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CP-91149 is a human liver glycogen phosphorylase α (HLGPα) inhibitor with an IC50 of 0.13 μM in the presence of 7.5 mM glucose. CP-91149 suppressed glucagon-triggered glycogenolysis in isolated rat hepatocytes and in primary human hepatocytes. In vivo, oral injection of CP-91149 to diabetic ob/ob mice at 25–50 mg/kg led in rapid (3 h) glucose lowering by 100–120 mg/dl without producing hypoglycemia. In addition, upon treatment with CP-91149, A549 non-small cell lung carcinoma (NSCLC) cells accumulated glycogen with associated growth retardation. Treated normal skin fibroblasts also accumulated glycogen with G1-cell cycle arrest that was associated with inhibition of cyclin E-CDK2 activity. Overall, cells expressing high levels of brain GP were growth prevented by CP-91149 associating with glycogen accumulation whereas cells expressing low levels of brain GP were not affected by the agent.
| Cell Experiment | |
|---|---|
| Cell lines | HSF55 and T98G |
| Preparation method | Exposing cells to various concentrations of CP-91149 for 72hours. Determining viability with manual cell counts following staining with trypan blue exclusion assay. Fixing cells with 70% ethanol. Staining DNA with propidium iodide and the intensity of fluorescence is measured using a Becton-Dickinson flow cytometer at 488nm for excitation and at 650nm for emission. Using Modifit's Sync Wizard is analyze the cell cycle profile . |
| Concentrations | Dissolved in DMSO, final concentrations ~50 μM |
| Incubation time | 72 hours |
| Animal Experiment | |
|---|---|
| Animal models | Obese, diabetic male C57BL/6J-Lep(ob/ob) mice and their lean, nondiabetic C57BL/6J-/+ littermates |
| Formulation | Formulated in vehicle consisting of either 0.25% (wt/vol) methyl cellulose in water or 0.1% Pluronic P105 Block Copolymer Surfactant in 0.1% saline |
| Dosages | ~50 mg/kg |
| Administration | Orally |
| Molecular Weight | 399.87 |
| Formula | C21H22ClN3O3 |
| CAS Number | 186392-40-5 |
| Solubility (25°C) | DMSO 70 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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