Target Validation Information
TTD ID T70977
Target Name Glycogen synthase kinase-3 beta (GSK-3B)
Type of Target
Clinical trial
Drug Potency against Target Enzastaurin Drug Info IC50 = 30 nM [18]
Drug Info IC50 = 16600 nM [7]
(E)-N-(6-(prop-1-enyl)-1H-indazol-3-yl)butyramide Drug Info IC50 = 2459 nM [14]
12,13-DEHYDRO-8-O-ACETYLMANZAMINE A Drug Info IC50 = 4800 nM [7]
12,13-DEHYDROMANZAMINE A Drug Info IC50 = 5400 nM [7]
3-(6-(phenylamino)-9H-purin-8-yl)benzonitrile Drug Info IC50 = 26 nM [16]
3-phenyl-4-(phenylamino)-1H-pyrrole-2,5-dione Drug Info IC50 = 520 nM [9]
4-(5-bromo-1H-indol-3-yl)pyrimidin-2-amine Drug Info IC50 = 2000 nM [11]
8-O-(4-chlorobenzenesulfonyl)manzamine F Drug Info IC50 = 7200 nM [7]
9-N-ETHYL-8-ETHOXY-MANZAMINE A Drug Info IC50 = 10400 nM [7]
AR-A014418 Drug Info IC50 = 100 nM [11]
AS-601245 Drug Info IC50 = 40 nM [8]
AZAKENPAULLONE Drug Info IC50 = 18 nM [2]
CT-98024 Drug Info IC50 = 0.56 nM [13]
ELLAGIC ACID Drug Info IC50 = 7500 nM [6]
KENPAULLONE Drug Info IC50 = 23 nM [2]
LEUCETTAMINE B Drug Info IC50 = 15000 nM [12]
MANZAMINE A Drug Info IC50 = 10200 nM [10]
N,8-diphenyl-9H-purin-6-amine Drug Info IC50 = 16 nM [16]
N-(6-(2-chlorophenyl)-1H-indazol-3-yl)butyramide Drug Info IC50 = 1353 nM [14]
N-(6-(3-hydroxyphenyl)-1H-indazol-3-yl)butyramide Drug Info IC50 = 94 nM [14]
N-(6-(4-aminophenyl)-1H-indazol-3-yl)butyramide Drug Info IC50 = 76 nM [14]
N-(6-(4-fluorophenyl)-1H-indazol-3-yl)butyramide Drug Info IC50 = 5008 nM [14]
N-(6-(4-hydroxyphenyl)-1H-indazol-3-yl)butyramide Drug Info IC50 = 44 nM [14]
N-(6-(furan-3-yl)-1H-indazol-3-yl)butyramide Drug Info IC50 = 260 nM [14]
N-(6-(pyridin-3-yl)-1H-indazol-3-yl)butyramide Drug Info IC50 = 5900 nM [15]
N-(6-(pyridin-4-yl)-1H-indazol-3-yl)butyramide Drug Info IC50 = 661 nM [14]
N-(6-(thiophen-3-yl)-1H-indazol-3-yl)butyramide Drug Info IC50 = 935 nM [14]
N-(6-(trifluoromethyl)-1H-indazol-3-yl)butyramide Drug Info IC50 = 195 nM [14]
N-(6-benzyl-1H-indazol-3-yl)butyramide Drug Info IC50 = 4140 nM [14]
N-(6-bromo-1H-indazol-3-yl)butyramide Drug Info IC50 = 198 nM [14]
N-(6-chloro-1H-indazol-3-yl)butyramide Drug Info IC50 = 354 nM [14]
N-(6-chloro-5-p-tolyl-1H-indazol-3-yl)butyramide Drug Info IC50 = 14000 nM [14]
N-(6-chloro-5-phenyl-1H-indazol-3-yl)butyramide Drug Info IC50 = 80 nM [15]
N-(6-phenethyl-1H-indazol-3-yl)butyramide Drug Info IC50 = 8525 nM [14]
N-(6-phenyl-1H-indazol-3-yl)butyramide Drug Info IC50 = 390 nM [15]
N-(8-(3-cyanophenyl)-9H-purin-6-yl)pentanamide Drug Info IC50 = 1220 nM [16]
NU-6102 Drug Info IC50 = 40 nM [4]
PAULLONE Drug Info IC50 = 100 nM [13]
PYRAZOLOPYRIDAZINE 1 Drug Info Ki = 10 nM [3]
PYRAZOLOPYRIDAZINE 2 Drug Info Ki = 10 nM [3]
RO-320432 Drug Info IC50 = 20 nM [13]
Ro31-8220 Drug Info IC50 = 38 nM [1]
Thieno analogue of kenpaullone Drug Info IC50 = 120 nM [2]
TWS-119 Drug Info IC50 = 30 nM [5]
