CP-91149

SKU: orb1300754

Description

CP-91149 is a potent and selective glycogen phosphorylase (GP) inhibitor, exhibiting an IC50 of 0.13 μM in a glucose-dependent manner. This small molecule is a valuable research tool for studying glycogen metabolism in type 2 diabetes, utilized in both in vitro enzymatic assays and in vivo metabolic studies.

Research Area

Metabolism Research

Key Properties

• CAS Number: 186392-40-5
• MW: 399.87
• Purity: 99.81% (May vary between batches)
• Formula: C₂₁H₂₂ClN₃O₃
• SMILES: CN(C)C(=O)[C@H](O)[C@H](Cc1ccccc1)NC(=O)c1cc2cc(Cl)ccc2[nH]1
• Target: Phosphorylase,Others
• Solubility: DMSO:40 mg/mL (100.03 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  GP:0.13 μM
• In Vivo:
  Oral administration of CP-91149 to diabetic ob/ob mice at 25-50 mg/kg causes rapid (3 hours) glucose lowering by 100-120 mg/dl without producing hypoglycemia, resulting from inhibition of glycogenolysis in vivo. CP-91149 treatment does not lower glucose levels in normoglycemic, nondiabetic mice. In the non-fasted Goto-Kakizaki (GK) rats, administration of CP-91149 in combination with CS-917 suppresses hepatic glycogen reduction by CS-917 and decreases plasma glucose more than single administration of CS-917.
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• In Vitro:
  CP-91149 displays 200-fold higher inhibitory activity against human liver glycogen phosphorylase a (HLGPa) than caffeine (IC50 = 26 μM). CP-91149 (10-100 μM) inhibits glucagon-stimulated glycogenolysis in isolated rat hepatocytes in a dose-dependent manner, and in primary human hepatocytes with IC50 of ~2.1 μM. CP-91149 also potently inhibits the activities of human muscle phosphorylase a and b with IC50 of 0.2 μM and ~0.3 μM, respectively. CP-91149 treatment at 2.5 μM induces inactivation of phosphorylase and sequential activation of glycogen synthase in hepatocytes, and increases glycogen synthesis by 7-fold at 5 mM glucose and by 2-fold at 20 mM glucose. CP-91149 can partially counteract the effects of phosphorylase overexpression. CP-91149 also potently inhibits brain GP with IC50 of 0.5 μM in A549 cells. CP-91149 treatment at 10-30 μM causes significant glycogen accumulation in A549 and HSF55 cells. CP-91149 treatment increases G1-phase cells with a significant reduction of the S-phase population in HSF55 cells, correlated with increased expression of p21 and p27. 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.
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• Cell Research:
  Cells are exposed to various concentrations of CP-91149 for 72hours. Viability is determined with manual cell counts following staining with trypan blue exclusion assay. Cells are fixed with 70% ethanol. DNA is stained with propidium iodide and the intensity of fluorescence is measured using a Becton-Dickinson flow cytometer at 488 nM for excitation and at 650 nM for emission. The cell cycle profile is analyzed using Modifit's Sync Wizard.(Only for Reference)
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

A549, CP 91149, CP91149, CP-91149, diabetes, inhibit, NSCLC, Inhibitor, Glycogen phosphorylase (GP)

Compound Identifiers

PubChem CID

9843900