TTD Target ID: TTDR00224

Target Information
Name	Proliferating cell nuclear antigen
Type of target	Research target
Synonyms	Cyclin
	PCNA
Disease	Cardiovascular disease, unspecified    [1]
Pathway	Base excision repair
	Cell cycle
	DNA replication
	Mismatch repair
	Nucleotide excision repair
UniProt ID	P12004
PDB Structure	1AXC; 1U76; 1U7B; 1UL1; 1VYJ; 1VYM; 1W60; 2ZVK.
Function	This protein is an auxiliary protein of dna polymerase delta and is involved in the control of eukaryotic dna replication by increasing the polymerase's processibility during elongation of the leading strand.
Sequence	MFEARLVQGSILKKVLEALKDLINEACWDISSSGVNLQSMDSSHVSLVQLTLRSEGFDTY RCDRNLAMGVNLTSMSKILKCAGNEDIITLRAEDNADTLALVFEAPNQEKVSDYEMKLMD LDVEQLGIPEQEYSCVVKMPSGEFARICRDLSHIGDAVVISCAKDGVKFSASGELGNGNI KLSQTSNVDKEEEAVTIEMNEPVQLTFALRYLNFFTKATPLSSTVTLSMSADVPLVVEYK IADMGHLKYYLAPKIEDEEGS
Target Validation	Click to Find Target Validation Information.
Inhibitor	2,5-dichloro-N-p-tolylthiophene-3-sulfonamide		[2]
	3- (		[3]
	4- (7-Butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenol		[4]
	4- (phenyldiazenyl)-1H-pyrazole-3,5-diamine		[3]
	4-[ (3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol		[3]
	6- (3-Amino-benzyloxy)-9H-purin-2-ylamine		[5]
	6- (3-Methyl-benzyloxy)-9H-purin-2-ylamine		[5]
	6- (Cyclohex-3-enylmethoxy)-9H-purin-2-ylamine		[5]
	6-Cyclohexylmethoxy-pyrimidine-2,4,5-triamine		[6]
	GW-8510		[7]
	MERIOLIN 1		[8]
	MERIOLIN 2		[8]
	MERIOLIN 3		[8]
	MERIOLIN 4		[8]
	MERIOLIN 5		[8]
	MERIOLIN 6		[8]
	MERIOLIN 7		[8]
	MERIOLIN 8		[8]
	NU-2058		[9]
	NU-6027		[6]
	PD-0183812		[10]
	PURVALANOLA		[11]
	RESCOVITINE		[12]
	SB-216763		[13]
Cross References	3D Structure Related Literature On-Line Medical Dictionary
Ref 1	Apoptosis and proliferation of cardiomyocytes in heart failure of different etiologies. Cardiovasc Pathol. 2000 May-Jun;9(3):149-52. To Reference
Ref 2	Bioorg. Med. Chem. Lett. 20(13):3863-3867 (2010) To Reference
Ref 3	J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. To Reference
Ref 4	J Med Chem. 2003 Jan 16;46(2):222-36.Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. To Reference
Ref 5	J Med Chem. 2002 Aug 1;45(16):3381-93.Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O(6)-substituted guanine derivatives. To Reference
Ref 6	Bioorg Med Chem Lett. 2003 Jan 20;13(2):217-22.4-Alkoxy-2,6-diaminopyrimidine derivatives: inhibitors of cyclin dependent kinases 1 and 2. To Reference
Ref 7	Bioorg Med Chem Lett. 2004 Feb 23;14(4):953-7.Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles. To Reference
Ref 8	J Med Chem. 2008 Feb 28;51(4):737-51. Epub 2008 Jan 31.Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin complex. To Reference
Ref 9	J Med Chem. 2004 Jul 15;47(15):3710-22.N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2. To Reference
Ref 10	J Med Chem. 2000 Nov 30;43(24):4606-16.Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. To Reference
Ref 11	Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update. To Reference
Ref 12	Eur J Med Chem. 2010 Mar;45(3):1158-66. Epub 2009 Dec 21.Design, synthesis, and biological evaluation of novel pyrimidine derivatives as CDK2 inhibitors. To Reference
Ref 13	J Med Chem. 2010 Feb 11;53(3):994-1003.Benzo[e]isoindole-1,3-diones as potential inhibitors of glycogen synthase kinase-3 (GSK-3). Synthesis, kinase inhibitory activity, zebrafish phenotype, and modeling of binding mode. To Reference

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Professor in Department of Pharmacy
National University of Singapore, Singapore

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