Therapeutic Targets Database
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TTD Target ID: TTDS00270

Target Information
NameMast/stem cell growth factor receptor    
Type of targetSuccessful target    
SynonymsC-kit    
CD117 antigen    
KIT    
Proto-oncogene tyrosine-protein kinase Kit    
SCFR    
DiseaseCancer, unspecific
[ICD9: 140-229   ICD10: C00-C96]
[1][2]
Gastrointestinal stromal tumors
[ICD9: 150-159   ICD10: C15-C26]
[3]
Inflammation[2]
Malignant phyllodes tumours
[ICD9: 140-199, 210-229   ICD10: C00-C75, C7A, C7B, D10-D36, D3A]
[4]
Ovarian cancer
[ICD9: 183   ICD10: C56]
[5]
Phyllodes tumours
[ICD9: 140-199, 210-229   ICD10: C00-C75, C7A, C7B, D10-D36, D3A]
[6]
Renal cell carcinoma
[ICD9: 189   ICD10: C64]
[7]
Small cell lung cancer
[ICD9: 162.9   ICD10: C34.90]
[4]
Drug(s)Pazopanib HClApprovedRenal cell carcinoma[8]
PonatinibApprovedChronic, accelerated or blast-phase chronic myeloid leukaemia
RegorafenibApprovedMetastatic colorectal cancer
ImatinibLaunchedChronic myelogenous leukemia [9]
SunitinibLaunchedAdvanced renal cell carcinoma[10][11][9][12]
Sunitinib malatePhase IVMetastatic Renal Cell Carcinoma; Gastrointestinal Stromal Tumors[13][14][9]
ImatinibPhase IIIIntestinal cancer & myeloid leukemia[9]
MotesanibPhase IIINon-small cell lung cancer[15][16][17]
NilotinibPhase IIILeukemia[9]
PazopanibPhase IIIAdvanced / metastatic renal cancer[9][18][19]
PazopanibPhase II completedSolid tumours, NSCLC[9][18][19]
ImatinibPhase IIGlioma, lung, prostate, solid tumours[9]
MotesanibPhase IIBreast cancer[15][16][17]
NilotinibPhase IIALL, CML, GIST[9]
PLX3397Phase IIAcute myeloid leukemia
PLX3397Phase IIGlioblastoma
PLX3397Phase IIGlioblastoma (GBM)
PLX3397Phase IIHodgkin lymphoma
PLX3397Phase IIMetastatic Breast cancer
PLX3397Phase IIMetastatic Prostate cancer
PLX3397Phase IIProstate Caner
SunitinibPhase IIAdvanced renal cell carcinoma[10][11][9][12]
Sunitinib malatePhase IISoft Tissue Sarcoma[13][14][9]
PLX3397Phase I/IIAcute myelogenous lymphoma (AML)
MP470Phase ISolid Tumors[20]
Motesanib diphosphatePhase IProgressive non-small cell lung cancer[21][16]
OSI-930Phase IVarious cancers[9]
BioChemical ClassTransferases transferring phosphorus-containing groups    
EC NumberEC 2.7.1.112
PathwayAcute myeloid leukemia
Cytokine-cytokine receptor interaction
Hematopoietic cell lineage
Melanogenesis
Pathways in cancer
UniProt IDP10721
PDB Structure1PKG; 1QZJ; 1QZK; 1R01; 1T45; 1T46; 2E9W; 2EC8; 2VIF; 3G0E; 3G0F; 4HVS.    
FunctionThis is the receptor for stem cell factor (mast cell growth factor). It has a tyrosine-protein kinase activity. binding of the ligands leads to the autophosphorylation of kit and its association with substrates such as phosphatidylinositol 3-kinase (pi3k).    
SequenceMRGARGAWDFLCVLLLLLRVQTGSSQPSVSPGEPSPPSIHPGKSDLIVRVGDEIRLLCTD PGFVKWTFEILDETNENKQNEWITEKAEATNTGKYTCTNKHGLSNSIYVFVRDPAKLFLV DRSLYGKEDNDTLVRCPLTDPEVTNYSLKGCQGKPLPKDLRFIPDPKAGIMIKSVKRAYH RLCLHCSVDQEGKSVLSEKFILKVRPAFKAVPVVSVSKASYLLREGEEFTVTCTIKDVSS SVYSTWKRENSQTKLQEKYNSWHHGDFNYERQATLTISSARVNDSGVFMCYANNTFGSAN VTTTLEVVDKGFINIFPMINTTVFVNDGENVDLIVEYEAFPKPEHQQWIYMNRTFTDKWE DYPKSENESNIRYVSELHLTRLKGTEGGTYTFLVSNSDVNAAIAFNVYVNTKPEILTYDR LVNGMLQCVAAGFPEPTIDWYFCPGTEQRCSASVLPVDVQTLNSSGPPFGKLVVQSSIDS SAFKHNGTVECKAYNDVGKTSAYFNFAFKGNNKEQIHPHTLFTPLLIGFVIVAGMMCIIV MILTYKYLQKPMYEVQWKVVEEINGNNYVYIDPTQLPYDHKWEFPRNRLSFGKTLGAGAF GKVVEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIVNLLGAC TIGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHAEAALYKNLLHSKESSCSDSTNE YMDMKPGVSYVVPTKADKRRSVRIGSYIERDVTPAIMEDDELALDLEDLLSFSYQVAKGM AFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWMAPES IFNCVYTFESDVWSYGIFLWELFSLGSSPYPGMPVDSKFYKMIKEGFRMLSPEHAPAEMY DIMKTCWDADPLKRPTFKQIVQLIEKQISESTNHIYSNLANCSPNRQKPVVDHSVRINSV GSTASSSQPLLVHDDV
Related US Patent6,642,232
Target ValidationClick to Find Target Validation Information.    
Inhibitor4- (4-aminophenyl)-1H-indazol-3yl-amine[22]
5,11-Dimethyl-6H-pyrido[4,3-b]carbazol-9-ol[23]
9-Bromo-5,11-dimethyl-6H-pyrido[4,3-b]carbazole[23]
9-Methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carbazole[23]
AZD-0530[24]
Adenosine-5'-Diphosphate[25]
