Therapeutic Targets Database
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TTD Target ID: TTDS00247

Target Information
NameProto-oncogene tyrosine-protein kinase SRC    
Type of targetSuccessful target    
SynonymsC-SRC tyrosine kinase    
C-Src    
C-src TK    
P60-Src    
Pp60(src)    
Src tyrosine kinase    
Tyrosine kinase    
Tyrosine kinase (pp60(src))    
DiseaseBreast cancer
[ICD9: 174, 175   ICD10: C50]
[1]
Cancer, unspecific
[ICD9: 140-229   ICD10: C00-C96]
[2][3]
Osteoporosis and other bone-related diseases
[ICD9: 733.0   ICD10: M80-M81]
[4]
Osteoporosis, unspecified
[ICD9: 733.0   ICD10: M80-M81]
[5]
Drug(s)Herbimycin AApprovedCancer[6]
DasatinibLaunchedChronic myelogenous leukemia [7][8][9]
AZD0530Phase IIOsteosarcoma; Hematological malignancies, solid tumours[7][10]
DasatinibPhase IISolid tumours, multiple myeloma[7][8][9]
BosutinibPhase I/IIAdvanced Breast Cancer[7]
KX01Phase IAML, CML
KX01Phase IAcute myeloid leukemia
BioChemical ClassTransferases transferring phosphorus-containing groups    
EC NumberEC 2.7.1.112
PathwayAdherens junction
Epithelial cell signaling in Helicobacter pylori
ErbB signaling pathway
Focal adhesion
Gap junction
GnRH signaling pathway
Tight junction
VEGF signaling pathway
UniProt IDP12931
PDB Structure1A07; 1A08; 1A09; 1A1A; 1A1B; 1A1C; 1A1E; 1FMK; 1HCS; 1HCT; 1KSW; 1O41; 1O42; 1O43; 1O44; 1O45; 1O46; 1O47; 1O48; 1O49; 1O4A; 1O4B; 1O4C; 1O4D; 1O4E; 1O4F; 1O4G; 1O4H; 1O4I; 1O4J; 1O4K; 1O4L; 1O4M; 1O4N; 1O4O; 1O4P; 1O4Q; 1O4R; 1SHD; 1Y57; 1YI6; 1YOJ; 1YOL; 1YOM; 2BDF; 2BDJ; 2H8H; 2SRC; 3VRO; 4F59; 4F5A; 4F5B; 4HXJ.    
SequenceMGSNKSKPKDASQRRRSLEPAENVHGAGGGAFPASQTPSKPASADGHRGPSAAFAPAAAE PKLFGGFNSSDTVTSPQRAGPLAGGVTTFVALYDYESRTETDLSFKKGERLQIVNNTEGD WWLAHSLSTGQTGYIPSNYVAPSDSIQAEEWYFGKITRRESERLLLNAENPRGTFLVRES ETTKGAYCLSVSDFDNAKGLNVKHYKIRKLDSGGFYITSRTQFNSLQQLVAYYSKHADGL CHRLTTVCPTSKPQTQGLAKDAWEIPRESLRLEVKLGQGCFGEVWMGTWNGTTRVAIKTL KPGTMSPEAFLQEAQVMKKLRHEKLVQLYAVVSEEPIYIVTEYMSKGSLLDFLKGETGKY LRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYT ARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVER GYRMPCPPECPESLHDLMCQCWRKEPEERPTFEYLQAFLEDYFTSTEPQYQPGENL
Related US Patent6,316,444
6,329,380
6,498,165
6,503,914
6,642,227
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
Inhibitor2- (4-CARCOXY-5-ISOPROPYLTHIAZOLYL)BENZOPIPERIDINE[11]
3- (3-aminobenzo[e][1,2,4]triazin-7-yl)phenol[12]
4-Chloro-5,7-diphenyl-7H-pyrrolo[2,3-d]pyrimidine[13]
5,7-Diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-ol[13]
7- (naphthalen-2-yl)benzo[e][1,2,4]triazin-3-amine[12]
A-420983[14]
A-770041[15]
AG-1879[16]
AP-24163[17]
AP-24226[17]
AP22408[4]
AZD-0530[18]
AZD0530[7][10]
Ac-Cys-Ile-Phe (4-NO2)-Lys-Phe[19]
Ac-Cys-Ile-Phe (4-NO2)-Lys-Tyr-Phe[19]
Ac-Cys-Ile-Phe (4-NO2)-Lys-Tyr-Tyr[19]
Ac-Cys-Ile-Tyr-Lys-Phe (4-CN)-Tyr[19]
Ac-Cys-Ile-Tyr-Lys-Phe (4-Cl)-Tyr[19]
Ac-Cys-Ile-Tyr-Lys-Phe (4-I)-Tyr[19]
Ac-Cys-Ile-Tyr-Lys-Phe (4-N3)-Tyr[19]
Ac-Cys-Ile-Tyr-Lys-Phe (4-NO2)-Phe[19]
Ac-Cys-Ile-Tyr-Lys-Phe (4-NO2)-Tyr-Phe[19]
Ac-Cys-Ile-Tyr-Lys-Tyr-Phe (4-NO2)[19]
Ac-Cys-Ile-cyclo[Phe-Lys]-Tyr-Tyr[19]
Ac-Cys-Ile-cyclo[Phe-Lys]-Tyr-Tyr[19]
BAS-00387275[20]
BAS-00387328[20]
BAS-00387347[20]
BAS-00672722[20]
BAS-01047341[20]
BAS-01047655[20]
BAS-01373578[20]
BAS-0338868[21]
BAS-0338872[21]
BAS-09534324[20]
BAS-450225[20]
BAS-4844343[20]
BMS-279700[22]
Bosutinib[7]
CGP 77675[23]
CGP-191[13]
CGP-62464[13]
Cyclo[Ac-Cys-Ile-Phe]-Lys-Tyr-Tyr[19]
Cyclo[Ac-Cys-Ile-Tyr-Lys-Tyr-Phe][19]
Cyclo[Ac-Cys-Ile-Tyr-Lys-Tyr-Tyr][19]
