Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase involved in cell differentiation, cellular growth and proliferation, apoptosis, and inflammation. There are two isoforms of GSK-3, GSK-3α and GSK-3β. 1-Azakenpaullone is a potent inhibitor of GSK-3β with an IC50 value of 18 nM. In contrast, the IC50 values of 1-Azakenpaullone against CDK1/cycline B and CDK5/p25 were 2.0 and 4.2 μM, respectively[3]. 1-Azakenpaullone at the concentrations of 5, 10, and 15 μM significantly promoted DNA synthesis in human pancreatic islets above the levels at 8 mM glucose. Exposure of human pancreatic islets to 8 mM glucose and 15 μM 1-Azakenpaullone significantly reduced cells in G0/G1 phase and increased cells in S phase. Combined treatment of human islets with 8 mM glucose and 5 μM 1-Azakenpaullone significantly increased Ki-67+/insulin+ cells as compared with basal glucose[4]. After 2-week administration of 1-Azakenpaullone, a significant reduction in the levels of phosphorylated Akt GSK-3β, and cyclin D1 was observed in the islets of c-KitW/+ mice when compared to c-Kit+/+ mice[5].
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