CP-91149

Description: CP 91, 149 is a novel, potent and selective inhibitor of human liver glycogen phosphorylase a (LGPa) with IC50 of 0.13 uM in the presence of glucose, 5- to 10-fold less potent in the absence of glucose. It also inhibits muscle glycogen phosphorylase a (MGPa), and MGPb (IC50s = 0.13, 0.2, and 0.3 uM, respectively, in the presence of glucose. CP 91, 149 is 5- to 10-fold less potent in the absence of glucose. In vitro, it inhibits glucagon-stimulated glycogenolysis in primary human hepatocytes (IC50 = 2.1 uM) and increases glycogen synthesis in rat hepatocytes at a concentration of 2.5 uM in the presence of 5 mM glucose. CP 91, 149 inhibits brain GP (IC50 = 0.5 uM) and, at a concentration of 30 uM, inhibits glycogen accumulation and proliferation of A549 non-small cell lung carcinoma (NSCLC) cells that express endogenous brain GP. In vivo, CP 91, 149 (25 mg/kg, p.o.) lowers the plasma glucose level in diabetic ob/ob mice within 3 hours of administration without producing hypoglycemia, but has no effect on normoglycemic, non-diabetic mice. CP-91149 is a selective glycogen phosphorylase (GP) inhibitor with IC50 of 0.13 uM in the presence of glucose, 5- to 10-fold less potent in the absence of glucose.

References: European journal of biochemistry / FEBS. 2003; 270(13):2773-2781; Proceedings of the National Academy of Sciences of the United States of America. 1998; 95(4):1776-1781.