Journal of Medicinal Chemistry · 2004 · 102 citations · 19 references
MedicineMedicinal ChemistryPharmacologyBiochemical PharmacologyDrug DiscoveryMolecular PharmacologyDiabetes MellitusDiabetes Mellitus BiochemistryEnzyme InhibitionGlycemic ControlOral Antidiabetic AgentsAntidiabetic ActivityAntidiabetic Drug TherapyGlycogen Synthase Kinase 3 SignalingIn Vivo StudiesInsulin Receptor SignalingInsulin ReceptorsType 2 Diabetes PharmacotherapyType 2 Diabetes Treatment
Glycogen synthase kinase-3 (GSK3) is involved in signaling from the insulin receptor. Inhibitors of GSK3 are expected to effect lowering of plasma glucose similar to insulin, making GSK3 an attractive target for the treatment of type 2 diabetes. Herein we report the discovery of a series of potent and selective GSK3 inhibitors. Compounds 7-12 show oral activity in an in vivo model of type II diabetes, and 9 and 12 have desirable PK properties.
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Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Darren A.E. Cross, Dario R. Alessi, Philip Cohen et al. · Nature · 1995 · 5.2K citations