Cysteine Sulfenic Acid[24]
DPI59[11]
Dasatinib[7][8][9]
Glu-Pro-Gln-F2Pmp-Glu-Glu-Ile-Pro-Ile-Tyr-Leu[25]
Glu-Pro-Gln-pTyr-Glu-Glu-Ile-Pro-Ile-Tyr-Leu[25]
Herbimycin A[6]
ISO24[11]
JNJ-10198409[26]
Malonic acid[27]
N- (4-PHENYLAMINO-QUINAZOLIN-6-YL)-ACRYLAMIDE[11]
N-Phenyl-5-phenylimidazo[1,5-a]pyrazin-8-amine[22]
N6-Benzyl Adenosine-5'-Diphosphate[27]
NM-PP1[16]
Oxalic Acid[27]
PAS219[11]
PASBN[11]
PD-0166326,   PD-166326[28]
PD-0173952[29]
PD-0173955,   PD-17395[29]
PD-0173956[28]
PD-0173958[29]
PD-0179483[29]
PD-0180970[29]
PD-174265[30]
PD166285[31]
PD173074[31]
Phenylphosphate[24]
Phosphonotyrosine[27]
Purvalanol A[11]
RU78191[11]
RU78262[11]
RU78299[11]
RU78300[11]
RU78783[27]
RU79072[11]
RU79073[11]
RU79256[11]
RU81843[27]
RU82129[27]
RU82197[24]
RU82209[27]
RU83876[27]
RU84687[11]
RU85053[27]
RU85493[27]
RU90395[27]
SB-203580[32]
SKI-758[33]
SKS-927[34]
SU 6656[16]
TG-100435[35]
Y-c[D-Pen- (2')Nal-GSFC]KR-NH2[36]
Y-c[D-Pen- (2R,3R)-2-Me-[36]
Y-c[D-Pen- (2R,3S)-2-Me-[36]
Y-c[D-Pen- (2S,3R)-2-Me-[36]
Y-c[D-Pen- (2S,3S)-2-Me-[36]
Y-c[D-Pen- (3,5-diI)Tyr-GSFC]KR-NH2[36]
Y-c[D-Pen- (3-I)Tyr-GSFC]KR-NH2[36]
Y-c[D-Pen-D- (2')Nal-GSFC]KR-NH2[36]
MultitargetAZD0530[7][10]
Bosutinib[7]
Dasatinib[7][8][9]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1C-SRC tyrosine kinase activity is associated with tumor colonization in bone and lung in an animal model of human breast cancer metastasis. Cancer Res. 2003 Aug 15;63(16):5028-33. To Reference
Ref 2Src in cancer: deregulation and consequences for cell behaviour. Biochim Biophys Acta. 2002 Jun 21;1602(2):114-30. To Reference
Ref 3Cancer metastasis therapeutic targets and drug discovery: emerging small-molecule protein kinase inhibitors. Expert Opin Investig Drugs. 2004 Jan;13(1):1-19. To Reference
Ref 4Structure-based design of an osteoclast-selective, nonpeptide src homology 2 inhibitor with in vivo antiresorptive activity. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9373-8. To Reference
Ref 5Src inhibitors: genomics to therapeutics. Expert Opin Investig Drugs. 2001 Jul;10(7):1327-44. To Reference
Ref 6In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABL-transfected cells. Leuk Res. 1994 Nov;18(11):867-73. To Reference
Ref 7A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. To Reference
Ref 8In vitro and clinical investigation of the relationship between CCR5 receptor occupancy and anti-HIV activity of Aplaviroc. J Clin Pharmacol. 2008 Oct;48(10):1179-88. Epub 2008 Aug 1. To Reference
Ref 9Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42. Epub 2006 Nov 28. To Reference
Ref 10AstraZeneca. Product Development Pipeline. January 29 2009. To Reference
Ref 11Berman 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 12Bioorg Med Chem Lett. 2006 Nov 1;16(21):5546-50. Epub 2006 Aug 22.Discovery and preliminary structure-activity relationship studies of novel benzotriazine based compounds as Src inhibitors. To Reference
Ref 13Bioorg Med Chem Lett. 2000 May 1;10(9):945-9.Substituted 5,7-diphenyl-pyrrolo[2,3d]pyrimidines: potent inhibitors of the tyrosine kinase c-Src. To Reference
Ref 14Bioorg Med Chem Lett. 2004 May 17;14(10):2613-6.A-420983: a potent, orally active inhibitor of lck with efficacy in a model of transplant rejection. To Reference
Ref 15Bioorg Med Chem Lett. 2006 Jan 1;16(1):118-22. Epub 2005 Oct 10.Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection. To Reference
Ref 16Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update. To Reference
