Therapeutic Targets Database
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TTD Target ID: TTDS00337

Target Information
NameNitric oxide synthase, inducible    
Type of targetSuccessful target    
SynonymsHEP-NOS    
Hepatocyte NOS    
INOS    
Inducible NOS    
Inducible nitric oxide synthase    
NOS, type II    
DiseaseIschemia reperfusion injuries
[ICD9: 459.89   ICD10: I99.8]
[1]
Drug(s)HydrocortisoneApprovedInflammatory diseases[2]
BioChemical ClassOxidoreductases acting on paired donors    
EC NumberEC 1.14.13.39
PathwayAlzheimer's disease
Amyotrophic lateral sclerosis (ALS)
Arginine and proline metabolism
Calcium signaling pathway
Long-term depression
Metabolic pathways
Pathways in cancer
Small cell lung cancer
UniProt IDP35228
PDB Structure1NSI; 2LL6; 2NSI; 3E7G; 3EJ8; 3HR4; 4NOS.    
FunctionProduces nitric oxide (no) which is a messenger molecule with diverse functions throughout the body. In macrophages, no mediates tumoricidal and bactericidal actions.    
SequenceMACPWKFLFKTKFHQYAMNGEKDINNNVEKAPCATSSPVTQDDLQYHNLSKQQNESPQPL VETGKKSPESLVKLDATPLSSPRHVRIKNWGSGMTFQDTLHHKAKGILTCRSKSCLGSIM TPKSLTRGPRDKPTPPDELLPQAIEFVNQYYGSFKEAKIEEHLARVEAVTKEIETTGTYQ LTGDELIFATKQAWRNAPRCIGRIQWSNLQVFDARSCSTAREMFEHICRHVRYSTNNGNI RSAITVFPQRSDGKHDFRVWNAQLIRYAGYQMPDGSIRGDPANVEFTQLCIDLGWKPKYG RFDVVPLVLQANGRDPELFEIPPDLVLEVAMEHPKYEWFRELELKWYALPAVANMLLEVG GLEFPGCPFNGWYMGTEIGVRDFCDVQRYNILEEVGRRMGLETHKLASLWKDQAVVEINI AVLHSFQKQNVTIMDHHSAAESFMKYMQNEYRSRGGCPADWIWLVPPMSGSITPVFHQEM LNYVLSPFYYYQVEAWKTHVWQDEKRRPKRREIPLKVLVKAVLFACMLMRKTMASRVRVT ILFATETGKSEALAWDLGALFSCAFNPKVVCMDKYRLSCLEEERLLLVVTSTFGNGDCPG NGEKLKKSLFMLKELNNKFRYAVFGLGSSMYPRFCAFAHDIDQKLSHLGASQLTPMGEGD ELSGQEDAFRSWAVQTFKAACETFDVRGKQHIQIPKLYTSNVTWDPHHYRLVQDSQPLDL SKALSSMHAKNVFTMRLKSRQNLQSPTSSRATILVELSCEDGQGLNYLPGEHLGVCPGNQ PALVQGILERVVDGPTPHQTVRLEALDESGSYWVSDKRLPPCSLSQALTYFLDITTPPTQ LLLQKLAQVATEEPERQRLEALCQPSEYSKWKFTNSPTFLEVLEEFPSLRVSAGFLLSQL PILKPRFYSISSSRDHTPTEIHLTVAVVTYHTRDGQGPLHHGVCSTWLNSLKPQDPVPCF VRNASGFHLPEDPSHPCILIGPGTGIAPFRSFWQQRLHDSQHKGVRGGRMTLVFGCRRPD EDHIYQEEMLEMAQKGVLHAVHTAYSRLPGKPKVYVQDILRQQLASEVLRVLHKEPGHLY VCGDVRMARDVAHTLKQLVAAKLKLNEEQVEDYFFQLKSQKRYHEDIFGAVFPYEAKKDR VAVQPSSLEMSAL
Related US Patent6,225,305
6,297,276
6,344,473
6,344,483
6,355,689
6,362,195
6,372,733
6,391,887
6,403,830
6,410,542
6,451,821
6,465,518
6,465,686
6,495,544
6,495,606
6,525,051
6,545,170
6,552,052
6,576,780
6,579,883
6,586,471
6,586,474
6,620,848
6,670,473
Target ValidationClick to Find Target Validation Information.    
