ND-654

ND-654 is a liver-selective, small-molecule allosteric inhibitor of acetyl-CoA carboxylase 1 (ACC1) and acetyl-CoA carboxylase 2 (ACC2) developed by Nimbus Therapeutics. It is designed to mimic the natural inhibitory effect of AMPK-mediated phosphorylation on ACC, the rate-limiting enzyme in de novo lipogenesis (DNL). By inhibiting ACC, ND-654 reduces the synthesis of fatty acids, which are essential for tumor cell proliferation and survival in hepatocellular carcinoma (HCC). Additionally, the reduction in hepatic fat accumulation makes it a candidate for metabolic liver diseases such as non-alcoholic steatohepatitis (NASH) and non-alcoholic fatty liver disease (NAFLD). ND-654 is specifically engineered for high liver-to-systemic exposure to maximize therapeutic efficacy in the liver while minimizing potential systemic side effects.