Pharmacological inhibitors of glycogen synthase kinase 3.

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Meijer L, Flajolet M, Greengard P

Pharmacological inhibitors of glycogen synthase kinase 3.

Trends Pharmacol Sci. 2004 Sep;25(9):471-80.

PubMed ID
15559249 [ View in PubMed
]
Abstract

Three closely related forms of glycogen synthase kinase 3 (GSK-3alpha, GSK-3beta and GSK-3beta2) have a major role in Wnt and Hedgehog signaling pathways and regulate the cell-division cycle, stem-cell renewal and differentiation, apoptosis, circadian rhythm, transcription and insulin action. A large body of evidence supports speculation that pharmacological inhibitors of GSK-3 could be used to treat several diseases, including Alzheimer's disease and other neurodegenerative diseases, bipolar affective disorder, diabetes, and diseases caused by unicellular parasites that express GSK-3 homologues. The toxicity, associated side-effects and concerns regarding the absorption, distribution, metabolism and excretion of these inhibitors affect their clinical potential. More than 30 inhibitors of GSK-3 have been identified. Seven of these have been co-crystallized with GSK-3beta and all localize within the ATP-binding pocket of the enzyme. GSK-3, as part of a multi-protein complex that contains proteins such as axin, presenilin and beta-catenin, contains many additional target sites for specific modulation of its activity.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AlsterpaulloneCyclin-dependent kinase 1IC 50 (nM)35N/AN/ADetails
AlsterpaulloneGlycogen synthase kinase-3 betaIC 50 (nM)4N/AN/ADetails
AlvocidibCyclin-dependent kinase 1IC 50 (nM)400N/AN/ADetails
Indirubin-3'-monoximeCyclin-dependent kinase 1IC 50 (nM)18N/AN/ADetails
Indirubin-3'-monoximeGlycogen synthase kinase-3 betaIC 50 (nM)22N/AN/ADetails
SB-409513Glycogen synthase kinase-3 betaIC 50 (nM)160N/AN/ADetails
SU9516Cyclin-dependent kinase 1IC 50 (nM)22N/AN/ADetails