ND-630

ND-630 (NDI 010976) is a highly specific, reversible inhibitor of ACC1 (IC50 = 2 nM) and ACC2 (IC50 = 6 nM). ND-630 interacts within the ACC phosphopeptide acceptor and dimerization site to prevent dimerization of ACC. Because the dimerization site is not conserved among other mammalian carboxylases, ND-630 lacks the ability to inhibit other mechanistically-related enzymes. In rats with diet-induced obesity, ND-630 reduced hepatic steatosis, improved insulin sensitivity, and reduced weight gain, suggesting ACC inhibition may be useful in treating metabolic disorders, including type 2 diabetes mellitus, and fatty liver disease.