Obeticholic acid

Obeticholic acid (INT-747) is a potent, selective and orally active FXR agonist with an EC₅₀ of 99 nM. Obeticholic acid has anticholeretic and anti-inflammation effect. Obeticholic acid also induces autophagy^[1][2][3]. IC50 & Target:EC50: 99 nM (FXR) In Vitro: Obeticholic acid (INT-747) increases the expression of FXR-regulated genes in rat hepatocytes^[1]. Obeticholic acid (INT-747) reduces expression of liver JNK-1 and JNK-2^[2]. Obeticholic acid (INT-747) (256 μg/mL) shows complete inhibition of bacterial growth in all strains tested. Intestinal permeability remains unaffected after INT-747-addition to an IFN-γ-exposed intestinal epithelium of Caco-2 cells^[3]. In Vivo: Obeticholic acid (INT-747) (10 mg/kg/day) completely reverted cholestasis induced by E₂17α. Administration of Obeticholic acid (INT-747) partially prevents the impairment in total bile acid output caused by E₂17α by increasing the relative abundance of β-MCA and TCDCA and TDCA^[1]. Obeticholic acid (INT-747)7 (10 mg/kg) and HS increases the pulmonary congestion in the animals. INT-747 does not improve renal pathology in the HS-fed animals^[2]. Obeticholic acid (INT-747) (5 mg/kg) significantly increases survival in BDL rats. Obeticholic acid (INT-747)-treated BDL rats exhibits a significant selective ileal increase in expression of pore-closing claudin-1. Ileal expression of ZO-1 is significantly up-regulated in INT-747-treated BDL rats^[3].