Cayman PF-05221304

PF-05221304 is an inhibitor of acetyl-CoA carboxylase 1 (ACC1) and ACC2 (IC₅₀s = 12.4 and 8.7 nM, respectively).¹ It inhibits de novo lipid synthesis (IC₅₀ = 61 nM) and increases fatty acid oxidation in primary human hepatocytes. PF-05221304 reduces the accumulation of triglycerides composed of de novo-derived fatty acids but not dietary essential fatty acids in primary human hepatocytes. In vivo, PF-05221304 (10 and 100 mg/kg) reduces hepatic malonyl-CoA production and de novo lipogenesis in rats. It reduces hepatic fibrosis, alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, and triglyceride accumulation in a rat model of non-alcoholic steatohepatitis (NASH) induced by a choline-deficient and high-fat diet (CDAHFD).

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