Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
   

 

TTD Target ID: TTDS00407

Target Information
NameProto-oncogene tyrosine-protein kinase LCK    
Type of targetSuccessful target    
SynonymsFYN    
Protooncogene Syn    
SLK    
p59-Fyn    
DiseasePhiladelphia-positive leukemia
[ICD9: 208.9   ICD10: C91-C95]
[1]
Drug(s)DasatinibLaunchedChronic myelogenous leukemia [2][3][4]
DasatinibPhase IISolid tumours, multiple myeloma[2][3][4]
VX-680Terminated in Phase IChronic Myelogenous Leukemia; Leukemia; Lymphoblastic, Acute, Philadelphia-Positive[2][5]
VX-680Terminated in Phase IILeukemia[2][5]
BioChemical ClassTransferases transferring phosphorus-containing groups    
PathwayNatural killer cell mediated cytotoxicity
Primary immunodeficiency
T cell receptor signaling pathway
UniProt IDP06239
PDB Structure1FBZ; 1H92; 1IJR; 1KIK; 1LCJ; 1LCK; 1LKK; 1LKL.    
SequenceMGCGCSSHPEDDWMENIDVCENCHYPIVPLDGKGTLLIRNGSEVRDPLVTYEGSNPPASP LQDNLVIALHSYEPSHDGDLGFEKGEQLRILEQSGEWWKAQSLTTGQEGFIPFNFVAKAN SLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKH YKIRNLDNGGFYISPRITFPGLHELVRHYTNASDGLCTRLSRPCQTQKPQKPWWEDEWEV PRETLKLVERLGAGQFGEVWMGYYNGHTKVAVKSLKQGSMSPDAFLAEANLMKQLQHQRL VRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNY IHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIK SDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMVRPDNCPEELYQLMRLCWKER PEDRPTFDYLRSVLEDFFTATEGQYQPQP
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
Inhibitor (4-Phenoxy-phenyl)-quinazolin-4-yl-amine[6]
2- (3,4,5-Trihydroxy-benzylidene)-malononitrile[7]
3- (4-[8]
4,5,6,7-tetrabromobenzotriazole[9]
4- (3-Chloro-phenoxy)-6,7-dimethoxy-quinazoline[10]
4-Phenylsulfanyl-7H-pyrrolo[2,3-d]pyrimidine[11]
6-o-tolylquinazolin-2-amine[12]
A-420983[13]
A-641359[14]
A-770041[14]
AG-1879[15]
AZD-0530[16]
AZD-1152-HQPA,   Barasertib[17]
BIRB796[18]
BISINDOLYLMALEIMIDE IX[19]
BMS-536924[20]
CEP-5104[21]
CGP-57380[15]
CI-1040,   PD-18435,   PD-184352[19]
Dasatinib[2][3][4]
GF-109203[19]
GW-788388[22]
Go-6976[19]
JNJ-10198409[23]
KN-62[19]
L-779450[24]
LAVENDUSTIN A[25]
LY-294002[19]
NM-PP1[15]
PD-0166326,   PD-166326[26]
PD-0173952[26]
PD-0173955,   PD-17395[26]
PD-0173956[26]
PD-0173958[26]
PD-0179483[26]
PD-0180970[26]
PD-98059[19]
Phosphoaminophosphonic Acid-Adenylate Ester[27]
RO-316233[19]
RPR-108518A[10]
SB-202190[18]
SB-203580[18]
STAUROSPORINONE[19]
SU 6656[15]
Staurosporine[28]
TG-100435[29]
U-0126[19]
VX-680[2][5]
Y-c[D-Pen- (3,5-diI)Tyr-GSFC]KR-NH2[30]
Y-c[D-Pen- (3-I)Tyr-GSFC]KR-NH2[30]
ZM-336372[15]
MultitargetDasatinib[2][3][4]
VX-680[2][5]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Philadelphia-positive patients who already harbour imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors. Blood. 2009 Jul 9. [Epub ahead of print] To Reference
Ref 2A 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 3In 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 4Multi-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 5Essential roles of mTOR/Akt pathway in Aurora-A cell transformation. Int J Biol Sci. 2009 Jun 19;5(5):444-50. To Reference
Ref 6Bioorg Med Chem Lett. 2000 Oct 2;10(19):2167-70.Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck I. To Reference
Ref 7J Med Chem. 1993 Nov 12;36(23):3556-64.Tyrphostins. 3. Structure-activity relationship studies of alpha-substituted benzylidenemalononitrile 5-S-aryltyrphostins. To Reference
Ref 8Bioorg Med Chem Lett. 2007 Aug 1;17(15):4363-8. Epub 2007 Apr 13.N-4-Pyrimidinyl-1H-indazol-4-amine inhibitors of Lck: indazoles as phenol isosteres with improved pharmacokinetics. To Reference
Ref 9J Med Chem. 2004 Dec 2;47(25):6239-47.Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. To Reference
Ref 10Bioorg. Med. Chem. Lett. 7(4):417-420 (1997) To Reference
Ref 11J Med Chem. 2005 Feb 10;48(3):710-22.Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. To Reference
Ref 12J Med Chem. 2006 Sep 21;49(19):5671-86.Discovery of aminoquinazolines as potent, orally bioavailable inhibitors of Lck: synthesis, SAR, and in vivo anti-inflammatory activity. To Reference
Ref 13Bioorg 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 14Bioorg 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 15Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update. To Reference
Ref 16J 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 17J Med Chem. 2007 May 3;50(9):2213-24. Epub 2007 Mar 21.Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase. To Reference
Ref 18J Med Chem. 2008 Jul 24;51(14):4122-49. Epub 2008 Jun 26.Design, synthesis, and biological evaluation of novel Tri- and tetrasubstituted imidazoles as highly potent and specific ATP-mimetic inhibitors of p38 MAP kinase: focus on optimized interactions with the enzyme's surface-exposed front region. To Reference
Ref 19Biochem J. 2000 Oct 1;351(Pt 1):95-105.Specificity and mechanism of action of some commonly used protein kinase inhibitors. To Reference
Ref 20J Med Chem. 2005 Sep 8;48(18):5639-43.Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. To Reference
Ref 21J Med Chem. 2008 Sep 25;51(18):5680-9. Epub 2008 Aug 21.Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models. To Reference
Ref 22J Med Chem. 2006 Apr 6;49(7):2210-21.Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orally active transforming growth factor-beta type I receptor inhibitor. To Reference
Ref 23J 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 24Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81. Epub 2005 Nov 2.The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. To Reference
Ref 25J Med Chem. 1993 Oct 1;36(20):3010-4.Non-amine based analogues of lavendustin A as protein-tyrosine kinase inhibitors. To Reference
Ref 26Biochem 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 27Berman 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 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 29Bioorg 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 30J 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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