation of cytosolic free calcium, and ATP release, and additionally exhibited a significant inhibitory activity toward several aggregation inducers in a time- and concentration-dependent manner 1. Chlorobutanol may exert a direct negative inotropic effect on myocardial cells to isometric tension produced by the heart 2. Chlorobutanol was shown to induce conjunctival and corneal cell toxicity in vitro: at a concentration of 0.1%, Cbl caused near depletion of the squamous layer while degeneration of corneal epithelial cells, generation of conspicuous membranous blebs, cytoplasmic swelling, and occasional breaks in the external cell membrane were observed at a concentration of 0.5% 4. DB11387 Chloroform small molecule approved 67-66-3 119.378 CHCl3 Not Available DB11431 Moxidectin small molecule approved 113507-06-5 639.83 C37H53NO8 Q25634#Glutamate-gated chloride channel Moxidectin has been reported to be highly effective against Onchocerca volvulus when compared to ivermectin.3 When moxidectin was administered in infected individuals, the microfilarial load in the skin was lower even when compared to the current therapy, ivermectin. The levels of microfilarial got reduced to an undetectable level while being safe to be used in mass drug administration.9 D05AWP DB11496 2-mercaptobenzothiazole small molecule approved 149-30-4 167.251 C7H5NS2 P07202#Thyroid peroxidase Not Available DB11512 Dihydrostreptomycin small molecule approved 128-46-1 583.596 C21H41N7O12 Not Available DB11560 Lesinurad small molecule approved 878672-00-5 404.28 C17H14BrN3O2S Q96S37#Solute carrier family 22 member 12@Q9NSA0#Solute carrier family 22 member 11 Dose-dependent reductions in serum uric acid levels and increases in urinary uric acid excretion have been observed following single and multiple oral doses of lesinurad. D0C3SW DB11570 Padimate O small molecule approved 21245-02-3 277.408 C17H27NO2 Padimate O absorbs UV-B rays, which can in turn induce DNA damage in human keratinocytes. While treatment of padimate O suppresses the formation of UV-endonuclease-sensitive sites, there is also an increase in direct strand breaks of DNA in cells 1,2. DB11573 Aluminum chlorohydrate small molecule approved 12359-72-7 192.46 Al2ClH7O6 Aluminum chlorohydrate serves to reduce excessive sweating by directly blocking the sweat ducts 4. DB11574 Elbasvir small molecule approved 1370468-36-2 882.035 C49H55N9O7 Q5L478#Nonstructural protein 5A Elbasvir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotypes 1a, 1b, and 4.7 DB11575 Grazoprevir small molecule approved 1350514-68-9 766.903 C38H50N6O9S Grazoprevir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotypes 1a, 1b, and 4 Label. DB11577 Indigotindisulfonic acid small molecule approved 483-20-5 422.389 C16H10N2O8S2 P08913#Alpha-2A adrenergic receptor@P18089#Alpha-2B adrenergic receptor This drug dyes tissues blue, enabling easier visualization for accuracy during medical procedures 5. DB11581 Venetoclax small molecule approved 1257044-40-8 868.45 C45H50ClN7O7S P10415#Apoptosis regulator Bcl-2 Venetoclax induces rapid and potent onset apoptosis of CLL cells, powerful enough to act within 24h and to lead to tumor lysis syndrome 5, Label, 2. Selective targeting of BCL2 with venetoclax has demonstrated a manageable safety profile and has been shown to induce significant response in patients with relapsed CLL (chronic lymphocytic leukemia) or SLL (small lymphocytic leukemia), including patients with poor prognostic features 6. This drug is not expected to have a significant impact on the cardiac QT interval Label. Venetoclax has demonstrated efficacy in various types of lymphoid malignancies, including relapsed/ refractory CLL harboring deletion 17p, with an overall response rate of approximately 80% 7. DB11583 Cetalkonium small molecule approved 10328-34-4 360.649 C25H46N Cetalkonium is an antimicrobial agent and it has shown to be effective against both gram-positive, gram-negative bacteria and fungi. From this property, it has been shown to present a better activity against the gram-negative organisms.11 DB11584 Pipradrol small molecule approved 467-60-7 267.372 C18H21NO P21728#D(1A) dopamine receptor Pipradrol (Meratran) is a psychoactive agent and a central nervous system stimulant that has proven useful in the field of psychiatry 10. DB11585 Drometrizole trisiloxane small molecule approved 155633-54-8 501.849 C24H39N3O3Si3 As an active ingredient in sunscreen products, drometrizole trisiloxane is applied directly onto human skin where it acts as a chemical sunscreen layer between skin and sunlight that also directly absorbs the UV sunlight radiation 1,3,4,5,6,9. Since drometrizole trisiloxane is also considered to have little to no absorption through the skin 1,3,4,5,6,9, little systemic exposure and pharmacokinetics are expected and users can freely wash off and re-apply the compound as necessary. DB11586 Asunaprevir small molecule approved 630420-16-5 748.286 C35H46ClN5O9S P26663#Genome polyprotein Studies in vitro demonstrated a