CP-91149

- Overview
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    Background
    
    CP-91149 is a selective inhibitor of glycogen phosphorylase (GP) with an IC50 value of 0.13 μM.
    Glycogen phosphorylase is a phosphorylase enzymes that can catalize phosphorolytic cleavage of the glycosidic linkages of glycogen by releasing glucose-1-phosphate from the terminal alpha-1, 4-glycosidic bond. It controls the rate-limiting step in glycogenolysis in the cells.
    In vitro, CP-91149 treatment suppressed glycogenolysis stimulated by glucagon in in primary human hepatocytes and isolated rat hepatocytes with IC50 value of 2.1 μM and 10–100 μM, respectively 1. Inhibition of phosphorylase a by CP-91149 resulted in activation of glycogen synthase and translocation of the protein from a soluble to a particulate fraction, which mimicked the insulin- stimulated glycogen synthesis 2.
    In vivo, treatment of CP-91149 on diabetic ob/ob mice at a dosage of 25–50 mg/kg was shown to lead to a rapid glucose lowering but did not change glucose levels in normoglycemic, nondiabetic mice 1.
    
    1. Martin WH, Hoover DJ, Armento SJ, et al. Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. Proceedings of the National Academy of Sciences of the United States of America. 1998;95(4):1776-1781.
    2. Aiston S, Coghlan MP, Agius L. Inactivation of phosphorylase is a major component of the mechanism by which insulin stimulates hepatic glycogen synthesis. European journal of biochemistry / FEBS. 2003;270(13):2773-2781.
- Properties
  - Alternative Name
    
    5-chloro-N-[(2S,3R)-4-(dimethylamino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl]-1H-indole-2-carboxamide
    
    CAS Number
    
    186392-40-5
    
    Molecular Formula
    
    C21H22ClN3O3
    
    Molecular Weight
    
    399.87
    
    Purity
    
    98.00%
    
    Solubility
    
    insoluble in H2O; ≥16.4 mg/mL in DMSO; ≥3.17 mg/mL in EtOH with ultrasonic
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Barot S, Abo-Ali EM, et al. "Inhibition of glycogen catabolism induces intrinsic apoptosis and augments multikinase inhibitors in hepatocellular carcinoma cells." Exp Cell Res. 2019 Aug 15;381(2):288-300. PMID:31128107

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CP-91149

Background

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