CP-610431

CP-610431 is a reversible, ATP-uncompetitive, isozyme-nonselective acetyl-CoA carboxylase (ACC) inhibitor. CP-610431 inhibits ACC1 and ACC2 with IC₅₀s of ~50 nM. CP-610431 can be used for the research of metabolic syndrome^[1]. In Vitro: CP-610431 is the active R-enantiomer of CP-497485. CP-610431 is more potent than the racemate CP-497485 in inhibiting rat ACC1 (IC₅₀=35.7 nM) and ACC2 (IC₅₀=55 nM), whereas the?S-enantiomer, CP-610432, does not substantially inhibit either ACC isoform at concentrations of up to 3 μM. CP-610431 is more potent than CP-497485 in inhibiting HepG2 cell fatty acid and triglyceride (TG) synthesis and in inhibiting TG and apoB secretion^[1].
CP-610431 inhibits fatty acid synthesis, triglyceride synthesis, TG secretion, and apolipoprotein B secretion in HepG2 cells (ACC1) with EC₅₀s of 1.6, 1.8, 3.0, and 5.7 μM, without affecting either cholesterol synthesis or apolipoprotein CIII secretion^[1].
CP-610431 inhibits both liver and skeletal muscle ACC activity from all three species with essentially equal potency (rat, 36?versus?55 nM; mouse, 50?versus?63 nM; cynomolgus macaque, 70?versus?26 nM) ^[1].
CP-610431 inhibits mouse primary hepatocyte fatty acid and TG synthesis with IC₅₀?values of 0.11 and 1.2 μM?and inhibits TG secretion with an IC₅₀?of 10 μM^[1]. In Vivo: CP-610431 inhibits fatty acid synthesis in CD1 mice and ob/ob mice within 1 h after dose with ED₅₀s of 22 and 4 mg/kg,?respectively^[1].