significant antiviral activity in HCV replicon cell systems with an EC50 of 4nm and 1nm against the HCV genotype 1a and 1b respectively.2 These studies showed a limited activity against the genotypes 2 and 3. This property makes asunaprevir a highly selective anti-HCV agent that is not effective against HCV closely related virus.3 Asunaprevir produce robust declines in HCV RNA levels in patients with HCV genotype 1 infection.1In clinical studies, it has been shown that asunaprevir is well-tolerated and the mean maximum HCV RNA level reduction from baseline was of approximately 2.87 log10 IU/ml.2 DB11587 Etafedrine small molecule approved 48141-64-6 193.29 C12H19NO P07550#Beta-2 adrenergic receptor Etafedrine helps to control the cough which is associated with irritation of the mouth and throat that is not alleviated by cough medications that are less strong 7. DB11588 Carbon monoxide small molecule approved 630-08-0 28.01 CO P02144#Myoglobin Carbon monoxide is used to measure the diffusing capacity for carbon monoxide (DLCO), also known as the transfer factor for carbon monoxide. It is a measure of the gas transfer from inspired gas to the circulatory system (red blood cells in particular) 28. It is used in a particular pulmonary function test called "the single-breath test" 32. D0F5LB DB11589 Neon small molecule approved 7440-01-9 20.1797 Ne A study demonstrated that neon beam radiotherapy improved the 5-year actuarial disease-specific survival rate and local control in patients with paranasal sinus tumours, macroscopic salivary gland tumours, bile duct carcinomas, macroscopic soft tissue and bone sarcomas, and advanced prostate carcinomas 1. DB11590 Thimerosal small molecule approved 54-64-8 404.81 C9H9HgNaO2S Q99707#Methionine synthase@Q9UPY5#Cystine/glutamate transporter@P54710#Sodium/potassium-transporting ATPase subunit gamma Thimerosal is an organomercurial compound and derivative of thiosalicyclic acid with antibacterial and antifungal properties 5. Thimerosal, which consists of approximately 50% mercury by weight, has been one of the most widely used preservatives in vaccines. It is metabolized/degraded to ethylmercury and thiosalicylate. Ethylmercury is an organomercurial that must be carefully distinguished from methylmercury, a closely related substance that has been the focus of many studies. Methylmercury is the type of mercury found in various species of fish 21. Experimental data demonstrates that the toxicokinetics of thimerosal (ethylmercury) is vastly different from that of methyl-mercury. Thus, methyl-mercury is not a suitable reference for assessing the risk from exposure to thimerosal-derived mercury 24. DB11591 Bilastine small molecule approved 202189-78-4 463.622 C28H37N3O3 P70174#Histamine H1 receptor Bilastine is an antiallergenic and acts to reduce allergic symptoms such as nasal congestion and urticaria Label. DB11594 Domiphen small molecule approved 13900-14-6 334.567 C22H40NO The efficacy and tolerability of domiphen bromide (domifen bromide), administered at a dosage of 0.5 mg every 4-6 hr in a double-blind placebo controlled study in 31 patients affected by acute infectious dental diseases, are described. After 2 days of treatment with the drug, there was a significant decrease in pain and inflammation. The drug elicited a good response, improved prognosis and reduced the number of days of illness. DB11596 Levoleucovorin small molecule approved 68538-85-2 473.4393 C20H23N7O7 Q53ET4#Serine hydroxymethyltransferase Levoleucovorin is actively and passively transported across cell membranes. In vivo, levoleucovorin is converted to 5-methyltetrahydrofolic acid (5-methyl-THF), the primary circulating form of active reduced folate. Levoleucovorin and 5-methyl-THF are polyglutamated intracellularly by the enzyme folylpolyglutamate synthetase. Folylpolyglutamates are active and participate in biochemical pathways that require reduced folate. D0Q6LA DB11602 Hydroxyethyl cellulose small molecule approved 9004-62-0 806.937 C36H70O19 Hydroxyethyl cellulose acts as a demulcent by relieving inflammation or irritation and dryness of eyes. It acts as one of the key ingredient and viscosity-enhancing agent to prolong corneal contact time and increase intraocular drug levels 4. DB11609 Normethadone small molecule approved 467-85-6 295.426 C20H25NO Normethadone is an opioid which suppresses coughing by central and peripheral mechanisms Label 1. DB11610 Oxilofrine small molecule approved 365-26-4 181.235 C10H15NO2 Oxilofrine is a sympathomimetic which increases adrenergic activity 1. D07QLG DB11611 Lifitegrast small molecule approved 1025967-78-5 615.48 C29H24Cl2N2O7S P20701#Integrin alpha-L Lifitegrast addresses both the symptoms and the resulting ocular surface damage by interfering with ocular inflammatory cycle 2. Lifitegrast is a lymphocyte function–associated antigen-1 antagonist through direct competitive antagonism and sequentially inhibits the T-cell recruitment, activation, and proinflammatory cytokine release associated with dry eye