BAR502 is a dual GPBAR1 and FXR agonist (IC50s: 0.4 μM and 2 μM).

GPBAR1:0.4 μM, FXR:2 μM

在10 μM浓度下，BAR502无法分别激活GR、PPARγ和LXR，但能激活核受体PXR。BAR502能够在GLUTAg细胞（一种肠内分泌细胞系）中诱导proglucagon mRNA的表达，并且在THP-1细胞中增加cAMP浓度。此外，BAR502在HepG2细胞中诱导OSTα、BSEP和SHP的表达。BAR502在招募SRC-1共激活剂方面显示出非常强大的活性，并且对FXR有很高的亲和力[1]。

在非阻塞性胆汁淤积模型中，BAR502 能够减轻肝损伤而不引起瘙痒。与 BAR502 同时治疗可提高存活率，降低血清碱性磷酸酶水平，并强有力地调节肝脏对经典FXR靶基因（包括OSTα、BSEP、SHP 和 MDR1）的表达，而不引起瘙痒 [2]。BAR502治疗能使体重减轻10%，提高胰岛素敏感性，提升HDL循环水平，同时减少脂肪变性、炎症和纤维化评分，降低SREPB1c、FAS、PPARγ、CD36 及 CYP7A1 mRNA在肝脏的表达。BAR502增强肝脏中SHP和ABCG5的表达，以及在肠道中SHP、FGF15和GLP1的表达。BAR502促进epWAT的棕色化并减轻由CCl4引起的肝纤维化 [3]。

C57BL6 mice 24 weeks old are fed a high-fat diet containing 60% kj fat and fructose in drinking water (42?g/L) or normal diet (6 mice) for 18 weeks. After 10 weeks of HFD, mice are randomized to receive HFD alone (9 mice) or HFD plus BAR502 (15?mg/kg/day) body weight by gavage (9 mice) for 8 weeks. Mice are housed under controlled temperatures (22?°C) and photoperiods (12:12-hour light/dark cycle), allowed unrestricted access to standard mouse chow and tap water and allowed to acclimate to these conditions for at least 5 days before inclusion in an experiment [3].