Inhibitor ([3]
(4S,5R)-4,5-Diethyl-oxazolidin-[4]
(4S,5R)-4,5-Dimethyl-oxazolidin-[4]
(4S,5R)-4,5-Dipropyl-oxazolidin-[4]
(4S,5S)-4,5-Diethyl-oxazolidin-[4]
(4S,5S)-4,5-Dipropyl-oxazolidin-[4]
(5-Imino-[1,4]thiazepan-3-yl)-methanol[5]
(5S,6R)-[Octahydro-quinolin-[6]
(5S,6S)-[Octahydro-quinolin-[6]
(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin[7]
(E)-4-Methyl-6-[8]
(R)-3-Propyl-[1,4]thiazepan-[5]
(S)-2-Amino-5-[9]
(S)-2-Amino-6-[[9]
(S)-3-Propyl-[1,4]thiazepan-[5]
(S)-6-Amino-2-[5]
(S)-N-[10]
1- (6-Amino-4-methylpyridin-2-yl)propan-2-ol[8]
2- (2-Amino-ethyl)-7-imino-azepane[3]
2-Amino-5- (N-nitro-guanidino)-pentanoic acid[9]
2-Methyl-[1,4]thiazepan- (5E)-ylideneamine[5]
3,4-Dihydro-1H-quinolin- (2E)-ylideneamine[6]
3,4-Dimethyl-pyrrolidin- (2Z)-ylideneamine[11]
3- (2-Amino-ethyl)-5-imino-[1,4]oxazepane[3]
3- (2-Nitro-ethyl)-[1,4]oxazepan-[3]
3-Bromo-1H-indazole-7-carbonitrile[12]
3-Bromo-7-Nitroindazole[7]
3-Butyl-[1,4]oxazepan- (5Z)-ylideneamine[3]
3-Butyl-[1,4]thiazepan- (5E)-ylideneamine[5]
3-Ethyl-[1,4]thiazepan- (5E)-ylideneamine[5]
3-Isobutyl-[1,4]thiazepan- (5E)-ylideneamine[5]
3-Methyl-[1,4]thiazepan- (5E)-ylideneamine[5]
3-Methyl-pyrrolidin- (2Z)-ylideneamine[11]
3-Propyl-[1,4]thiazepan- (5E)-ylideneamine[5]
3-bromo-7-nitro-1H-indazole[13]
4,5,6,7-tetrafluoro-3-methyl-1H-indazole[13]
4,5,6,7-tetrafluoro-3-perfluorophenyl-1H-indazole[13]
4,5-Dimethyl-pyrrolidin- (2Z)-ylideneamine[11]
4- (1H-IMIDAZOL-1-YL)PHENOL[14]
4-Butyl-thiazolidin- (2E)-ylideneamine[11]
4-Ethyl-3-methyl-pyrrolidin- (2Z)-ylideneamine[11]
4-Ethyl-5-methyl-pyrrolidin- (2Z)-ylideneamine[11]
4-Ethyl-oxazolidin- (2Z)-ylideneamine[4]
4-Ethyl-pyrrolidin- (2Z)-ylideneamine[11]
4-Isopropyl-pyrrolidin- (2Z)-ylideneamine[11]
4-Methyl-5-propyl-pyrrolidin- (2Z)-ylideneamine[11]
4-Methyl-6- (2-methylprop-1-enyl)pyridin-2-amine[8]
4-Methyl-oxazolidin- (2Z)-ylideneamine[4]
4-Methyl-piperidin- (2E)-ylideneamine[6]
4-Methyl-pyrrolidin- (2Z)-ylideneamine[11]
4-[ (2-Methyl-1H-imidazol-1-yl)methyl]pyridine[10]
4-methyl-6-propylpyridin-2-amine[15]
4-methylpyridin-2-amine[15]
4r-Fluoro-N6-Ethanimidoyl-L-Lysine[7]
5-Bromomethyl-oxazolidin- (2Z)-ylideneamine[4]
5-Ethyl-4-methyl-pyrrolidin- (2Z)-ylideneamine[11]
5-Ethyl-4-propyl-pyrrolidin- (2Z)-ylideneamine[11]
5-Ethyl-oxazolidin- (2Z)-ylideneamine[4]
5-Methyl-4-propyl-pyrrolidin- (2Z)-ylideneamine[11]
5-Methyl-oxazolidin- (2Z)-ylideneamine[4]
5-Methyl-pyrrolidin- (2Z)-ylideneamine[11]
5-Nitroindazole[7]
6- (2-Fluoropropyl)-4-methylpyridin-2-amine[8]
6- (3-Fluoropropyl)-4-methylpyridin-2-amine[8]
6- (4-Fluorobutyl)-4-methylpyridin-2-amine[8]
6-Nitroindazole[7]
6-isobutyl-4-methylpyridin-2-amine[8]
6-methyl-5,6-dihydro-4H-1,3-thiazin-2-amine[16]
7,8-Dihydro-L-Biopterin[17]
7,8-dihydrobiopterin[7]
7- (2-Nitro-ethyl)-azepan-[3]
7-Butyl-azepan- (2Z)-ylideneamine[3]
7-Methyl-[1,4]thiazepan- (5E)-ylideneamine[5]
7-Nitroindazole[7]
7-nitro-1H-indazole[13]
AMINOTHIAZOLINE[18]
AR-C102222[15]
AR-C133057XX[15]
Aminoguanidine[19]
Aminoguanidine[7]
Azepan- (2Z)-ylideneamine[3]
Azocan- (2Z)-ylideneamine[3]