syndrome 4. DB11613 Velpatasvir small molecule approved 1377049-84-7 883.019 C49H54N8O8 Q5L478#Nonstructural protein 5A Velpatasvir is a small molecule direct-acting antiviral used in the treatment of hepatitis C in combination with sofosbuvir. Velpatasvir prevents viral replication by inhibiting non-structural protein 5A (NS5A) 4. DB11614 Rupatadine small molecule approved 158876-82-5 415.97 C26H26ClN3 P25105#Platelet-activating factor receptor@P70174#Histamine H1 receptor Rupatadine is an anti allergenic and acts to reduce allergic symptoms like urticaria, rhinorrhea, sneezing and itching Label. DB11619 Gestrinone small molecule approved 16320-04-0 308.4141 C21H24O2 P04278#Sex hormone-binding globulin@P06401#Progesterone receptor@P04150#Glucocorticoid receptor@P10275#Androgen receptor@P30968#Gonadotropin-releasing hormone receptor Gestrinone is a synthetic steroidal hormone which has androgenic, anti-estrogenic and anti-progestogenic properties 10. The findings of several studies suggest that gestrinone is as effective as danazol in the treatment of infertility associated with endometriosis and is better tolerated, in terms of adverse effects 1,2. D0M5RF DB11622 Dehydrocholic acid small molecule approved 81-23-2 402.531 C24H34O5 Following infusion of dehydrocholic acid (DHCA) in rats, the secretions of all the endogenous biliary bile acids were decreased within 30-60 minutes of infusion 2,4. Phospholipid secretion as well as cholesterol levels were also declined. The bile flow was increased after administration of dehydrocholic acid 1. D02ARR DB11629 Laropiprant small molecule approved 571170-77-9 435.89 C21H19ClFNO4S Not Available DB11630 Temoporfin small molecule approved 122341-38-2 680.764 C44H32N4O4 Temoporfin is a photosensitizing agent Label. It enters cancer cells and is activated via light to produce reactive species which destroy the cell. D0P5DG DB11632 Opicapone small molecule approved 923287-50-7 413.17 C15H10Cl2N4O6 P21964#Catechol O-methyltransferase Opicapone is a COMT inhibitor that serves to improve the availability and duration of action of levodopa (L-Dopa), a standard pharmacological treatment for Parkinson's Disease. Opicapone works by blocking the peripheral degradation of L-Dopa mediated by COMT.1 Opicapone has a long duration of action: following administration of a 50 mg dose, COMT inhibition lasted for more than 24 hours.10 In clinical trials, opicapone as adjunct therapy to L-Dopa plus a dopa decarboxylase inhibitor significantly improved motor fluctuations than placebo, and the effects were comparable to entacapone.1 D01SGK DB11633 Isavuconazole small molecule approved 241479-67-4 437.47 C22H17F2N5OS Q16850#Lanosterol 14-alpha demethylase@Q12809#Potassium voltage-gated channel subfamily H member 2@Q13936#Voltage-dependent L-type calcium channel subunit alpha-1C@P48051#G protein-activated inward rectifier potassium channel 2@Q92806#G protein-activated inward rectifier potassium channel 3@Q14654#ATP-sensitive inward rectifier potassium channel 11@P22460#Potassium voltage-gated channel subfamily A member 5@Q9UK17#Potassium voltage-gated channel subfamily D member 3@P51787#Potassium voltage-gated channel subfamily KQT member 1@Q14524#Sodium channel protein type 5 subunit alpha Isavucoanzole exhibits antifungal activity against most strains of Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucorales such as Rhizopus oryzae and Mucormycetes species in vivo and in vitro Label. In a cardiac electrophysiology study involving healthy subjects, isavuconazole induced dose-related shortening of the QTc interval but the additive effect of isavuconazole with other QTc-prolonging drug is unknown Label. D07VHS DB11636 Nomegestrol small molecule approved 58691-88-6 328.452 C21H28O3 Not Available DB11637 Delamanid small molecule approved 681492-22-8 534.492 C25H25F3N4O6 The minimum inhibitory concentrations (MIC) of delamanid against Mycobacterium tuberculosis isolates ranges from 0.006 to 0.024 g/mL 2. Among non-tuberculosis mycobacteria, delamanid has in vitro activity against M. kansasii and M. bovis 2. Delamanid has no in vitro activity against Gram negative or positive bacterial species and does not display cross-resistance to other anti-tuberculosis drugs 6. In murine models of chronic tuberculosis, the reduction of M. tuberculosis colony counts by delamanid was demonstrated in a dose-dependent manner 2. Repeated dosing of delamanid may cause QTc-prolongation via inhibition of cardiac potassium channel (hERG channel), and this effect is mostly contributed by the main metabolite of delamanid, DM-6705 6,2. Animal studies indicate that delamanid may attenuate vitamin K-dependent blood clotting, increase prothrombin time (PT), and activated partial thromboplastin time (APTT) 2. D0S3NU DB11640 Amifampridine small molecule approved 54-96-6 109.132 C5H7N3 Q09470#Potassium voltage-gated channel subfamily A member 1 Administration of amifampridine to patients with LES in clinical trials resulted in improvement of the compound muscle action