HEC96719

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[1].

Signaling Pathways >> Metabolic Enzyme/Protease >> FXR

Research Areas >> Inflammation/Immunology

EC50: 1.37 nM (FXR, TR-FRET), 1.55 nM (FXR, luciferase reporter assay)[1].

HEC96719 (0.5，1.5 和 5 mg/kg；口服，每天 1 次，共 14 天) 通过测定增加成纤维细胞生长因子 15 (FGF15) 的水平证明激活了 FXR[1]. HEC96719 (5 mg/kg；口服，1 次) 增加肝胆盐输出泵 (BSEP) 的水平和回肠中 FGF15 的水平[1]。 HEC96719 (0.1, 0.3 和 1 mg/kg；口服，每日 1 次，持续 6 周) 显著改善非酒精性脂肪性肝炎 (NASH) 症状[1]。 HEC96719 (0.1，0.3 和 1 mg/kg；口服，每日 1 次，持续 4 周) 对改善肝纤维化有效果，且优于奥贝胆酸 (OCA)[1]。 Animal Model: Male ob/ob nonalcoholic steatohepatitis (NASH) mouse models[1] Dosage: 0.1, 0.3 and 1 mg/kg Administration: Oral administration; 0.1, 0.3 and 1 mg/kg, once daily for 6 weeks Result: Decreased levels of serum alanine aminotransferase (ALT) and liver triglyceride (TG), dose-dependently increased NASH activity and reduced NASH activity score. Animal Model: Male C57BL/6 liver fibrosis mouse models[1] Dosage: 0.1, 0.3 and 1 mg/kg Administration: Oral administration; 0.1, 0.3 and 1 mg/kg, once daily for 4 weeks Result: Decreased levels of serum ALT and TBIL, and reduced fibrosis area.

[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.