Ref 17J Med Chem. 2009 Aug 13;52(15):4743-56.9-(Arenethenyl)purines as dual Src/Abl kinase inhibitors targeting the inactive conformation: design, synthesis, and biological evaluation. To Reference
Ref 18J Med Chem. 2006 Nov 2;49(22):6465-88.N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. To Reference
Ref 19J Med Chem. 2006 Jun 1;49(11):3395-401.Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as Src tyrosine kinase inhibitors. To Reference
Ref 20J Med Chem. 2006 Jun 1;49(11):3278-86.A combination of docking/dynamics simulations and pharmacophoric modeling to discover new dual c-Src/Abl kinase inhibitors. To Reference
Ref 21Bioorg Med Chem Lett. 2008 Feb 1;18(3):1207-11. Epub 2007 Dec 4.Discovery and SAR of 1,3,4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents. To Reference
Ref 22Bioorg Med Chem. 2007 Jan 15;15(2):868-85. Epub 2006 Oct 24.Synthesis and c-Src inhibitory activity of imidazo[1,5-a]pyrazine derivatives as an agent for treatment of acute ischemic stroke. To Reference
Ref 23A novel inhibitor of the tyrosine kinase Src suppresses phosphorylation of its major cellular substrates and reduces bone resorption in vitro and in rodent models in vivo. Bone. 1999 May;24(5):437-49. To Reference
Ref 24Nucleic Acids Res. 2011 January; 39(Database issue): D1035¨CD1041. DrugBank 3.0: a comprehensive resource for ¡®Omics¡¯ research on drugs To Reference
Ref 25Bioorg. Med. Chem. Lett. 7(14):1909-1914 (1997) To Reference
Ref 26J Med Chem. 2005 Dec 29;48(26):8163-73.(6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines: platelet-derived growth factor receptor tyrosine kinase inhibitors with broad antiproliferative activity against tumor cells. To Reference
Ref 27Overington 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 28Bioorg Med Chem Lett. 2009 Dec 15;19(24):6872-6. Epub 2009 Oct 23.Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors. To Reference
Ref 29Biochem Pharmacol. 2000 Oct 1;60(7):885-98.Biochemical and cellular effects of c-Src kinase-selective pyrido[2, 3-d]pyrimidine tyrosine kinase inhibitors. To Reference
Ref 30J Med Chem. 2009 Jul 9;52(13):3915-26.Hybrid compound design to overcome the gatekeeper T338M mutation in cSrc. To Reference
Ref 31Anti-angiogenic activity of selected receptor tyrosine kinase inhibitors, PD166285 and PD173074: implications for combination treatment with photodynamic therapy. Invest New Drugs. 1999;17(2):121-35. To Reference
Ref 32J Med Chem. 2005 Jun 16;48(12):4138-52.Rapid computational identification of the targets of protein kinase inhibitors. To Reference
Ref 33J Med Chem. 2006 Dec 28;49(26):7868-76.Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. To Reference
Ref 34Bioorg Med Chem Lett. 2007 Mar 1;17(5):1358-61. Epub 2006 Dec 3.Inhibition of Src kinase activity by 7-ethynyl-4-phenylamino-3-quinolinecarbonitriles: identification of SKS-927. To Reference
Ref 35Bioorg Med Chem Lett. 2007 Feb 1;17(3):602-8. Epub 2006 Nov 7.Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays. To Reference
Ref 36J Med Chem. 1998 Jun 18;41(13):2252-60.Discovery of a novel series of potent and selective substrate-based inhibitors of p60c-src protein tyrosine kinase: conformational and topographical constraints in peptide design. To Reference



 

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Professor in Department of Pharmacy
National University of Singapore, Singapore


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