ND-630 is an allosteric inhibitor of acetyl-CoA carboxylase (ACC) dimerization that inhibits ACC1 and ACC2 activity (IC50s = 2.1 and 6.1 nM, respectively, for the human enzymes). It is selective for ACC over 101 enzymes, receptors, growth factors, transporters, and ion channels up to a concentration of 10 μM. ND-630 prevents dimerization of ACC by interacting within the phosphopeptide-acceptor and dimerization site. It reduces fatty acid synthesis (EC50s = 66 and 9 nM in 10% FBS and serum-free media, respectively) and increases fatty acid oxidation in HepG2 cells. ND-630 reduces hepatic steatosis in a rat model of diet-induced obesity and in Zucker diabetic rats. It also improves insulin secretion stimulated by glucose and reduces hemoglobin A1c levels by 0.9% in Zucker diabetic rats.