potential (CMAP), muscle function, and quantitative myasthenia gravis (QMG) score 1. One case of a slight prolongation of the QTc interval in male patient with LEMS and euthyroid Hashimoto’s disease treated with 90 mg of amifampridine in combination with 100 mg azathioprine was reported 1. In vitro, amifampridine was shown to modulate cardiac conduction and induce phasic contractions in different arteries from several species 1. In addition, it stimulated potassium-evoked dopamine and noradrenaline release in rat hippocampal slices and upregulate acetylcholine release in the brain 1. It may also potentiate adrenergic and cholinergic neuromuscular transmission in the gatrointestinal tract 1. In a single pharmacokinetic study, no effect was observed of amifampridine phosphate on cardiac repolarization as assessed using the QTc interval 10. There were no changes in heart rate, atrioventricular conduction or cardiac depolarization as measured by the heart rate, PR and QRS interval durations 10. D0HE0Y DB11641 Vinflunine small molecule approved 162652-95-1 816.944 C45H54F2N4O8 Q7KQL5#Tubulin beta chain The antitumour effects of vinflunine are dependent on concentration and exposure duration of the drug 1. Vinflunine mediates an anti-mitotic action by inhibiting the microtubule assembly at micromolar concentrations and reducing the rate and extent of microtubule growing events 1. In vivo, vinflunine displays a significant antitumor activity against a broad spectrum of human xenografts in mice both in terms of survival prolongation and tumour growth inhibition 6. Compared with other vinca alkaloids, vinflunine is a less-potent inductor of drug resistance in vitro 3. D0OT9S DB11642 Pitolisant small molecule approved 362665-56-3 295.85 C17H26ClNO Q9Y5N1#Histamine H3 receptor@Q12809#Potassium voltage-gated channel subfamily H member 2 Pitolisant promotes wakefulness in narcolepsy by enhancing histaminergic signalling in the central nervous system. It does not significantly bind to H1, H2, or H4 receptors.10 In patients with narcolepsy in presence or absence of cataplexy, treatment of pitolisant was associated with an improvement in the level and duration of wakefulness and daytime alertness assessed by objective measures of ability to sustain wakefulness (e.g. Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS) Scores) and attention (e.g. Sustained Attention to Response Task (SART)).8 Pitolisant also improved the frequency and severity of narcolepsy-associated cataplexy.1 Pitolisant acts as a blocker at hERG channels. In two QT studies, supra-therapeutic doses of pitolisant (3-6-times the therapeutic dose, that is 108 mg to 216 mg) produced mild to moderate prolongation of QTc interval (10-13 ms).8 D01UUD DB11644 Tafamidis small molecule approved 594839-88-0 308.116 C14H7Cl2NO3 P02766#Transthyretin Tafamidis stabilizes transthyretin tetramers, reducing the amount of monomers available for amyloidogenesis.7 It has a long duration of action as it is given once daily, and a wide therapeutic window.7 DB11652 Tucatinib small molecule approved 937263-43-9 480.532 C26H24N8O2 P04626#Receptor tyrosine-protein kinase erbB-2@P21860#Receptor tyrosine-protein kinase erbB-3 By inhibiting tyrosine kinase, tucatinib exerts anti-tumor activity, reducing the size of HER-2 positive breast cancer tumors. In clinical trials, the regimen of tucatinib and trastuzumab showed enhanced activity both in vitro and in vivo when compared to either drug administered by itself.7 D09GRX DB11653 Bremelanotide small molecule approved 189691-06-3 1025.182 C50H68N14O10 Q01726#Melanocyte-stimulating hormone receptor@P32245#Melanocortin receptor 4@P41968#Melanocortin receptor 3@P33032#Melanocortin receptor 5@Q01718#Adrenocorticotropic hormone receptor Bremelanotide is a melanocortin receptor agonist injected 45 minutes before anticipated sexual activity.5 Agonism of the melanocortin receptor MC1R also leads to increased melanin expression.5 Patients taking bremelanotide may also experience nausea, headache, and vomiting.5 D0X9PF DB11660 Latanoprostene bunod small molecule approved 860005-21-6 507.624 C27H41NO8 P43088#Prostaglandin F2-alpha receptor Upon applying an appropriate dose of latanoprost bunod, reduction in intraocular pressure begins approximately 1 to 3 hours later with a maximum intraocular pressure reduction effect demonstrated after 11 to 13 hours Label. DB11672 Curcumin small molecule approved 458-37-7 368.3799 C21H20O6 P37231#Peroxisome proliferator-activated receptor gamma@P11473#Vitamin D3 receptor@O15440#Multidrug resistance-associated protein 5@P16152#Carbonyl reductase [NADPH] 1@P09211#Glutathione S-transferase P Intravenous application of 25 mg/kg bw curcumin to rats resulted in an increase in bile flow by 80 and 120% 3. In the rat model of inflammation, curcumin was shown to inhibit edema formation. In nude mouse that had been injected subcutaneously with prostate cancer cells, administration of curcumin caused a marked decrease in the extent of cell proliferation, a significant