ND-646

**ND-646** is a potent, selective, and orally bioavailable small molecule inhibitor targeting acetyl-CoA carboxylase isoforms ACC1 and ACC2. ND-646 functions as an allosteric inhibitor, binding at the dimerization site of the biotin carboxylase (BC) domain, thereby preventing dimerization and enzymatic activity essential for de novo fatty acid synthesis in cells. By inhibiting both ACC1 and ACC2, ND-646 disrupts the production of fatty acids required for tumor cell growth and viability, particularly in non-small cell lung cancer (NSCLC) models. Preclinical studies demonstrate ND-646's efficacy in suppressing tumor growth both as a monotherapy and in combination with standard chemotherapy (carboplatin), with the combination showing even greater anti-tumor activity. ND-646 administration leads to reduced proliferation, increased apoptosis associated with ER stress, depletion of cellular and plasma fatty acids, and marked tumor regression in multiple NSCLC models. The compound offers a promising therapeutic avenue in oncology by exploiting tumor metabolic vulnerabilities.