Therapeutic Targets Database
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TTD Target ID: TTDC00162

Target Information
NameGlycogen synthase kinase-3 beta    
Type of targetClinical trial target    
SynonymsGSK-3 beta    
DiseaseAlzheimer's disease    [1]
Bipolar affective disorder    [1]
Brain injury    [1]
Immunodeficiency    [1]
Ischemia    [1]
Noninsulin-dependent diabetes mellitus    [1]
Drug(s)EnzastaurinPhase IIINon Hodgkin Lymphoma[2][3]
EnzastaurinPhase IIGlioblastoma Multiforme[2][3]
EnzastaurinPhase IBrain and Central Nervous System Tumors[2][3]
BioChemical ClassTransferases transferring phosphorus-containing groups    
EC NumberEC 2.7.1.37
PathwayAlzheimer's disease
Axon guidance
B cell receptor signaling pathway
Basal cell carcinoma
Cell cycle
Chemokine signaling pathway
Colorectal cancer
Endometrial cancer
ErbB signaling pathway
Focal adhesion
Hedgehog signaling pathway
Insulin signaling pathway
Melanogenesis
Pathways in cancer
Prostate cancer
T cell receptor signaling pathway
Wnt signaling pathway
UniProt IDP49841
PDB Structure1GNG; 1H8F; 1I09; 1J1B; 1J1C; 1O9U; 1PYX; 1Q3D.    
FunctionParticipates in the wnt signaling pathway. Implicated in the hormonal control of several regulatory proteins including glycogen synthase, myb, and the transcription factor c-jun. Phosphorylates c-jun at sites proximal to its dna-binding domain.    
SequenceMSGRPRTTSFAESCKPVQQPSAFGSMKVSRDKDGSKVTTVVATPGQGPDRPQEVSYTDTK VIGNGSFGVVYQAKLCDSGELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSG EKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHSFGICHR DIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDV WSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHP WTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFFDELRDPNVKLPNGRDTPALF NFTTQELSSNPPLATILIPPHARIQAAASTPTNATAASDANTGDRGQTNNAASASASNST
Related US Patent6,479,490
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
Inhibitor (2'Z,3'E)-7-Azaindirubin-3'-oxime[4]
(E)-N-[5]
12,13-DEHYDRO-8-O-ACETYLMANZAMINE A[6]
12,13-DEHYDROMANZAMINE A[6]
3- (6-[7]
3-phenyl-4- (phenylamino)-1H-pyrrole-2,5-dione[8]
4,5,6,7-tetrabromobenzotriazole[9]
4- (5-bromo-1H-indol-3-yl)pyrimidin-2-amine[10]
4-[ (3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol[11]
6-deoxymanzamine X[6]
6-hydroxymanzamine A[6]
8-O- (4-bromobenzenesulfonyl)manzamine F[6]
8-O- (4-chlorobenzenesulfonyl)manzamine F[6]
8-O- (4-toluenesulfonyl)manzamine A[6]
8-OH-MANZAMINE A[12]
9-N-ETHYL-8-ETHOXY-MANZAMINE A[6]
9-N-METHYL-8-METHOXY-MANZAMINE A[6]
AR-A014418[10]
AS-601245[13]
AZAKENPAULLONE[14]
Adenosine-5'-Diphosphate[15]
Alsterpaullone[16]
BISINDOLYLMALEIMIDE IX[17]
CHIR-98023,   CT-98014[10]
CI-1040,   PD-18435,   PD-184352[17]
CT-98024[18]
ELLAGIC ACID[19]
Enzastaurin[2][3]
GF-109203[17]
GSK-690693[20]
I-5[21]
Indirubin-3'-Monoxime[16]
KENPAULLONE[14]
L-779450[22]
LEUCETTAMINE B[23]
LY-294002[17]
MANZAMINE A[24]
N,8-diphenyl-9H-purin-6-amine[7]
N- (6-[5]
N- (6-[5]
N- (6-[5]
N- (6-[5]
N- (6-[5]
N- (6-[5]
N- (6-[25]
N- (6-[5]
N- (6-[5]
N- (6-[5]
N- (6-benzyl-1H-indazol-3-yl)butyramide[5]
N- (6-bromo-1H-indazol-3-yl)butyramide[5]
N- (6-chloro-1H-indazol-3-yl)butyramide[5]
N- (6-chloro-5-p-tolyl-1H-indazol-3-yl)butyramide[5]
N- (6-chloro-5-phenyl-1H-indazol-3-yl)butyramide[25]
N- (6-phenethyl-1H-indazol-3-yl)butyramide[5]
N- (6-phenyl-1H-indazol-3-yl)butyramide[25]
N- (8-[7]
NU-6102[26]
Neo-kauluamine[12]
PAULLONE[18]
PD-98059[17]
PF-228[27]
PYRAZOLOPYRIDAZINE 1[28]
PYRAZOLOPYRIDAZINE 2[28]
Phosphoaminophosphonic Acid-Adenylate Ester[29]
RO-320432[18]
SB-202190[17]
SB-203580[17]
SB-216763[30]
SB-415286[18]
SB-415286[10]
STAUROSPORINONE[17]
Staurosporine[21]
TWS-119[31]
Thieno analogue of kenpaullone[14]
U-0126[17]
manzamine E[12]
manzamine Y[12]
MultitargetEnzastaurin[2][3]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. To Reference
Ref 2Enzastaurin shows preclinical antitumor activity against human transitional cell carcinoma and enhances the activity of gemcitabine. Mol Cancer Ther. 2009 Jul;8(7):1772-8. Epub 2009 Jun 9. To Reference
