MK-4074

MK-4074 is a liver-specific, orally administered small molecule inhibitor of acetyl-CoA carboxylase isoforms ACC1 and ACC2, with an IC50 of approximately 3 nM for both targets. It was developed as a potential treatment for nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), diabetes mellitus, and fatty liver. MK-4074 achieves high specificity for the liver due to its uptake by organic anion transport proteins (OATP) present in hepatocytes and its excretion via the MRP2 efflux transporter. By inhibiting ACC1/ACC2, MK-4074 reduces hepatic de novo lipogenesis, lowers malonyl-CoA levels, increases fatty acid oxidation and ketone body production, and decreases hepatic triglyceride accumulation. Preclinical studies demonstrated significant reductions in hepatic lipid content and improvements in metabolic parameters relevant to NAFLD/NASH models[1][3][5][6][7].