HEC96719 is a selective and orally active tricyclic farnesoid X receptor (FXR) agonist with EC50 values of 1.37 and 1.55 nM by time-resolved fluorescence energy transfer (TR-FRET) and luciferase reporter assays, respectively. HEC96719 significantly improves non-alcoholic steatohepatitis (NASH) and liver fibrosis with favorable tissue distribution in liver and intestine. HEC96719 can be used for the research of non-alcoholic steatohepatitis.
HEC96719 (0.5, 1.5 and 5 mg/kg; oral administration, once daily for 14 days) shows in vivo efficacy for the activation of FXR by measuring the increasing level of fibroblast growth factor 15 (FGF15)[1].HEC96719 (5 mg/kg; oral administration, once) increases the level of liver bile salt export pump (BSEP) and ileum FGF15[1].HEC96719 (0.1, 0.3 and 1 mg/kg; oral administration, once daily for 6 weeks) significantly improves NASH symptoms[1].HEC96719 (0.1, 0.3 and 1 mg/kg; oral administration, once daily for 4 weeks) shows efficacy for improving liver fibrosis and has better effects than obeticholic acid (OCA)[1].
References:
[1]. Cao S, et al. Discovery of a tricyclic farnesoid X receptor agonist HEC96719, a clinical candidate for treatment of non-alcoholic steatohepatitis. Eur J Med Chem. 2022 Feb 15;230:114089.