CP 640186

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CP-640186 是一种同工酶非选择性乙酰辅酶A羧化酶 (ACCase) 抑制剂，对大鼠肝脏 ACC1 和大鼠骨骼肌 ACC2 的 IC50 值分别为 53 nM 和 61 nM。

CP-640186 is an isozyme-nonselective Acetyl-CoA carboxylase (ACCase) inhibitor with IC50s of 53 nM and 61 nM for rat liver ACC1 and rat skeletal muscle ACC2 respectively; with improved metabolic stability vs CP-610431.(In Vitro):CP-640186 (20 μM; 48 h) treatment can inhibit H460 cell growth.CP-640186 (0.1 nM-100 μM; 2 h) treatment increases fatty acid metabolism in a concentration-dependent manner in C2C12 cells and muscle strips.CP-640186 (0.62-1.8 μM; 2 h) treatment inhibits fatty acid synthesis and TG synthesis in HepG2 cells.(In Vivo):CP-640186 (oral gavage; 4.6-21 mg/kg; once) demonstrates acute efficacy.CP-640186 (intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once) shows lowe drug exposure in the rat than the ob/ob mouse at equal doses.CP-640186 (oral gavage; 100 mg/kg; once) treatment shows a complete shift from carbohydrate utilization to fatty acid utilization as a source of energy at high exposure level.

CP-640186 (20 μM; 48 h) treatment can inhibit H460 cell growth.CP-640186 (0.1 nM-100 μM; 2 h) treatment increases fatty acid metabolism in a concentration-dependent manner in C2C12 cells and muscle strips. CP-640186 (0.62-1.8 μM; 2 h) treatment inhibits fatty acid synthesis and TG synthesis in HepG2 cells.Cell Proliferation Assay Cell Line:Human fibroblasts and H460 cellsConcentration:20 μM Incubation Time:48 hours Result:Led to a ～30% decrease in cell number compared to vehicle-treated controls.Cell Viability Assay Cell Line:C2C12 cells and muscle strips Concentration:0.1 nM-100 μM Incubation Time:2 hours Result:Stimulated palmitate acid oxidation with an EC50 of 57 nM and a maximal stimulation of 280% in C2C12 cells.Stimulated palmitate acid oxidation with an EC50 of 1.3 μM and a maximal stimulation of 240% in isolated rat epitrochlearis muscle.Cell Viability Assay Cell Line:HepG2 cells Concentration:0.62-1.8 μM Incubation Time:6 hours Result:Inhibited fatty acid synthesis and TG synthesis in HepG2 cells with EC50s of 0.62 μM and 1.8 μM, respecticely.

CP-640186 (oral gavage; 4.6-21 mg/kg; once) demonstrates acute efficacy.CP-640186 (intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once) shows lowe drug exposure in the rat than the ob/ob mouse at equal doses. CP-640186 (oral gavage; 100 mg/kg; once) treatment shows a complete shift from carbohydrate utilization to fatty acid utilization as a source of energy at high exposure level. Animal Model:Male ob/ob miceDosage:4.6-21 mg/kg Administration:Oral gavage; 4.6-21 mg/kg; once Result:Demonstrated acute efficacy for up to 8 h after oral administration, exhibiting ED50 values of 4.6, 9.7, and 21 mg/kg, at 1, 4, and 8 h, respectively, after treatment.Animal Model:Male Sprague-Dawley rats Dosage:Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg Administration:Intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once Result:Showed a plasma half-life of 1.5 h, a bioavailability of 39%, a Clp of 65 ml/min/kg, a Vdss of 5 liters/kg, an oral Tmax of 1.0 h, an oral Cmax of 345 ng/mL, and an oral AUC0-∞ of 960 ng?h/mL.Animal Model:Male ob/ob mice Dosage:Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg Administration:Intravenous injection and oral gavage; Intravenous dose, 5 mg/kg; oral dose, 10 mg/kg; once Result:Showed a plasma half-life of 1.1 h, a bioavailability of 50%, a Clp of 54 ml/min/kg, an oral Tmax of 0.25 h, an oral Cmax of 2177 ng/mL, and an oral AUC0-∞ of 3068 ng?h/mL.Animal Model:Twenty male Sprague-Dawley rats (350-400 g) fasted and then refed a high sucrose diet for 2 days; additional eight rats fasted for 24 h Dosage:100 mg/kg Administration:Oral gavage; 100 mg/kg; once Result:Resulted in time-dependent reductions in RQ (a ratio of CO2 production to O2 consumption) of up to 64%.

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Metabolic Enzyme/Protease

ACC

ACC

Metabolic Disease

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591778-68-6

485.62

C30H35N3O3

>98% (HPLC)

DMSO: 10 mM

C1C[C@H](CN(C1)C2CCN(CC2)C(=O)C3=C4C=CC=CC4=CC5=CC=CC=C53)C(=O)N6CCOCC6

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(-20℃)

With Ice Pack

≥ 2 years