ACC1 inhibitor Compound 1 is a potent, highly selective, oral ACC1 inhibitor with IC50 of 0.58 nM (hACC1), no effect on hACC2 (IC50>10 uM).
ACC1 inhibitor Compound 1 inhibits mouse ACC1 and ACC2 with IC50 values of 1.9 nM and > 10,000 nM, respectively; ACC1 inhibitor Compound 1 decreased the M-CoA content in in HepG2 cells with IC50 of 16.0 nM, inhibited [14C] acetate incorporation into fatty acids with IC50 of 12.7 nM.
ACC1 inhibitor Compound 1 suppressed hepatic M-CoA content in C57BL/6J mice, the IC50 of hepatic M-CoA reduction was 1.88 μg/mL (0.90 mg) of plasma concentration in C57BL/6J mice.
ACC1 inhibitor Compound 1 improves hepatic steatosis and fibrosis in WD-fed MC4R KO mice, Compound 1 treatment markedly decreased plasma AST, ALT, and TC levels in a dose-dependent manner.
ACC1 inhibitor Compound 1 improves hepatic steatosis and hepatic fibrosis in a preclinical nonalcoholic steatohepatitis model.