PF-05221304 (Clesacostat) is a novel potent, selective, liver-targeted dual acetyl-CoA carboxylase (ACC1/2) inhibitor with IC50 of 13/9 nM (hACC1/2).
PF-05221304 displays no inhibition against a panel of e 5'-diphospho-glucuronosyltransferase (UGT) enzymes at 20 uM, as well as a broad panel of transporters, receptors, ion channels and enzymes, including the hERG channel.
PF-05221304 dose-dependently causes reductions in liver de novo lipogenesis (DNL) with a maximal reduction of 82% (EC50=5.4 nM) at 300 mg/kg (p.o.), weak DNL inhibition in lung and bone marrow.
