TOFA

TOFA is an inhibitor of acetyl-CoA carboxylase 1 (ACC1) and ACC2 (IC₅₀s = 16.11 and 10.17 µM, respectively) and an agonist of peroxisome proliferator-activated receptor α (PPARα) and PPARδ (EC₅₀s = 2.095 and 0.594 µM, respectively, in cell-based protein-protein interaction assays).¹ It increases the oxygen consumption rate (OCR), proton leak, and spare respiratory capacity in HepG2 hepatoma cells. TOFA reduces body weight and fat mass with no changes in food intake or lean mass in a mouse model of diet-induced obesity (DIO) when administered at 125 mg/kg twice per day for one week, then at 62.5 mg/kg twice per day for three weeks. It reduces fasting blood glucose and insulin, hepatic triglyceride, and circulating lipid levels and improves glucose tolerance in the same model. It increases energy expenditure with no change in body temperature at 200 mg/kg per day. TOFA also reduces hepatic fibrosis and gene expression of inflammatory markers in a mouse model of metabolic dysfunction-associated liver disease (MASLD). In addition, it enhances body weight reduction and glucose control when administered in combination with tirzepatide (Item No. 39748) in DIO mice.

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1. Lee, J.Y., Zhu, C., Boldridge, M.A., et al. A multi-functional oral small molecule targeting energy and lipid metabolism to treat obesity and related metabolic disorders. Sci. Adv. 12(34), eaed3119 (2026).

Lee, J.Y., Zhu, C., Boldridge, M.A., et al. A multi-functional oral small molecule targeting energy and lipid metabolism to treat obesity and related metabolic disorders. Sci. Adv. 12(34), eaed3119 (2026).

Desseaux, V., Koukiekolo, R., Moreau, Y., et al. Mechanism of porcine pancreatic α-amylase: Inhibition of amylose and maltopentaose hydrolysis by various inhibitors. Biologia 57(Suppl 11), 163-170 (2002).