Azonan- (2Z)-ylideneamine[9]
B-Octylglucoside[7]
CDDO[20]
CURCUMIN[21]
Ethylisothiourea[7]
Heme[14]
Hexahydro-cyclopenta[c]pyrrol- (1Z)-ylideneamine[11]
Hydrocortisone[2]
Imidazole[17]
L-NIO[22]
L-Nw-nitroarginine[23]
L-Thiocitrulline[7]
N,N-dimethylarginine[24]
N- (3-[14]
N- (3-[10]
N- (5-Amino-6-oxo-heptyl)-acetamidine[11]
N-Omega-Hydroxy-L-Arginine[7]
N-Omega-Propyl-L-Arginine[7]
N-benzylacetimidamide hydrobromide[10]
N-omega-allyl-L-arginine[22]
N-omega-propargyl-L-arginine[22]
N5- (1-iminobut-3-enyl)-L-ornithine[22]
N5- (1-iminobutyl)-L-ornithine[22]
N5- (1-iminopropyl)-L-ornithine[22]
ONO-1714[4]
Octahydro-isoindol- (1Z)-ylideneamine[11]
Oxazolidin- (2Z)-ylideneamine[4]
Piperidin- (2E)-ylideneamine[6]
Pyrrolidin- (2Z)-ylideneamine[11]
Resveratrol Potassium4,-Sulfate[25]
S-Ethylisothiourea[7]
THIOCITRULLINE[26]
Thiazolidin- (2E)-ylideneamine[11]
Thiocoumarin[14]
[1,3]Oxazinan- (2E)-ylideneamine[9]
[1,3]Thiazinan- (2E)-ylideneamine[9]
[1,4]Oxazepan- (3E)-ylideneamine[5]
[1,4]Oxazepan- (5E)-ylideneamine[5]
[1,4]Thiazepan- (3E)-ylideneamine[5]
[1,4]Thiazepan- (5E)-ylideneamine[5]
[1,5]Thiazocan- (4E)-ylideneamine[3]
l-NIL[27]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Reperfusion injury in skeletal muscle is reduced in inducible nitric oxide synthase knockout mice. J Appl Physiol. 2004 Oct;97(4):1323-8. Epub 2004 Jun 4. To Reference
Ref 2Increased leukotriene concentrationx in submandibular glands from rats with experimental periodontitis. Inflamm Res. 2009 Apr 4. [Epub ahead of print] To Reference
Ref 3Bioorg Med Chem Lett. 2001 Oct 8;11(19):2651-3.Selective heterocyclic amidine inhibitors of human inducible nitric oxide synthase. To Reference
Ref 4Bioorg Med Chem Lett. 2004 Jan 19;14(2):313-6.4,5-Disubstituted-1,3-oxazolidin-2-imine derivatives: a new class of orally bioavailable nitric oxide synthase inhibitor. To Reference
Ref 5Bioorg Med Chem Lett. 2004 Dec 6;14(23):5907-11.Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases. To Reference
Ref 6Bioorg Med Chem Lett. 2005 Apr 15;15(8):1997-2001.Bicyclic amidine inhibitors of nitric oxide synthase: discovery of perhydro-iminopyrindine and perhydro-iminoquinoline as potent, orally active inhibitors of inducible nitric oxide synthase. To Reference
Ref 7Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 8J Med Chem. 2009 Apr 23;52(8):2443-53.Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine as a potential PET tracer for inducible nitric oxide synthase. To Reference
Ref 9J Med Chem. 1996 Feb 2;39(3):669-72.2-Iminopiperidine and other 2-iminoazaheterocycles as potent inhibitors of human nitric oxide synthase isoforms. To Reference
Ref 10Bioorg Med Chem Lett. 2010 Nov 15;20(22):6495-9. Epub 2010 Sep 17.N-Substituted acetamidines and 2-methylimidazole derivatives as selective inhibitors of neuronal nitric oxide synthase. To Reference
Ref 11Bioorg Med Chem Lett. 2004 Sep 6;14(17):4539-44.Evaluation of pyrrolidin-2-imines and 1,3-thiazolidin-2-imines as inhibitors of nitric oxide synthase. To Reference
