FXR agonist 3 is an anti-NASH agent, acting by activating FXR. FXR agonist 3 inhibits COL1A1, TGF-β1, α-SMA and TIMP1 expression with anti-fibrogenic activity. FXR agonist 3 significantly reduces liver steatosis and inflammation, improves liver fibrosis level.
FXR agonist 3 (compound 3a) (5 μM; 24 h) shows anti-fibrogenic activity, decreases multiple fibrogenic biomarkers level in LX-2 cells in a dose-dependent manner[1].
FXR agonist 3 shows cytotoxic concentration against LX2 cells with an CC50 value of 70.36 μM[1].
Metabolic stability of FXR agonist 3 in human, rat and mouse liver microsomes[1]
| Species | T1/2 (h) | CLInt (mic) (μg/min/mg) | CLInt (liver) (μg/min/mg) | Remaining Ratio (%) (T=60 min) |
| Human | 53.3 | 26.0 | 23.4 | 44.1 |
| Rat | 7.4 | 187.8 | 338.0 | 0.4 |
| Mouse | 7.4 | 187.9 | 744.1 | 39.0 |
FXR agonist 3 (compound 3a) (200 mg/kg; p.o.; daily for 4 weeks) significantly attenuates the degree of liver fibrosis in choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD)-induced NASH mice model[1].
FXR agonist 3 (200 mg/kg; p.o.; daily for 4 weeks) also exerts liver-protective and anti-fibrosis activities in bile duct ligation (BDL)-induced fibrosis rat model[1].