Odevixibat CAS# 501692-44-0

Odevixibat (A4250) is a potent, selective, and minimally absorbed inhibitor of the ileal bile acid transporter (IBAT, also known as ASBT or SLC10A2), designed to reduce enterohepatic bile acid recirculation. In preclinical studies, odevixibat exhibited nanomolar potency, with IC₅₀ values of 22–41 nM for human and rat ASBT inhibition in cell-based assays. In rats and cynomolgus monkeys, oral administration significantly reduced bile acid reuptake in the ileum, leading to fecal bile acid excretion increases up to 3–5-fold, while serum bile acid levels dropped by ~70–90%. In Mdr2-knockout mice (a model of cholestatic liver disease), chronic odevixibat treatment reduced hepatic bile acid accumulation by >80%, improved plasma liver enzyme markers (ALT, AST, ALP), and decreased histologic evidence of cholestatic injury and fibrosis. Importantly, systemic exposure was minimal (plasma concentrations typically <1% of administered dose), consistent with its localized intestinal mechanism.