Therapeutic Target Details
| Target ID: | T07 |
| Target Name: | Bile acid receptor |
| Synonyms: | BAR; Farnesoid X-activated receptor; Farnesol receptor HRR-1; FXR; HRR1; Nuclear receptor subfamily 1 group H member 4; Retinoid X receptor-interacting protein 14; RIP14; RXR-interacting protein 14; NR1H4 |
| GENE: | NR1H4 |
| Action: | agonist |
| Class: | Nuclear hormone receptor |
| UniProtKB ID: | Q96RI1 |
| Entry Name: | NR1H4_HUMAN |
| Related Drugs: | Obeticholic Acid; Tropifexor; Ursodeoxycholic acid |
| Mechanism: | Bile acids are natural ligands of the farnesoid X receptor (FXR). Together they regulate lipid and/or glucose homeostasis, promote insulin sensitivity, and potentially regulate liver fibrosis. FXR agonists have been shown to prevent the development of NASH and promote the resolution of NASH and fibrosis in rodent models. |
| Reference (PMIDs): | 25705637; 15860571; 25690590 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D379 | Tropifexor | Chemical drug | DB16343 | FXR agonist | Enhance lipid metabolism | Under clinical trials | Details |
| D381 | Ursodeoxycholic acid | Chemical drug | DB01586 | AKR1C2 inducer | Anti-inflammatory | Under clinical trials | Details |
| Candidate ID | Source ID | Source Type | Compound Type | Candidate Name | Inclusion Criteria | |
|---|---|---|---|---|---|---|
| R0043 | DB00132 | approved; investigational; nutraceutical | small molecule | alpha-Linolenic acid | Therapeutic strategy associated | Details |
| R0564 | DB02509 | experimental | small molecule | Farnesol | Target associated | Details |
| R0565 | DB02545 | experimental | small molecule | Fexaramine | Target associated | Details |
| R0568 | DB02659 | approved | small molecule | Cholic Acid | Target associated | Details |
| R0590 | DB03619 | approved | small molecule | Deoxycholic acid | Therapeutic strategy associated | Details |
| R0601 | DB04348 | approved; experimental | small molecule | Taurocholic acid | Target associated | Details |
| R0607 | DB04557 | experimental | small molecule | Arachidonic Acid | Target associated | Details |
| R1095 | DB06777 | approved | small molecule | Chenodeoxycholic acid | Target associated | Details |
| R1138 | DB08220 | experimental | small molecule | (8alpha,10alpha,13alpha,17beta)-17-[(4-hydroxyphenyl)carbonyl]androsta-3,5-diene-3-carboxylic acid | Target associated | Details |
| R1383 | DB11605 | approved | small molecule | Myrrh | Therapeutic strategy associated | Details |
| Compound ID | Source ID | Source Type | Compound Name | Molecular Weight | Molecular Formula | Molecular Species | |
|---|---|---|---|---|---|---|---|
| B000007 | CHEMBL10041 | Small molecule | AFIMOXIFENE | 387.52 | C26H29NO2 | BASE | Details |
| B000038 | CHEMBL101327 | Small molecule | -- | 545.92 | C28H20ClF4NO4 | ACID | Details |
| B000041 | CHEMBL101381 | Small molecule | -- | 587.3 | C28H22BrCl2NO4 | ACID | Details |
| B000048 | CHEMBL101547 | Small molecule | -- | 522.43 | C29H25Cl2NO4 | ACID | Details |
| B000083 | CHEMBL103 | Small molecule | PROGESTERONE | 314.47 | C21H30O2 | NEUTRAL | Details |
| B000089 | CHEMBL103394 | Small molecule | -- | 522.43 | C29H25Cl2NO4 | ACID | Details |
| B000101 | CHEMBL104 | Small molecule | CLOTRIMAZOLE | 344.85 | C22H17ClN2 | NEUTRAL | Details |
| B000104 | CHEMBL1042 | Small molecule | CHOLECALCIFEROL | 384.65 | C27H44O | NEUTRAL | Details |
| B000153 | CHEMBL105712 | Small molecule | PHENACYL CHLORIDE | 154.6 | C8H7ClO | NEUTRAL | Details |
| B000189 | CHEMBL107 | Small molecule | COLCHICINE | 399.44 | C22H25NO6 | NEUTRAL | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A00022 | 35251469 | Oxid Med Cell Longev | Farnesoid X Receptor Deficiency Induces Hepatic Lipid and Glucose Metabolism Disorder via Regulation of Pyruvate Dehydrogenase Kinase 4. | Details |
| A00107 | 35217817 | Acta Pharmacol Sin | Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease. | Details |
| A00474 | 35068796 | J Clin Exp Hepatol | A Current Understanding of Bile Acids in Chronic Liver Disease. | Details |
| A00655 | 35013582 | Sci Rep | PRMT3 inhibitor SGC707 reduces triglyceride levels and induces pruritus in Western-type diet-fed LDL receptor knockout mice. | Details |
| A00700 | 34998040 | Eur J Med Chem | Discovery of a tricyclic farnesoid X receptor agonist HEC96719, a clinical candidate for treatment of non-alcoholic steatohepatitis. | Details |
| A00797 | 34964117 | Compr Physiol | Bile Acids, Gut Microbiome and the Road to Fatty Liver Disease. | Details |
| A01195 | 34831031 | Cells | Bile Acid Receptors and the Gut-Liver Axis in Nonalcoholic Fatty Liver Disease. | Details |
| A01402 | 34759011 | Drug Metab Dispos | Environmental Chemical Contribution to the Modulation of Bile Acid Homeostasis and Farnesoid X Receptor Signaling. | Details |
| A02213 | 34458376 | J Immunol Res | Probiotics Alleviated Nonalcoholic Fatty Liver Disease in High-Fat Diet-Fed Rats via Gut Microbiota/FXR/FGF15 Signaling Pathway. | Details |
| A02796 | 34236487 | Semin Immunopathol | Role of bile acids in inflammatory liver diseases. | Details |
| A04114 | 33752128 | EBioMedicine | Conjugated secondary 12α-hydroxylated bile acids promote liver fibrogenesis. | Details |
| A04243 | 33692776 | Front Immunol | TGR5 Regulates Macrophage Inflammation in Nonalcoholic Steatohepatitis by Modulating NLRP3 Inflammasome Activation. | Details |
| A04783 | 33506572 | Liver Int | Fibroblast Growth Factor 19: Potential modulation of hepatic metabolism for the treatment of non-alcoholic fatty liver disease. | Details |
| A05346 | 33292701 | Biomark Res | Dysregulated bile acid receptor-mediated signaling and IL-17A induction are implicated in diet-associated hepatic health and cognitive function. | Details |
| A05479 | 33242590 | Biochim Biophys Acta Mol Basis Dis | Regulation of autophagy by bile acids and in cholestasis - CholestoPHAGY or CholeSTOPagy. | Details |
| A06866 | 32717871 | Int J Mol Sci | Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications. | Details |
| A07297 | 32552182 | Expert Opin Investig Drugs | Bile acid modulators for the treatment of nonalcoholic steatohepatitis (NASH). | Details |
| A07424 | 32505776 | Clin Chim Acta | Intestinal microbiota-farnesoid X receptor axis in metabolic diseases. | Details |
| A07880 | 32325178 | J Ethnopharmacol | Qiang-Gan formula extract improves non-alcoholic steatohepatitis via regulating bile acid metabolism and gut microbiota in mice. | Details |
| A08933 | 31931543 | Z Gastroenterol | [What is the (right) target for non-alcoholic fatty liver disease (NAFLD)?] | Details |