Action against Disease Model SB216763 Drug Info Pharmacological GSK-3 inhibitors such as the maleimide SB216763 or the aminopyrazole GSK inhibitor XIII inhibited AR-dependent reporter gene activity and AR expression in vitro.Analysis of androgen-induced nuclear translocation of the AR was performed in PC3 cells transfected with pAR-t1EosFP coding for EosAR, a green fluorescent AR fusion protein. When grown in presence ofandrogens, EosAR was predominantly nuclear. Incubation with SB216763 before and after androgen treatment almost completely reduced nuclear EosAR. In contrast, the thiazole-containing urea compound AR-A014418 increased rather than decreased AR-expression/function. Although not all GSK inhibitors affected AR-stability/function, our observations suggest a potential new therapeutic application for some of these compounds in prostate cancer [17]
References
REF 1 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
REF 2 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
REF 3 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 effi... J Med Chem. 2004 Sep 9;47(19):4716-30.
REF 4 Triazolo[1,5-a]pyrimidines as novel CDK2 inhibitors: protein structure-guided design and SAR. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1353-7.
REF 5 Diversity-oriented synthesis: exploring the intersections between chemistry and biology. Nat Chem Biol. 2005 Jul;1(2):74-84.
REF 6 Identification of ellagic acid as potent inhibitor of protein kinase CK2: a successful example of a virtual screening application. J Med Chem. 2006 Apr 20;49(8):2363-6.
REF 7 Glycogen synthase kinase-3 (GSK-3) inhibitory activity and structure-activity relationship (SAR) studies of the manzamine alkaloids. Potential for ... J Nat Prod. 2007 Sep;70(9):1397-405.
REF 8 The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
REF 9 Novel GSK-3beta inhibitors from sequential virtual screening. Bioorg Med Chem. 2008 Jan 15;16(2):636-43.
REF 10 2-N-Methyl modifications and SAR studies of manzamine A. Bioorg Med Chem. 2008 Jul 15;16(14):6702-6.
REF 11 Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
REF 12 Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid leucettamine B as kinase inhibitors. Eur J Med Chem. 2010 Feb;45(2):805-10.
REF 13 Discovery of potent and bioavailable GSK-3beta inhibitors. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1693-6.
REF 14 Rational design of potent GSK3beta inhibitors with selectivity for Cdk1 and Cdk2. Bioorg Med Chem Lett. 2010 Mar 15;20(6):1985-9.
REF 15 Design of potent and selective GSK3beta inhibitors with acceptable safety profile and pharmacokinetics. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2344-9.
REF 16 Novel 8-arylated purines as inhibitors of glycogen synthase kinase. Eur J Med Chem. 2010 Aug;45(8):3389-93.
REF 17 Inhibition of glycogen synthase kinase-3 in androgen-responsive prostate cancer cell lines: are GSK inhibitors therapeutically useful Neoplasia. 2008 Jun;10(6):624-34.
REF 18 Small molecule inhibitors of PKCTheta as potential antiinflammatory therapeutics. Curr Top Med Chem. 2009;9(7):640-54.

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