increase of apoptosis and micro-vessel density 3. Curcumin may exert choleretic effects by increasing biliary excretion of bile salts, cholesterol, and bilirubin, as well as increasing bile solubility 3. Curcumin inhibited arachidonic acid-induced platelet aggregation in vitro 3. D07SDQ DB11677 Triheptanoin small molecule approved 620-67-7 428.61 C24H44O6 Triheptanoin is a source of medium chain fatty acids for patients with lc-FAODs.4 It has a moderate duration of action and a wide therapeutic window.4 Patients should be counselled regarding the risk of feeding tube dysfunction and intestinal malabsorption due to pancreatic insufficiency.4 D00MLW DB11689 Selumetinib small molecule approved 606143-52-6 457.68 C17H15BrClFN4O3 Q02750#Dual specificity mitogen-activated protein kinase kinase 1@P36507#Dual specificity mitogen-activated protein kinase kinase 2 Selumetinib is a non-ATP-competitive mitogen-activated protein kinase kinase 1 and 2 (MEK1 and MEK2) inhibitor.6 By selectively targeting MEK1 and MEK2, selumetinib is able to inhibit oncogenic downstream effects of the Raf-MEK-ERK signaling pathway, which is often overactive in certain types of cancer.6 Indeed, a study investigating the effects of selumetinib in children with NF-1 found that treatment with the anti-neoplastic resulted in reduced tumor size.3 Decreases in tumor-associated pain and improvements in overall function were also subjectively reported.3 D0T5DP DB11691 Naldemedine small molecule approved 916072-89-4 570.646 C32H34N4O6 P35372#Mu-type opioid receptor@P41143#Delta-type opioid receptor@P41145#Kappa-type opioid receptor Naldemedine is an opioid receptor antagonist with restricted movement across the blood brain barrier Label. This allows it to antagonize the periperal effects of opioid drugs such as constipation without interfering with the effects on the central nervous system. DB11699 Tropisetron small molecule approved 89565-68-4 284.3529 C17H20N2O2 P46098#5-hydroxytryptamine receptor 3A Not Available D0K0KH DB11703 Acalabrutinib small molecule approved 1420477-60-6 465.517 C26H23N7O2 Q06187#Tyrosine-protein kinase BTK Acalabrutinib is a Bruton Tyrosine Kinase inhibitor that prevents the proliferation, trafficking, chemotaxis, and adhesion of B cells.6 It is taken every 12 hours and can cause other effects such as atrial fibrillation, other malignancies, cytopenia, hemorrhage, and infection.6 D09PQZ DB11705 Iomeprol small molecule approved 78649-41-9 777.089 C17H22I3N3O8 Not Available D09RUW DB11712 Tezacaftor small molecule approved 1152311-62-0 520.505 C26H27F3N2O6 P13569#Cystic fibrosis transmembrane conductance regulator Clinical studies have shown a significant decrease in sweat chloride and an increase in the forced expiratory volume (FEV), a measure of lung function, following Tevacaftor/Ivacaftor therapy.1 Phase 3 clinical studies have shown that a significant increase in forced expiratory volume was attained at 4 and 8 weeks after initiating this drug. The above effects lead to improvement of the respiratory symptoms of cystic fibrosis. Tezacaftor does not induce clinically significant QT prolongation.2 When given with ivacaftor, tezacaftor can lead to liver transaminase elevations.14 Testing of transaminases (ALT and AST) levels should occur before starting this combination every 3 months during the first year of treatment, and every year afterwards. Patients with a history of transaminase elevations should be monitored more frequently.14 DB11718 Encorafenib small molecule approved 1269440-17-6 540.01 C22H27ClFN7O4S P15056#Serine/threonine-protein kinase B-raf@P24385#G1/S-specific cyclin-D1 Encorafenib has shown improved efficacy in the treatment of metastatic melanoma 3. DB11730 Ribociclib small molecule approved 1211441-98-3 434.548 C23H30N8O P11802#Cyclin-dependent kinase 4@Q00534#Cyclin-dependent kinase 6 Not Available DB11732 Lasmiditan small molecule approved 439239-90-4 377.367 C19H18F3N3O2 P30939#5-hydroxytryptamine receptor 1F Lasmiditan belongs to a new and novel class of acute anti-migraine medications that exert their effects via inhibition of neuronal firing rather than vasoconstriction of cerebral arteries.2 Lasmiditan appears to have a relatively quick onset of action (an important characteristic in acute migraine treatment) with some patients reporting benefit within 20 minutes.6 Due to its ability to cause CNS depression (e.g. drowsiness, dizziness), lasmiditan may cause significant driving impairment and patients should be advised not to participate in activities requiring mental alertness for at least 8 hours after dosing.7 Lasmiditan may carry some potential for abuse and should be used with caution in patients who may be at risk of drug abuse - its controlled substance scheduling is currently under review in the United States by the Drug Enforcement Administration (DEA).7 D01NQM DB11735 Galactose small molecule approved 59-23-4 180.1559 C6H12O6 Galactose is a naturally occurring monosaccharide that forms the disaccharide lactose when combined with