Turofexorate isopropyl (WAY-362450) is a potent, selective, and orally bioavailable agonist of the farnesoid X receptor (FXR) with an EC50 of 4 nM[1].
Turofexorate isopropyl 动物研究
Animal study
Turofexorate isopropyl (WAY-362450) also demonstrates potent cholesterol and triglyceride-lowering effects in LDLR-/- mice and shows antiatherogenic activity by reducing aortic arch lesions. Oral administration of WAY-362450 in these mice leads to significant lipid reductions, and chronic dosing in an atherosclerosis model significantly diminishes aortic arch lesions. Administered to rats at 3 mg/kg (orally and intravenously), WAY-362450 displays good oral bioavailability (38%), a lengthy half-life of 25 hours, a modest volume of distribution, and low clearance (3.3 L/kg, about 10% of hepatic blood flow). Further pharmacokinetic data from studies in mice and higher species have been gathered and are to be published separately[1].In rat models, Turofexorate isopropyl elevates HDL cholesterol levels, whereas in hamsters, it reduces levels similarly to those observed in mice[2].In wild-type mice treated with 30 mg/kg of Turofexorate isopropyl, there is an induction of SHP expression, an effect not seen in FXR-/- mice. This compound significantly suppresses the expression of the CYP8B1 bile acid synthetic gene in wild-type mice, showcasing its regulatory impact on bile acid synthesis, though it has no effect on CYP8B1 gene expression in FXR-/- mice[3].
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