Cat. No. Name Size Price Add Cart
KI0564CP-911495 mg$112
CP-9114910 mg$176
CP-91149100 mg$592

Chemical Characteristic

Product NameCP-91149
CAS No.186392-40-5
Molecular Weight 399.87
FormulaC21H22ClN3O3
Chemical Name5-Chloro-N-[(1S,2R)-3-(dimethylamino)-2-hydroxy-3-oxo-1-(phenylmethyl)propyl]-1H-indole-2-carboxamide
Smiles[nH]1c(cc2cc(ccc12)Cl)C(=O)NC(Cc1ccccc1)[C@@H](C(=O)N(C)C)O
Chemical Structure

Biological activities

CP-91149 is a glycogen phosphorylase inhibitor. The IC50 of CP-91149 is 0.13 μM against human liver glycogen phosphorylase a (HLGPa). CP-91149 inhibits recombinant human liver glycogen phosphorylase a (rHLGPa) with an IC50 of 110 nM.[1] CP-91149 treatment decreases muscle glycogen phosphorylase (GP) activity by converting the phosphorylated AMP-independent a form into the dephosphorylated AMP-dependent b form and inhibiting GP a activity and AMP-mediated GP b activation. CP-91149 impairs the glycogenolysis induced by glucose deprivation. CP-91149 also promotes the dephosphorylation and activation of GS (glycogen synthase) in non-engineered or GP-overexpressing cultured human muscle cells, but exclusively in glucose-deprived cells. CP-91149 also promotes the dephosphorylation and activation of GS (glycogen synthase) in non-engineered or GP-overexpressing cultured human muscle cells, but exclusively in glucose-deprived cells.[2] CP-91149 inactivates phosphorylase with sequential activation of glycogen synthase. CP-91149 increases glycogen synthesis by 7-fold at 5 mm glucose and by 2-fold at 20 mm glucose with a decrease in the concentration of glucose causing half-maximal rate (S(0.5)) from 26 to 19 mm. Low levels of phosphorylase expression inhibits glycogen synthesis by 50%, with little further inhibition at higher enzyme expression, and causes inactivation of glycogen synthase that is reversed by CP-91149.[3] CP-91149 induces inactivation (dephosphorylation) of phosphorylase in the absence of hormones and partially counteracted the phosphorylation caused by glucagon.[4] Dephosphorylation of phosphorylase a with CP-91149 that causes dephosphorylation of phosphorylase a, to determine the relative contributions of inactivation of GSK-3 and dephosphorylation of phosphorylase a as alternative pathways in the stimulation of glycogen synthesis by insulin in hepatocytes.[5] In ob/ob mice pretreated with 14C-glucose to label liver glycogen, CP-91149 administration reduces 14C-glycogen breakdown, confirming that glucose lowering results from inhibition of glycogenolysis in vivo.[1]

Protocols

CP-91149 is dissolved in either 0.25% (wt/vol) methyl cellulose in water or 0.1% Pluronic P105 Block Copolymer Surfactant in 0.1% saline.[1]

References

[1] Martin WH, et al. Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo. Proc Natl Acad Sci U S A. 1998, 95(4): 1776-1781.
[2] Ler?n C, et al. Regulation of glycogen metabolism in cultured human muscles by the glycogen phosphorylase inhibitor CP-91149. Biochem J. 2004, 378(Pt 3): 1073-1077.
[3] Aiston S, et al. Hepatic glycogen synthesis is highly sensitive to phosphorylase activity: evidence from metabolic control analysis. J Biol Chem. 2001, 276(26): 23858-23866.
[4] Latsis T, et al. Diverse effects of two allosteric inhibitors on the phosphorylation state of glycogen phosphorylase in hepatocytes. Biochem J. 2002, 368(Pt 1): 309-316.
[5] Aiston S, et al. Inactivation of phosphorylase is a major component of the mechanism by which insulin stimulates hepatic glycogen synthesis. Eur J Biochem. 2003, 270(13): 2773-2781.

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