Details of the Drug Therapeutic Target (DTT)
General Information of Drug Therapeutic Target (DTT) (ID: TTCM4B3)
DTT Name | Nitric-oxide synthase endothelial (NOS3) | ||||
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Synonyms | Nitric oxide synthase, endothelial; NOSIII; NOS,type III; NOS type III; Endothelial nitric oxide synthase; Endothelial NOS; ENOS; EC-NOS; Constitutive NOS; CNOS | ||||
Gene Name | NOS3 | ||||
DTT Type |
Clinical trial target
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BioChemical Class |
Paired donor oxygen oxidoreductase
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UniProt ID | |||||
TTD ID | |||||
3D Structure | |||||
EC Number |
EC 1.14.13.39
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Sequence |
MGNLKSVAQEPGPPCGLGLGLGLGLCGKQGPATPAPEPSRAPASLLPPAPEHSPPSSPLT
QPPEGPKFPRVKNWEVGSITYDTLSAQAQQDGPCTPRRCLGSLVFPRKLQGRPSPGPPAP EQLLSQARDFINQYYSSIKRSGSQAHEQRLQEVEAEVAATGTYQLRESELVFGAKQAWRN APRCVGRIQWGKLQVFDARDCRSAQEMFTYICNHIKYATNRGNLRSAITVFPQRCPGRGD FRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDDPP ELFLLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMST EIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINVAVLHSYQLAKVTIVDH HAATASFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYFLSPAFRYQPDPW KGSAAKGTGITRKKTFKEVANAVKISASLMGTVMAKRVKATILYGSETGRAQSYAQQLGR LFRKAFDPRVLCMDEYDVVSLEHETLVLVVTSTFGNGDPPENGESFAAALMEMSGPYNSS PRPEQHKSYKIRFNSISCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYPHF CAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAQAAFQAACETFCVGEDAKAAA RDIFSPKRSWKRQRYRLSAQAEGLQLLPGLIHVHRRKMFQATIRSVENLQSSKSTRATIL VRLDTGGQEGLQYQPGDHIGVCPPNRPGLVEALLSRVEDPPAPTEPVAVEQLEKGSPGGP PPGWVRDPRLPPCTLRQALTFFLDITSPPSPQLLRLLSTLAEEPREQQELEALSQDPRRY EEWKWFRCPTLLEVLEQFPSVALPAPLLLTQLPLLQPRYYSVSSAPSTHPGEIHLTVAVL AYRTQDGLGPLHYGVCSTWLSQLKPGDPVPCFIRGAPSFRLPPDPSLPCILVGPGTGIAP FRGFWQERLHDIESKGLQPTPMTLVFGCRCSQLDHLYRDEVQNAQQRGVFGRVLTAFSRE PDNPKTYVQDILRTELAAEVHRVLCLERGHMFVCGDVTMATNVLQTVQRILATEGDMELD EAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERQLRGAVPWAFDPPGSDT NSP |
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Function |
NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway.
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KEGG Pathway |
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Reactome Pathway | |||||
BioCyc Pathway | |||||
Molecular Interaction Atlas (MIA) of This DTT
Molecular Interaction Atlas (MIA) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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6 Clinical Trial Drug(s) Targeting This DTT
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1 Discontinued Drug(s) Targeting This DTT
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81 Investigative Drug(s) Targeting This DTT
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Molecular Expression Atlas (MEA) of This DTT
The Drug-Metabolizing Enzyme (DME) Role of This DTT
DTT DME Name | Nitric oxide synthase endothelial (NOS3) | |||||||||||||||||||||||||||
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Gene Name | NOS3 | |||||||||||||||||||||||||||
1 Approved Drug(s) Metabolized by This DTT
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References
1 | Effect of tilarginine acetate in patients with acute myocardial infarction and cardiogenic shock: the TRIUMPH randomized controlled trial. JAMA. 2007 Apr 18;297(15):1657-66. | ||||
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2 | CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008. | ||||
3 | Counter-regulation by atorvastatin of gene modulations induced by L-NAME hypertension is associated with vascular protection. Vascul Pharmacol. 2009 Oct;51(4):253-61. | ||||
4 | Nitric oxide synthase inhibitor (MTR-105) during open-heart surgery. A pilot double-blind placebo-controlled study of hemodynamic effects and safety. Cardiology. 2008;111(3):181-7. | ||||
5 | Nitric oxide synthase inhibition with the antipterin VAS203 improves outcome in moderate and severe traumatic brain injury: a placebo-controlled randomized Phase IIa trial (NOSTRA). J Neurotrauma. 2014 Oct 1;31(19):1599-606. | ||||
6 | Feasibility of using autologous transplantation to evaluate hematopoietic stem cell-based gene therapy strategies in transgenic mouse models of human disease. Mol Ther. 2002 Sep;6(3):422-8. | ||||
7 | Discovery of a series of aminopiperidines as novel iNOS inhibitors. Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43. | ||||
8 | Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases. Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11. | ||||
9 | Bicyclic amidine inhibitors of nitric oxide synthase: discovery of perhydro-iminopyrindine and perhydro-iminoquinoline as potent, orally active inh... Bioorg Med Chem Lett. 2005 Apr 15;15(8):1997-2001. | ||||
10 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | ||||
11 | 2-Iminopiperidine and other 2-iminoazaheterocycles as potent inhibitors of human nitric oxide synthase isoforms. J Med Chem. 1996 Feb 2;39(3):669-72. | ||||
12 | Novel 2-aminobenzothiazoles as selective neuronal nitric oxide synthase inhibitors. Bioorg Med Chem Lett. 2007 May 1;17(9):2540-4. | ||||
13 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | ||||
14 | Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase. Nat Chem Biol. 2008 Nov;4(11):700-7. | ||||
15 | Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase. Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44. | ||||
16 | Inhibitory effects of a series of 7-substituted-indazoles toward nitric oxide synthases: particular potency of 1H-indazole-7-carbonitrile. Bioorg Med Chem. 2008 Jun 1;16(11):5962-73. | ||||
17 | Design and synthesis of orally bioavailable inhibitors of inducible nitric oxide synthase. Part 1: synthesis and biological evaluation of dihydropy... Bioorg Med Chem Lett. 2002 Sep 2;12(17):2291-4. | ||||
18 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | ||||
19 | Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fl... J Med Chem. 2009 Apr 23;52(8):2443-53. | ||||
20 | Selective heterocyclic amidine inhibitors of human inducible nitric oxide synthase. Bioorg Med Chem Lett. 2001 Oct 8;11(19):2651-3. | ||||
21 | Endothelial nitric oxide synthase: the Cinderella of inflammation Trends Pharmacol Sci. 2003 Feb;24(2):91-5. | ||||
22 | Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease. Clin Chem Lab Med. 2007;45(12):1683-7. | ||||
23 | Structure-activity relationship of novel and known inhibitors of human dimethylarginine dimethylaminohydrolase-1: alkenyl-amidines as new leads. Bioorg Med Chem. 2008 Dec 15;16(24):10205-9. | ||||
24 | Crystal structure of nitric oxide synthase bound to nitro indazole reveals a novel inactivation mechanism. Biochemistry. 2001 Nov 13;40(45):13448-55. | ||||
25 | Evaluation of 3-substituted arginine analogs as selective inhibitors of human nitric oxide synthase isozymes. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2881-5. | ||||
26 | The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75. | ||||