CP 91,149 is an inhibitor of human liver glycogen phosphorylase a (LGPa), muscle glycogen phosphorylase a (MGPa), and MGPb (IC50s = 0.13, 0.2, and 0.3 μM, 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 μM) and increases glycogen synthesis in rat hepatocytes at a concentration of 2.5 μM in the presence of 5 mM glucose. CP 91,149 inhibits brain GP (IC50 = 0.5 μM) and, at a concentration of 30 μM, 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.
