CP-91149

CP-91149 is a selective small molecule inhibitor of glycogen phosphorylase (GP), specifically targeting the human liver isoform (glycogen phosphorylase a). It acts by binding to the inhibitor site of GP, with an IC50 of approximately 0.13 µM in the presence of glucose. The compound is significantly less potent in the absence of glucose. By inhibiting glycogen phosphorylase, CP-91149 suppresses hepatic glycogenolysis and promotes glycogen resynthesis without causing overaccumulation. In preclinical studies, oral administration in diabetic ob/ob mice led to rapid and significant reductions in blood glucose levels without inducing hypoglycemia or affecting normoglycemic animals. Mechanistically, inhibition of GP by CP‑91149 also results in activation and translocation of glycogen synthase—mimicking insulin-stimulated pathways—and can induce G1 cell cycle arrest via cyclin E-CDK2 inhibition in some cell types. Developed as a potential antidiabetic agent for type 2 diabetes mellitus, it has also been studied for effects on cancer cell metabolism[1][4][5][7][8][9].

Other names

5-Chloro-N-[(1S,2R)-3-(dimethylamino)-2-hydroxy-3-oxo-1-(phenylmethyl)propyl]-1H-indole-2-carboxamide