FXR agonist 3

• CAT Number: I042384
• Molecular Formula: C28H28BrNO4
• Molecular Weight: 522.43
• Purity: ≥95%
• Synonyms: 2,3,10-trimethoxy-9-[(3-methylphenyl)methoxy]-5,6-dihydroisoquinolino[2,1-b]isoquinolin-7-ium;bromide
• InChI: InChI=1S/C28H28NO4.BrH/c1-18-6-5-7-19(12-18)17-33-28-23-16-29-11-10-21-14-26(31-3)27(32-4)15-22(21)24(29)13-20(23)8-9-25(28)30-2;/h5-9,12-16H,10-11,17H2,1-4H3;1H/q+1;/p-1
• InChIKey: ZJDFWYFAYRTEHX-UHFFFAOYSA-M
• SMILES: CC1=CC(=CC=C1)COC2=C(C=CC3=CC4=[N+](CCC5=CC(=C(C=C54)OC)OC)C=C32)OC.[Br-]

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[1].
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].

Reference

[1]. Zhang N, et al. Discovery and development of palmatine analogues as anti-NASH agents by activating farnesoid X receptor (FXR). Eur J Med Chem. 2023 Jan 5;245(Pt 1):114886.
 [Content Brief]