Ref 3A 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 4J Nat Prod. 2009 Dec;72(12):2199-202.Synthesis and antiproliferative activity of 7-azaindirubin-3'-oxime, a 7-aza isostere of the natural indirubin pharmacophore. To Reference
Ref 5Bioorg Med Chem Lett. 2010 Mar 15;20(6):1985-9. Epub 2010 Jan 25.Rational design of potent GSK3beta inhibitors with selectivity for Cdk1 and Cdk2. To Reference
Ref 6J Nat Prod. 2007 Sep;70(9):1397-405. Epub 2007 Aug 21.Glycogen synthase kinase-3 (GSK-3) inhibitory activity and structure-activity relationship (SAR) studies of the manzamine alkaloids. Potential for Alzheimer's disease. To Reference
Ref 7Eur J Med Chem. 2010 Aug;45(8):3389-93. Epub 2010 Apr 28.Novel 8-arylated purines as inhibitors of glycogen synthase kinase. To Reference
Ref 8Bioorg Med Chem. 2008 Jan 15;16(2):636-43. Epub 2007 Oct 22.Novel GSK-3beta inhibitors from sequential virtual screening. 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 10Eur J Med Chem. 2009 Jun;44(6):2361-71. Epub 2008 Sep 16.Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. To Reference
Ref 11J 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 12J Nat Prod. 2006 Jul;69(7):1034-40.Manzamine B and E and ircinal A related alkaloids from an Indonesian Acanthostrongylophora sponge and their activity against infectious, tropical parasitic, and Alzheimer's diseases. To Reference
Ref 13Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update. To Reference
Ref 14Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. To Reference
Ref 15Nucleic Acids Res. 2011 January; 39(Database issue): D1035¨CD1041. DrugBank 3.0: a comprehensive resource for ¡®Omics¡¯ research on drugs To Reference
Ref 16Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. To Reference
Ref 17Biochem J. 2000 Oct 1;351(Pt 1):95-105.Specificity and mechanism of action of some commonly used protein kinase inhibitors. To Reference
Ref 18Bioorg Med Chem Lett. 2010 Mar 1;20(5):1693-6. Epub 2010 Jan 25.Discovery of potent and bioavailable GSK-3beta inhibitors. To Reference
Ref 19J Med Chem. 2006 Apr 20;49(8):2363-6.Identification of ellagic acid as potent inhibitor of protein kinase CK2: a successful example of a virtual screening application. To Reference
Ref 20Bioorg Med Chem Lett. 2009 Mar 1;19(5):1508-11. Epub 2009 Jan 9.Aminofurazans as potent inhibitors of AKT kinase. To Reference
Ref 21Overington 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 22Bioorg 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 23Eur J Med Chem. 2010 Feb;45(2):805-10. Epub 2009 Oct 12.Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid leucettamine B as kinase inhibitors. To Reference
Ref 24Bioorg Med Chem. 2008 Jul 15;16(14):6702-6. Epub 2008 Jun 5.2-N-Methyl modifications and SAR studies of manzamine A. To Reference
Ref 25Bioorg Med Chem Lett. 2010 Apr 1;20(7):2344-9. Epub 2010 Feb 2.Design of potent and selective GSK3beta inhibitors with acceptable safety profile and pharmacokinetics. To Reference
Ref 26Bioorg Med Chem Lett. 2006 Mar 1;16(5):1353-7. Epub 2005 Dec 1.Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR. To Reference
Ref 27J Biol Chem. 2007 May 18;282(20):14845-52. Epub 2007 Mar 28.Cellular characterization of a novel focal adhesion kinase inhibitor. To Reference
Ref 28J Med Chem. 2004 Sep 9;47(19):4716-30.N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular efficacy. To Reference
Ref 29Berman 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 30Bioorg Med Chem. 2010 Sep 15;18(18):6785-95. Epub 2010 Jul 25.Novel indolylmaleimide acts as GSK-3beta inhibitor in human neural progenitor cells. To Reference
Ref 31Nat Chem Biol. 2005 Jul;1(2):74-84.Diversity-oriented synthesis: exploring the intersections between chemistry and biology. To Reference



 

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