glucose (another monosaccharide) 6. Subsequently, when lactose or small amounts of free galactose found in various common dairy products (and other foods) are consumed, the hydrolysis of lactose to glucose and galactose occurs and galactose is itself further metabolized to generate glucose 6. Such glucose is, of course, ultimately relied upon and used as the primary metabolic fuel for humans in a variety of biological reactions. DB11738 Rilmenidine small molecule approved 54187-04-1 180.251 C10H16N2O P08913#Alpha-2A adrenergic receptor Not Available D06OFS DB11742 Ebastine small molecule approved 90729-43-4 469.6576 C32H39NO2 Not Available DB11748 Benfotiamine small molecule approved 22457-89-2 466.45 C19H23N4O6PS Not Available DB11750 Clobetasol small molecule approved 25122-41-2 410.907 C22H28ClFO4 Not Available D0FL5V DB11753 Rifamycin small molecule approved 6998-60-3 697.778 C37H47NO12 P0A8V2#DNA-directed RNA polymerase subunit beta@P0A7Z4#DNA-directed RNA polymerase subunit alpha@P0A8T7#DNA-directed RNA polymerase subunit beta' Rifamycin is known to be effective against Gram-positive and Gram-negative pathogens and mycobacteria. It is very effective against E. coli reporting a MIC90 of 64-128 mcg/ml without showing cross-resistance with other antimicrobial agents.4 D0FX2Q DB11757 Istradefylline small molecule approved 155270-99-8 384.436 C20H24N4O4 P29274#Adenosine receptor A2a@P30542#Adenosine receptor A1 Istradefylline is a selective adenosine A2A receptor inhibitor.1,2 It has a long duration of action as it is given once daily and has a half life of 64-69 hours.1,2,8 Patients taking this medication should be monitored for dyskinesia, hallucinations, and lack of impulse control.8 Consider dose reductions for these patients.8 D0F4ZY DB11760 Talazoparib small molecule approved 1207456-01-6 380.359 C19H14F2N6O P09874#Poly [ADP-ribose] polymerase 1@Q9UGN5#Poly [ADP-ribose] polymerase 2 Talazoparib prevents PARP-mediated repair of DNA damage in cancer cells, allowing accumulation of damage and PARP-DNA complexes Label. Repair related errors by error prone secondary repair pathways may also contribute to the cytotoxicity of talazoparib 2. D0GV8J DB11761 Tenapanor small molecule approved 1234423-95-0 1145.04 C50H66Cl4N8O10S2 P48764#Sodium/hydrogen exchanger 3 Through the inhibition of dietary sodium absorption tenapanor causes an increase in water secretion into the intestines, thereby decreasing transit time and softening stool consistency.6 D04TQO DB11768 Zytron small molecule approved 299-85-4 314.16 C10H14Cl2NO2PS Not Available DB11791 Capmatinib small molecule approved 1029712-80-8 412.428 C23H17FN6O P08581#Hepatocyte growth factor receptor Capmatinib inhibits the overactivity of c-Met, a receptor tyrosine kinase encoded by the MET proto-oncogene.3 Mutations in MET are involved in the proliferation of many cancers, including non-small cell lung cancer (NSCLC).3,2 D07OJZ DB11793 Niraparib small molecule approved 1038915-60-4 320.396 C19H20N4O P09874#Poly [ADP-ribose] polymerase 1@Q9UGN5#Poly [ADP-ribose] polymerase 2 Cardiovascular Effects: DB11799 Bictegravir small molecule approved 1611493-60-7 449.386 C21H18F3N3O5 Q72547#Reverse transcriptase/RNaseH@Q7ZJM1#Integrase Bictegravir is an HIV-1 integrase strand transfer inhibitor (INSTI). Bictegravir (BIC) inhibits HIV-1 virus replication into the human genome. It can be taken once daily without additional dosing 2,3,4,5. Bictegravir (BIC) inhibits strand transfer of viral DNA into the host genome and thereby prevents HIV-1 replication 5. DB11815 Tilarginine small molecule approved 17035-90-4 188.2275 C7H16N4O2 Not Available DB11817 Baricitinib small molecule approved 1187594-09-7 371.42 C16H17N7O2S P23458#Tyrosine-protein kinase JAK1@O60674#Tyrosine-protein kinase JAK2@P52333#Tyrosine-protein kinase JAK3@P29597#Non-receptor tyrosine-protein kinase TYK2 Baricitinib is a disease-modifying antirheumatic drug (DMARD) used to ameliorate symptoms and slow down the progression of rheumatoid arthritis. In animal models of inflammatory arthritis, baricitinib was shown to have significant anti-inflammatory effects but also led to the preservation of cartilage and bone, with no detectable suppression of humoral immunity or adverse hematologic effects.1 Baricitinib decreased the levels of immunoglobulins and serum C-reactive protein in patients with rheumatoid arthritis.9 D0Y7IC DB11823 Esketamine small molecule approved 33643-46-8 237.73 C13H16ClNO Q13224#Glutamate receptor ionotropic, NMDA 2B@P23560#Brain-derived neurotrophic factor@Q16620#BDNF/NT-3 growth factors receptor@P13639#Elongation factor 2@Q05586#Glutamate receptor ionotropic, NMDA 1@Q12879#Glutamate receptor ionotropic, NMDA 2A@Q13224#Glutamate receptor ionotropic, NMDA 2B General effects D0TP5H DB11827 Ertugliflozin small molecule approved 1210344-57-2 436.89 C22H25ClO7 P31639#Sodium/glucose cotransporter 2 Administration of ertugliflozin increases urinary glucose excretion which leads to a negative balance and osmotic diuresis. Thus, this antidiabetic