Target Validation Information
TTD ID	TTDS00407
Target Name	Proto-oncogene tyrosine-protein kinase LCK
Type of Target	Successful target
Drug Potency against Target	VX-680		Ki = 520 nM	[1]
	AZD-0530		IC50 < 4 nM	[2]
	PD-0166326;PD-166326		IC50 < 5 nM	[3]
	PD-0173952		IC50 < 5 nM	[3]
	PD-0173955;PD-17395		IC50 < 5 nM	[3]
	PD-0173958		IC50 < 5 nM	[3]
	PD-0180970		IC50 < 5 nM	[3]
	PD-0179483		IC50 < 5 nM	[3]
	PD-0173956		IC50 < 5 nM	[3]
	(4-Phenoxy-phenyl)-quinazolin-4-yl-amine		IC50 < 8 nM	[4]
	JNJ-10198409		IC50 = 100 nM	[5]
	4-(3-Chloro-phenoxy)-6,7-dimethoxy-quinazoline		IC50 = 1000 nM	[6]
	Y-c[D-Pen-(3,5-diI)Tyr-GSFC]KR-NH2		IC50 = 11000 nM	[7]
	Y-c[D-Pen-(3-I)Tyr-GSFC]KR-NH2		IC50 = 11000 nM	[7]
	A-770041		IC50 = 147 nM	[8]
	SU 6656		IC50 = 150 nM	[9]
	A-641359		IC50 = 20 nM	[8]
	CGP-57380		IC50 = 2500 nM	[9]
	2-(3,4,5-Trihydroxy-benzylidene)-malononitrile		IC50 = 3000 nM	[10]
	AG-1879		IC50 = 31 nM	[9]
	BMS-536924		IC50 = 341 nM	[11]
	A-420983		IC50 = 37 nM	[12]
	NM-PP1		IC50 = 460 nM	[9]
	RPR-108518A		IC50 = 500 nM	[6]
	ZM-336372		IC50 = 570 nM	[9]
	CEP-5104		IC50 = 6400 nM	[13]
	LAVENDUSTIN A		IC50 = 8000 nM	[14]
	3-(4-(o-toluidino)pyrimidin-2-ylamino)benzamide		IC50 = 89 nM	[15]
	6-o-tolylquinazolin-2-amine		IC50 = 94 nM	[16]
	AZD-1152-HQPA;Barasertib		Ki = 170 nM	[17]
	TG-100435		Ki = 29.4 nM	[18]
Ref 1	Nat Med. 2004 Mar;10(3):262-7. Epub 2004 Feb 22.VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. To Reference
Ref 2	J 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 3	Biochem 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 4	Bioorg 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 5	J 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 6	Bioorg. Med. Chem. Lett. 7(4):417-420 (1997) To Reference
Ref 7	J 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
Ref 8	Bioorg 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 9	Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update. To Reference
Ref 10	J 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 11	J 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 12	Bioorg 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 13	J 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 14	J Med Chem. 1993 Oct 1;36(20):3010-4.Non-amine based analogues of lavendustin A as protein-tyrosine kinase inhibitors. To Reference
Ref 15	Bioorg 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 16	J 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 17	J 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 18	Bioorg 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

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Dr. Chen Yuzong
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Professor in Department of Pharmacy
National University of Singapore, Singapore

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