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CP-91149

CP-91149

Manufacturer	Selleckchem
Category	Oncology Food Safety Fungicides Metabolism Diabetes Cholesterol & Lipid Metabolism Enzymes Other Fatty Acid Enzymes Inhibitors & Compound Libraries Small Molecules By Organ Lung Cancer
Type	Inhibitors
Specific against	other
Amount	5 mg
Item no.	S2717-5
CASRN	186392-40-5
eClass 6.1	30220300
eClass 9.0	32160605
Available
Administration	Orally
Animal Models	Obese, diabetic male C57BL/6J-Lep(ob/ob) mice and their lean, nondiabetic C57BL/6J- /+ littermates
Cell lines	HSF55 and T98G
Chemical Name	5-chloro-N-((2S, 3R)-4-(dimethylamino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-1H-indole-2-carboxamide
Concentrations	Dissolved in DMSO, final concentrations ca.50 uM
Description	CP-91149 is a selective glycogen phosphorylase (GP) inhibitor with IC50 of 0.13 uM.
Dosages	ca.50 mg/kg
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
IC50	0.13 uM [1], 0.13 uM [1], 0.13 uM [1], 0.13 uM [1], 0.13 uM [1], 0.13 uM [1]
In vitro	CP-91149 displays 200-fold higher inhibitory activity against human liver glycogen phosphorylase a (HLGPa) than caffeine (IC50 = 26 uM). CP-91149 (10-100 uM) inhibits glucagon-stimulated glycogenolysis in isolated rat hepatocytes in a dose-dependent manner, and in primary human hepatocytes with IC50 of ca.2.1 uM. [1] CP-91149 also potently inhibits the activities of human muscle phosphorylase a and b with IC50 of 0.2 uM and ca.0.3 uM, respectively. CP-91149 treatment at 2.5 uM 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. [2] CP-91149 also potently inhibits brain GP with IC50 of 0.5 uM in A549 cells. CP-91149 treatment at 10-30 uM 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. [3] 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. [4]
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. [1] 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. [5]
Incubation Time	72 hours
Kinase Assay	Phosphorylase enzyme assay, Human liver glycogen phosphorylase a (HLGPa, 85 ng) activity is measured in the direction of glycogen synthesis by the release of phosphate from glucose-1-phosphate at 22C in 100 uL of buffer containing 50 mM Hepes (pH 7.2), 100 mM KCl, 2.5 mM EGTA, 2.5 mM MgCl2, 0.5 mM glucose-1-phosphate, and 1 mg/mL glycogen. Phosphate is measured at 620 nm, 20 minutes after the addition of 150 uL of 1 M HCl containing 10 mg/mL ammonium molybdate and 0.38 mg/mL malachite green. Increasing concentrations of CP-91149 are added to the assay in 5 uL of 14% DMSO.
Method	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 488nm for excitation and at 650nm for emission. The cell cycle profile is analyzed using Modifit's Sync Wizard.
Molecular Weight (MW)	399, 87
Picture ChemicalStructure Description	CP-91149 Chemical Structure
Solubility (25C)	DMSO 80 mg/mL, Water <1 mg/mL, Ethanol 2 mg/mL
Storage	2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO

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Amount: 5 mg

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Delivery expected until 5/2/2024