Bis- (5-hydroxy-1H-indol-2-yl)-methanone[26]
ELLIPTINIUM[23]
Imatinib[9]
MP470[20]
Motesanib[15][16][17]
Motesanib diphosphate[21][16]
Nilotinib[9]
OSI-930[9]
PD-0166326,   PD-166326[27]
PD-0173956[27]
Pazopanib[9][18][19]
Pazopanib HCl[8]
Phosphonotyrosine[28]
SEMAXINIB[29]
Sunitinib[10][11][9][12]
Sunitinib malate[13][14][9]
MultitargetImatinib[9]
MP470[20]
Motesanib[15][16][17]
Motesanib diphosphate[21][16]
Nilotinib[9]
OSI-930[9]
Pazopanib[9][18][19]
Pazopanib HCl[8]
Sti-571[25]
Sunitinib[10][11][9][12]
Sunitinib malate[13][14][9]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Growth factor receptors as therapeutic targets: strategies to inhibit the insulin-like growth factor I receptor. Oncogene. 2003 Sep 29;22(42):6589-97. To Reference
Ref 2Hair depigmentation is a biological readout for pharmacological inhibition of KIT in mice and humans. J Pharmacol Exp Ther. 2003 Nov;307(2):476-80. Epub 2003 Sep 9. To Reference
Ref 3KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res. 2001 Nov 15;61(22):8118-21. To Reference
Ref 4CD117 (c-KIT) overexpression in patients with extensive-stage small-cell lung carcinoma. Ann Oncol. 2003 Jun;14(6):894-7. To Reference
Ref 5KIT in ovarian carcinoma: disillusion about a potential therapeutic target. J Natl Cancer Inst. 2003 Jul 2;95(13):1009-10. To Reference
Ref 6Malignant phyllodes tumours show stromal overexpression of c-myc and c-kit. J Pathol. 2003 May;200(1):59-64. To Reference
Ref 7Overexpression of KIT in chromophobe renal cell carcinoma. Oncogene. 2003 Feb 13;22(6):847-52. To Reference
Ref 8Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92. To Reference
Ref 9A 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 10FLT3 inhibition and mechanisms of drug resistance in mutant FLT3-positive AML. Drug Resist Updat. 2009 Jun;12(3):81-9. Epub 2009 May 20. To Reference
Ref 11FMS-like tyrosine kinase 3-internal tandem duplication tyrosine kinase inhibitors display a nonoverlapping profile of resistance mutations in vitro. Cancer Res. 2009 Apr 1;69(7):3032-41. Epub 2009 Mar 24. To Reference
Ref 12Multi-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 13Pfizer. Product Development Pipeline. March 31 2009. To Reference
Ref 14Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos. 2009 Feb;37(2):359-65. Epub 2008 Oct 29. To Reference
Ref 15Amgen. Product Development Pipeline. February 6 2009. To Reference
Ref 16Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol. 2009 Aug 10;27(23):3794-801. Epub 2009 Jun 29. To Reference
Ref 17Amgen. Report of Amgen. 2009. To Reference
Ref 18GSK. Product Development Pipeline. February 2009. To Reference
Ref 19Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy. Curr Opin Investig Drugs. 2008 Dec;9(12):1324-35. To Reference
Ref 20MP470, a novel receptor tyrosine kinase inhibitor, in combination with Erlotinib inhibits the HER family/PI3K/Akt pathway and tumor growth in prostate cancer. BMC Cancer. 2009 May 11;9:142. To Reference
Ref 21Takeda. Product Development Pipeline. July 31 2009. To Reference
Ref 22J Med Chem. 2007 Apr 5;50(7):1584-97. Epub 2007 Mar 8.Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor tyrosine kinase inhibitor. To Reference
Ref 23J Med Chem. 2005 Oct 6;48(20):6194-201.Molecular modeling of wild-type and D816V c-Kit inhibition based on ATP-competitive binding of ellipticine derivatives to tyrosine kinases. To Reference
Ref 24J 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 25Nucleic Acids Res. 2011 January; 39(Database issue): D1035¨CD1041. DrugBank 3.0: a comprehensive resource for ¡®Omics¡¯ research on drugs To Reference
Ref 26J Med Chem. 2006 Jun 1;49(11):3101-15.Novel bis(1H-indol-2-yl)methanones as potent inhibitors of FLT3 and platelet-derived growth factor receptor tyrosine kinase. To Reference
Ref 27Bioorg 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 28Overington 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 29J Med Chem. 2000 Jun 15;43(12):2310-23.New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis. To Reference



 

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