TVB-3664

TVB-3664 is a potent, selective, orally active, and reversible small molecule inhibitor of fatty acid synthase (FASN), the key enzyme in the de novo lipogenesis pathway responsible for converting dietary sugars into palmitate. It exhibits high bioavailability and strong inhibitory activity with IC50 values of 0.018 μM for human and 0.012 μM for mouse FASN. Preclinical studies have shown that TVB-3664 significantly reduces tubulin palmitoylation and mRNA expression, disrupts microtubule organization in tumor cells, and enhances anti-tumor activity when combined with taxanes or BH3 mimetics such as navitoclax or venetoclax. In metabolic disease models, particularly metabolic dysfunction-associated steatohepatitis (MASH), TVB-3664 improves metabolic, biochemical, and histopathological parameters including NAFLD Activity Score (NAS). It has also demonstrated synergistic effects when combined with thyroid hormone receptor beta agonists like resmetirom in preclinical MASH models[1][2][3][5][6][8].