fargesone A

Fargesone A is a potent and selective FXR agonist. Fargesone A shows anti-inflammatory activity[1].

Signaling Pathways >> Metabolic Enzyme/Protease >> FXR

Research Areas >> Inflammation/Immunology

FXR[1]

Fargesone A (10 μM; 24 h) 以 FXR 依赖的方式减轻人肝脏 WRL68 细胞的肝细胞紊乱[1]。 Fargesone A 的激动作用是通过与 FXR 的直接相互作用实现的[1]。

Fargesone A (3 and 30 mg/kg; i.p.; daily for 7 days) 可显著改善胆管结扎 (BDL) 诱导的慢性肝纤维化小鼠模型[1]。 Pharmacokinetics parameters of Fargesone A in mice t1/2 (h) Tmax (h) Cmax (ng/mL) AUC0-t (ng/mL*h) AUC0-inf (ng/mL*h) MRT0-inf (h) F (%) i.v. (5 mpk) 0.68±0.1 - 941±57 469±13 471±14 0.43±0.13 - p.o. (10 mpk) 0.33±0.04 0.25±0.00 104±16 101±32 102±32 0.58±0.07 10.8±3.2 Animal Model: C57BL/6 mice, bile duct ligation (BDL)-induced chronic liver fibrosis mouse model[1] Dosage: 3 and 30 mg/kg Administration: IP, once daily for 7 days Result: Resulted in a lower level of inflammatory infiltrates and a smaller amount of collagen deposition compared to the vehicle group. Reversed BDL-induced sharp increase in total bilirubin level in the serum. Significantly decreased liver mRNA expression of the inflammatory biomarkers interleukin (IL)-6, IL-1β, inducible nitric oxide synthase (iNOS), and prostaglandin-endoperoxide synthase 2 (COX2). Animal Model: C57BL6/J mice[1] Dosage: 5 or 10 mg/kg Administration: IV or PO (Pharmacokinetics Analysis) Result: Showed acceptable PK profiles in general.

[1]. Guo F, et al. Biomimetic Total Synthesis and the Biological Evaluation of Natural Product (-)-Fargesone A as a Novel FXR Agonist. JACS Au. 2022 Dec 7;2(12):2830-2838.