Table 1.
Partial FXR ligands.
| Types | Name | Outcomes | Refs. | |
|---|---|---|---|---|
| Endogenous | Agonist | Androsterone | directly bind to purified hFXR ligand-binding domain (LBD) protein, recruit steroid receptor coactivator protein-1 (SRC-1) coactivator peptide | [235] |
| CDCA | improve glucose metabolism and increase the mRNA expression of BSEP | [40, 44] | ||
| Antagonist | TUDCA | improve glucose metabolism | [43] | |
| 5Alpha-bile alcohols | modulate intestinal lipid absorption and expression of genes involved in the biosynthesis/catabolism of BAs | [236] | ||
| T-βMCA | reduce the TCA-induced expression of FGF 15 in the ileum | [237] | ||
| GUDCA | improve various metabolic endpoints in mice with obesity | [42] | ||
| DCA | promote intestinal inflammation | [238] | ||
| Selective modulators | progesterone metabolite, epiallopregnanolone sulfate | reduce FXR-mediated discharge of BAs and secretion of FGF19. | [239, 240] | |
| lithocholic acid (LCA) | a hydrophobic bile acid and strongly decrease BSEP | [44] | ||
| Synthetic | Agonist Agonist |
GW4064 | completely restores impaired BA way and metabolic syndrome in iron-fed mice. | [241] |
| INT-767 | relieves podocyte injury, mesangial expansion, collagen deposition and tubulointerstitial fibrosis | [214, 242] | ||
| SU5 | regulate lipid metabolism and triglyceride metabolism | [243] | ||
| OCA | alleviated the histological and biochemical features of NASH without cirrhosis | [46] | ||
| 6α-ethyl-24-norcholanyl-23-amine | behave as full FXR agonist endowed with high binding affinity and efficacy | [43] | ||
| fexaramine | reduces systemic inflammation and metabolic improvement in obese mice | [51] | ||
| HEC96719 | show higher FXR selectivity and more favorable tissue distribution dominantly in liver and intestine | [244] | ||
| Nidufexor (LMB763) | regulates FXR-dependent gene in vitro and in vivo | [52] | ||
| BAR502 | reverses steatohepatitis and fibrosis caused by chronic exposure of mice to a high caloric diet | [245] | ||
| tropifexor (LJN452) | reverses developed fibrosis, reduces non-alcoholic fatty liver disease activity scores and liver triglycerides | [246] | ||
| Antagonist | 3-(tert-Butyl)-4-hydroxyphenyl | obtain antagonistic activity of FXR | [247] | |
| 4-({1-[5-({[1-tert-butyl-5-(4-fluorophenyl)-1H-pyrazol-4-yl]carbonyl}amino)-2-chlorobenzyl]piperidin-4-yl}oxy)benzoic acid | induce remarkable beneficial changes in both plasma non-HDL-cholesterol and HDL-cholesterol levels | [248] | ||
| 9,11-seco-cholesterol derivatives | display the best FXR antagonistic activity at the cellular level and decrease the target genes of FXR | [249] | ||
| FLG249 | controls the level of FXR target gene in mouse ileum | [250] | ||
| Natural | Agonist | Farnesol | stimulate growth of MCF-7 breast cancer cell | [251] |
| 20S-protopanaxatriol | ameliorated hepatic inflammation and fibrosis induced by TAA | [252] | ||
| alisol A 23-acetate | antihyperglycemic | [253] | ||
| alisol B 23-acetate | protects against ischemic acute kidney injury (AKI) | [254] | ||
| altenusin | Attenuates NAFLD by reducing the body weight and fat mass | [255] | ||
| Auraptene | Liver protection, anti-inflammatory and antioxidant activities | [243] | ||
| berberine | reducing hepatic gluconeogenesis and lowering blood glucose | [256] | ||
| Calycosin | improve liver steatosis and reduce liver fibrosis | [257] | ||
| Hedragonic acid | protect mice from liver injury induced by acetaminophen overdose and decrease hepatic inflammatory responses | [258] | ||
| dihydroartemisinin | attenuate portal hypertension by targeting HSC contraction | [259] | ||
| hesperidin | Prevent cholestatic liver injury | [260] | ||
| isotschimgine | alleviates nonalcoholic steatohepatitis and fibrosis | [261] | ||
| schaftoside | could attenuate APAP-induced hepatotoxicity by regulating oxidative stress and inflammation | [262] | ||
| Gypenosides | ameliorated NASH | [263] | ||
| Swertiamarin | alleviate cholestasis | [264] | ||
| conicasterol E | triggers BA detoxification | [265] | ||
| cycloastragenol | Reduce fatty diet-induced liver lipid accumulation | [266] | ||
| Ginsenoside Rc | Relieve inflammation and oxidative stress | [267] | ||
| Cafestol | increased fat oxidation and energy expenditure | [268] | ||
| coumestrol | exert beneficial effects on lipid and glucose metabolism | [269] | ||
| Antagonist | Naringin | promoting BA synthesis from cholesterol by upregulating CYP7A1 | [270] | |
| scalarane sesterterpenes | Inhibition of the interaction between FXR and SRC-1 | [271] | ||
| SIPI-7623 | decreased the level of cholesterol and triglyceride | [272] | ||
| Stigmasterol | contribute to BA-induced hepatocyte damage | [273] | ||
| sulfated sterol | Inhibit a subset of FXR regulatory genes in hepatocytes | [274] | ||
| guggulsterone | Reduced liver cholesterol in wild-type mice fed a high cholesterol diet, but not in FXR-deficient mice | [275] | ||
| selective modulators | Oleanolic acid | reduce the biosynthesis of BAs and the cytotoxicity caused by the increase of BAs | [276] |