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Glycogen Synthase Kinase (GSK) Inhibitor
No.172(January 2017)
Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase and was first isolated from rabbit skeletal muscle.1) There are two isoforms of mammalian GSK-3, including GSK-3α and GSK-3β, which are encoding by separate genes (GSK3A, GSK3B).2) GSK-3 is associated with various signaling pathways including the wnt/β-catenin pathway.3)
A large number of GSK-3 inhibitors have been reported and classified into two types, ATP-competitive and non-ATP-competitive inhibitors.4) TDZD-8 (Thiadiazolidine-8, 1) is a non-ATP-competitive inhibitor of GSK-3β (Study I in the Table).5) Interestingly, in the study using PKC isoforms, it is shown that PKCβ 1, PKCδ, and PKCι are also inhibited by 1 (Study II in the Table).6)
References
- 1)Glycogen synthase kinase-3 from rabbit skeletal muscle, separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase
- 2)Molecular cloning and expression of glycogen synthase kinase-3/Factor A
- 3)GSK-3: Tricks of the trade for a multi-tasking kinase
- 4)Glycogen synthase kinase-3 (GSK-3)-targeted therapy and imaging
- 5)First non-ATP competitive glycogen synthase kinase 3β (GSK-3β) inhibitors: Thiadiazolidinones (TDZD) as potential drugs for the treatment of Alzheimer’s disease
- 6)Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1,2,4-thiadiazolidine, 3,5 dione (TDZD-8)
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