Ref 12Bioorg Med Chem. 2008 Jun 1;16(11):5962-73. Epub 2008 Apr 26.Inhibitory effects of a series of 7-substituted-indazoles toward nitric oxide synthases: particular potency of 1H-indazole-7-carbonitrile. To Reference
Ref 13Bioorg Med Chem. 2009 Sep 1;17(17):6180-7. Epub 2009 Aug 6.Fluorinated indazoles as novel selective inhibitors of nitric oxide synthase (NOS): synthesis and biological evaluation. To Reference
Ref 14Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 15Nat Chem Biol. 2008 Nov;4(11):700-7. Epub 2008 Oct 12.Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase. To Reference
Ref 16Bioorg Med Chem Lett. 2009 Jan 1;19(1):74-6. Epub 2008 Nov 12.Synthesis of biflavones having a 6-O-7'' linkage and effects on cyclooxygenase-2 and inducible nitric oxide synthase. To Reference
Ref 17Nucleic Acids Res. 2011 January; 39(Database issue): D1035¨CD1041. DrugBank 3.0: a comprehensive resource for ¡®Omics¡¯ research on drugs To Reference
Ref 18Bioorg Med Chem Lett. 2008 Dec 1;18(23):6206-9. Epub 2008 Oct 5.The design, synthesis and biological evaluation of 7-alkoxy-4-heteroarylamino-3-cyanoquinolines as dual inhibitors of c-Src and iNOS. To Reference
Ref 19Inhibitory effects of aminoguanidine on thyroid follicular carcinoma development in inflamed capsular regions of rats treated with sulfadimethoxine after N-bis(2-hydroxypropyl)nitrosamine-initiation. Cancer Sci. 2009 Jul 1. [Epub ahead of print] To Reference
Ref 20Bioorg Med Chem Lett. 2005 May 2;15(9):2215-9.Studies on the reactivity of CDDO, a promising new chemopreventive and chemotherapeutic agent: implications for a molecular mechanism of action. To Reference
Ref 21Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. Epub 2007 Dec 11.A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. To Reference
Ref 22Bioorg Med Chem. 2008 Dec 15;16(24):10205-9. Epub 2008 Oct 29.Structure-activity relationship of novel and known inhibitors of human dimethylarginine dimethylaminohydrolase-1: alkenyl-amidines as new leads. To Reference
Ref 23J Med Chem. 2010 Nov 11;53(21):7804-24.Exploration of the active site of neuronal nitric oxide synthase by the design and synthesis of pyrrolidinomethyl 2-aminopyridine derivatives. To Reference
Ref 24van Guldener C, Nanayakkara PW, Stehouwer CD: Review: Homocysteine and asymmetric dimethylarginine (ADMA): biochemically linked but differently related to vascular disease in chronic kidney disease. Clin Chem Lab Med. 2007 Oct 15;. To Reference
Ref 25J Med Chem. 2010 Jul 8;53(13):5033-43.Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites. To Reference
Ref 26Bioorg Med Chem Lett. 2005 Jun 2;15(11):2881-5. Epub 2005 Apr 25.Evaluation of 3-substituted arginine analogs as selective inhibitors of human nitric oxide synthase isozymes. To Reference
Ref 27Bioorg Med Chem Lett. 2008 Jan 1;18(1):336-43. Epub 2007 Oct 25.Discovery of a series of aminopiperidines as novel iNOS inhibitors. To Reference



 

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Professor in Department of Pharmacy
National University of Singapore, Singapore


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