agent has been reported to significantly reduce the body weight and blood pressure of diabetic patients.4 DB11828 Neratinib small molecule approved 698387-09-6 557.05 C30H29ClN6O3 P00533#Epidermal growth factor receptor Neratinib is a tyrosine kinase inhibitor which exhibits antitumor action against Epidermal Growth Factor Receptor (EGFR), HER2, and Human Epidermal Growth Factor Receptor 4 (HER4) postive carcinomas [FDA Label]. DB11835 Indium In-111 pentetreotide small molecule approved 139096-04-1 1472.41 C62H80InN12O19S2 Not Available DB11837 Osilodrostat small molecule approved 928134-65-0 227.242 C13H10FN3 P15538#Cytochrome P450 11B1, mitochondrial@P19099#Cytochrome P450 11B2, mitochondrial Osilodrostat lowers endogenous cortisol levels by inhibiting the enzyme that catalyzes the final step in cortisol synthesis.6 As endogenous cortisol levels function as a surrogate marker for drug effect, 24-hour urine free cortisol levels should be assessed 1-2x weekly during the initial titration stage and every 1-2 months thereafter to ensure cortisol levels remain physiologically appropriate.6 Osilodrostat is highly metabolized and requires dose adjustments in patient with hepatic dysfunction.6 D03AJU DB11842 Angiotensin II small molecule approved 4474-91-3 1046.1786 C50H71N13O12 P30556#Type-1 angiotensin II receptor Angiotensin II is a naturally occurring peptide hormone of the renin-angiotensin-aldosterone-system (RAAS) that has the capacity to cause vasoconstriction and an increase in blood pressure in the human body. Label DB11855 Revefenacin small molecule approved 864750-70-9 597.76 C35H43N5O4 P08172#Muscarinic acetylcholine receptor M2@P20309#Muscarinic acetylcholine receptor M3 Revefenacin has been reported to produce a sustained, long-acting bronchodilation with lower anti-muscarinic-related side effects. In clinical trials, revefenacin demonstrated to be of a long duration of action and low systemic exposure in patients with COPD. Also, it was reported that a dose of 88 mcg can produce a clinically effective bronchodilation measured by through forced expiratory volume in 1s and serial spirometric assessments.3 D0K1ST DB11859 Brexanolone small molecule approved 516-54-1 318.4935 C21H34O2 P28472#Gamma-aminobutyric acid receptor subunit beta-3 Brexanolone potentiated GABA-mediated currents from recombinant human GABA(a) receptors in mammalian cells expressing α1β2γ2 receptor subunits, α4β3δ receptor subunits, and α6β3δ receptor subunits Label7,9. DB11901 Apalutamide small molecule approved 956104-40-8 477.44 C21H15F4N5O2S P10275#Androgen receptor@P28472#Gamma-aminobutyric acid receptor subunit beta-3 In an open-label, uncontrolled, multi-center, single-arm dedicated QT study in 45 patients with CRPC, an exposure-QT analysis suggested a concentration-dependent increase in QTcF for apalutamide and its active metabolite. Apalutamide demonstrated an antitumor activity in the mouse xenograft models of prostate cancer, where it decreased tumor cell proliferation and reduced tumor volume Label. DB11915 Valbenazine small molecule approved 1025504-45-3 418.578 C24H38N2O4 Valbenazine decreases the availability of monoamine neurotransmitters by preventing their storage in synaptic vesicles 2. This is believed to be the reason behind its therapeutic effect in tardive dyskinesia although the exact mechanism is unknown. DB11921 Deflazacort small molecule approved 14484-47-0 441.524 C25H31NO6 P04150#Glucocorticoid receptor Deflazacort exerts anti-inflammatory activity in DMD, likely improving various symptoms, including muscle weakness and cardiorespiratory symptoms in addition to delaying their onset.6 This allows for an increased quality of life and prevents the necessity for surgical procedures, such as those for scoliosis, which is associated with DMD. Studies showed significant preservation of muscle mass in patients generally treated with 0.9 mg/kg/day of deflazacort compared to a control group. The following findings are based on clinical studies using deflazacort on a long term basis6,8: D09WYX DB11936 Bempedoic acid small molecule approved 738606-46-7 344.492 C19H36O5 P53396#ATP-citrate synthase Bempedoic acid inhibits the synthesis of cholesterol in the liver, reducing LDL-C levels. This reduces the development of atherosclerotic plaques that may increase the risk of cardiovascular events.1,4 Earlier clinical trials studying the effects of bempedoic acid showed a dose‐dependent reduction of LDL‐C levels in addition to decreased LDL particle number, and reduced levels of apolipoprotein B, non–HDL cholesterol, and high‐sensitivity C‐reactive protein.2 D0D9NY DB11942 Selinexor small molecule approved 1393477-72-9 443.313 C17H11F6N7O O14980#Exportin-1 Selinexor causes cell cycle arrest and apoptosis in cancer cells.11 D00LNW DB11943 Delafloxacin small molecule approved 189279-58-1 440.76 C18H12ClF3N4O4 P0AFI2#DNA topoisomerase 4 subunit A@P0AES4#DNA gyrase subunit A Delafloxacin is a fluoroquinolone antibacterial drug which kills bacterial cells Label. DB11951 