CP-640186 (hydrochloride)

CP-640186 hydrochloride is an orally active and cell-permeable Acetyl-CoA carboxylase (ACC) inhibitor with IC₅₀s 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^[1][2]. IC50 & Target: IC50: 53 nM (rat liver ACC1) and 61 nM (rat skeletal muscle ACC2)^[1] In Vitro: CP-640186 (20 µM; 48 h) treatment can inhibit H460 cell growth^[3].
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^[1].
CP-640186 (0.62-1.8 µM; 2 h) treatment inhibits fatty acid synthesis and TG synthesis in HepG2 cells^[1]. In Vivo: CP-640186 (oral gavage; 4.6-21 mg/kg; once) demonstrates acute efficacy^[1].
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^[1].
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^[1].