tcsc3022 CP-640186

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.

IC50 value: 53 nM/61 nM (rat liver ACC1/skeletal muscle ACC2) [1]

Target: acetyl-CoA carboxylase

in vitro: CP-640186, also inhibited both isozymes with IC50s of ~55 nM but was 2–3 times more potent than CP-610431 in inhibiting HepG2 cell fatty acid and TG synthesis. CP-640186 also stimulated fatty acid oxidation in C2C12 cells (ACC2) and in rat epitrochlearis muscle strips with EC50s of 57 nM and 1.3 uM [1].

in vivo: In rats, CP-640186 lowered hepatic, soleus muscle,

quadriceps muscle, and cardiac muscle malonyl-CoA

with ED50s of 55, 6, 15, and 8 mg/kg. Consequently, CP-

640186 inhibited fatty acid synthesis in rats, CD1 mice,

and ob/ob mice with ED50s of 13, 11, and 4 mg/kg, and

stimulated rat whole body fatty acid oxidation with an

ED50 of ~30 mg/kg [1].