BGT-002 (326E) is an orally active dual ACLY inhibitor and PPARα agonist. It reduces lipogenesis by inhibiting synthesis and promoting excretion. BGT-002 has demonstrated efficacy in vivo for improving metabolic dysfunction-associated steatohepatitis (MASH) and alleviating hyperlipidemia. It is applicable for research on hypercholesterolemia and MASH.

BGT-002, when administered at concentrations of 3-50 μmol/L for 4 hours, acts as a prodrug of its active form, inhibiting ACLY and consequently reducing CoA-thioester metabolite synthesis and lipid synthesis in mouse primary hepatocytes. At concentrations of 12.5-50 μmol/L over 24 hours, BGT-002 enhances cholesterol efflux in mouse primary hepatocytes by upregulating the ABCG5/8 transport proteins.

BGT-002, administered orally at doses of 15, 30, and 60 mg/kg once daily for 9 weeks, targets ACLY and PPARα to improve MASH in rodent models. At 20 mg/kg, taken orally once daily for 18 weeks, BGT-002 improves MASH and reverses fibrosis in crab-eating macaques. A single oral dose of BGT-002 at 10, 30, and 100 mg/kg significantly suppresses hepatic de novo lipogenesis in fasted-refed mice. When administered at 30 mg/kg either as a single dose or once daily for 7 consecutive days, it enhances cholesterol efflux and reduces hepatic cholesterol in mice on a high-cholesterol diet. Doses of 7.5, 15, 20, and 30 mg/kg, given orally once daily for 2 weeks, improve diet-induced hyperlipidemia in hamsters and spontaneous hyperlipidemia in rhesus monkeys. Lastly, BGT-002 at 15, 30, and 60 mg/kg, administered orally once daily for 24 weeks, ameliorates atherosclerosis in ApoE -/- mice induced by a Western diet (WD).