CP-640186 hydrochloride is an orally active and cell-permeable Acetyl-CoA carboxylase ( ACC ) inhibitor with IC 50 s of 53 nM and 61 nM for rat liver ACC1 and rat skeletal muscle ACC2 respectively. Acetyl-CoA carboxylase (ACC) is a key enzyme of fatty acid metabolism that enables the synthesis of malonyl-CoA. CP-640186 hydrochloride can also stimulate muscle fatty acid oxidation

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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: Human fibroblasts and H460 cells Concentration: 20 µM Incubation Time: 48 hours Result: Led to a ∼30% decrease in cell number compared to vehicle-treated controls. Cell Viability AssayCell Line: C2C12 cells and muscle strips Concentration: 0.1 nM-100 µM Incubation Time: 2 hours Result: Stimulated palmitate acid oxidation with an EC 50 of 57 nM and a maximal stimulation of 280% in C2C12 cells. Stimulated palmitate acid oxidation with an EC 50 of 1.3 μM and a maximal stimulation of 240% in isolated rat epitrochlearis muscle. Cell Viability AssayCell 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 EC 50 s of 0.62 μM and 1.8 μM, respecticely.

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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male ob/ob mice Dosage: 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 ED 50 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 Cl p of 65 ml/min/kg, a V dss of 5 liters/kg, an oral T max of 1.0 h, an oral C max of 345 ng/mL, and an oral AUC 0-∞ 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 Cl p of 54 ml/min/kg, an oral T max of 0.25 h, an oral C max of 2177 ng/mL, and an oral AUC 0-∞ 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 CO 2 production to O 2 consumption) of up to 64%.

IC50& Target:IC50: 53 nM (rat liver ACC1) and 61 nM (rat skeletal muscle ACC2)

规格

别名

CP-640186 盐酸盐

规格或纯度

10mM in DMSO

英文名称

CP-640186 hydrochloride

生化机理

CP-640186 盐酸盐是一种具有口服活性和细胞渗透性的乙酰-CoA 羧化酶（ACC）抑制剂，对大鼠肝脏 ACC1 和大鼠骨骼肌 ACC2 的 IC 50 s 分别为 53 nM 和 61 nM。乙酰-CoA羧化酶（ACC）是脂肪分解过程中的一种关键酶。

储存条件

干燥,-80℃储存

运输条件

特低温运输

作用类型

抑制剂

名称和识别符

分子类型

小分子

Isomeric SMILES

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

PubChem CID

23589188

分子量

522.08

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