Lemborexant small molecule approved 1369764-02-2 410.425 C22H20F2N4O2 O43613#Orexin receptor type 1@O43614#Orexin receptor type 2 Lemborexant promotes sleep by antagonizing the actions of wake-promoting chemicals in the brain.5 Episodes of complex sleep behaviors (e.g. eating food, having sex, making phone calls) have been reported in patients using lemborexant - these events may occur in hypnotic-naive and hyponotic-experienced patients, and patients are unlikely to remember these events. Patients exhibiting complex sleep behaviors should discontinue lemborexant immediately. Lemborexant may carry some risk of abuse, and should be used with caution in patients with a history of alcohol or drug addiction. Its controlled substance schedule is currently under review by the Drug Enforcement Administration.5 D0A7ZK DB11952 Duvelisib small molecule approved 1201438-56-3 416.87 C22H17ClN6O P48736#Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform@O00329#Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Preclinical data showed that duvelisib presents cytotoxic actions at micromolar doses and antagonizes the activation of downstream signaling even in the presence of the mutation BTK C481S, which allows for the treatment of patients resistant to ibrutinib.4 DB11963 Dacomitinib small molecule approved 1110813-31-4 469.939 C24H25ClFN5O2 P00533#Epidermal growth factor receptor Preclinical data suggested that dacomitinib increases the inhibition of the epidermal growth factor receptor kinase domain as well as the activity in cell lines harboring resistance mutations such as T790M. This activity further produced a significant reduction of EGFR phosphorylation and cell viability. In these studies, non-small cell lymphoma cancer cell lines with L858R/T790M mutations where used and an IC50 of about 280 nmol/L was observed.3 D06XXH DB11967 Binimetinib small molecule approved 606143-89-9 441.233 C17H15BrF2N4O3 Q13233#Mitogen-activated protein kinase kinase kinase 1@P36507#Dual specificity mitogen-activated protein kinase kinase 2@P05231#Interleukin-6@P01375#Tumor necrosis factor@P01584#Interleukin-1 beta Binimetinib is a MEK inhibitor. MEK is an enzyme that regulates the biosynthesis of the inflammatory cytokines TNF, IL-6 and IL-1. MEK inhibitors interfere with these biosynthetic processes 7. It is a chemotherapeutic agent that has anti-tumor activity 10, 1. DB11978 Glasdegib small molecule approved 1095173-27-5 374.448 C21H22N6O Q99835#Smoothened homolog In preclinical studies, glasdegib achieved a significant reduction in leukemic stem cell burden in xenograft models and a reduction in cell population expressing leukemic stem cell markers.2 DB11979 Elagolix small molecule approved 834153-87-6 631.6 C32H30F5N3O5 P30968#Gonadotropin-releasing hormone receptor During a three menstrual cycle study in healthy women, an elagolix 150 mg once daily regimen and a 200 mg twice daily regimen resulted in an ovulation rate of about 50% and 32%, respectively Label. In Phase 3 trials in women with endometriosis, elagolix caused a dose-dependent reduction in median estradiol concentrations to approximately 42 pg/mL for the 150 mg once daily regimen and 12 pg/mL for the 200 mg twice daily regimen Label. D0UI3T DB11986 Entrectinib small molecule approved 1108743-60-7 560.65 C31H34F2N6O2 P04629#High affinity nerve growth factor receptor@Q16288#NT-3 growth factor receptor@P08922#Proto-oncogene tyrosine-protein kinase ROS@Q16620#BDNF/NT-3 growth factors receptor@O60674#Tyrosine-protein kinase JAK2@Q07912#Activated CDC42 kinase 1 Entrectinib and its active metabolite suppress several pathways which contribute to cell survival and proliferation.2,4,5,6,7 This suppression shifts the balance in favor of apoptosis thereby preventing cancer cell growth and shrinking tumors. D0O0LS DB11989 Benznidazole small molecule approved 22994-85-0 260.253 C12H12N4O3 Benznidazole is a trypanocidal agent which kills the causative organism in Chagas disease, Trypanosoma cruzi 1. D04XGT DB11994 Diacerein small molecule approved 13739-02-1 368.297 C19H12O8 P09917#Arachidonate 5-lipoxygenase@P55055#Oxysterols receptor LXR-beta@P10635#Cytochrome P450 2D6@P05177#Cytochrome P450 1A2@P11712#Cytochrome P450 2C9@P05181#Cytochrome P450 2E1@Q13133#Oxysterols receptor LXR-alpha@P08684#Cytochrome P450 3A4 Decreases inflammation and cartilage destruction and also corrects altered osteoblast acitivity 3 4 5. D0N1FS DB11995 Avatrombopag small molecule approved 570406-98-3 649.65 C29H34Cl2N6O3S2 P40238#Thrombopoietin receptor@Q9UNQ0#ATP-binding cassette sub-family G member 2@Q8TCC7#Solute carrier family 22 member 8 In a study of efficacy, avatrombopag resulted in dose and exposure-dependent elevations in platelet counts in adults 1. The onset of the platelet count increase was noted within 3 to 5 days of the start of a 5-day treatment course, with the highest level of effect measured after 10 to 13 days. Following this, platelet counts decreased gradually, returning to near baseline values at the 35-day point Label.