Pharmacological inhibitors of glycogen synthase kinase 3.
Article Details
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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
Drug Target Property Measurement pH Temperature (°C) Alsterpaullone Cyclin-dependent kinase 1 IC 50 (nM) 35 N/A N/A Details Alsterpaullone Glycogen synthase kinase-3 beta IC 50 (nM) 4 N/A N/A Details Alvocidib Cyclin-dependent kinase 1 IC 50 (nM) 400 N/A N/A Details Indirubin-3'-monoxime Cyclin-dependent kinase 1 IC 50 (nM) 18 N/A N/A Details Indirubin-3'-monoxime Glycogen synthase kinase-3 beta IC 50 (nM) 22 N/A N/A Details SB-409513 Glycogen synthase kinase-3 beta IC 50 (nM) 160 N/A N/A Details SU9516 Cyclin-dependent kinase 1 IC 50 (nM) 22 N/A N/A Details