Target Information
Target General Infomation | |||||
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Target ID |
T51426
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Former ID |
TTDS00272
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Target Name |
Bile acid receptor
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Gene Name |
NR1H4
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Synonyms |
Farnesoid X receptor; Farnesoid X-activated receptor; Farnesol receptor HRR-1; Nuclear farnesoid X receptor; RXR-interacting protein 14; Retinoid X receptor-interacting protein14; NR1H4
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Target Type |
Successful
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Disease | Anticholelithogenic [ICD10: K80] | ||||
Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1] | |||||
Hyperlipidaemia [ICD9: 272.0-272.4; ICD10: E78] | |||||
Insomnia [ICD9: 307.41, 307.42, 327.0, 780.51, 780.52; ICD10: F51.0, G47.0] | |||||
Osteoarthritis [ICD9: 715; ICD10: M15-M19, M47] | |||||
Primary biliary cholangitis [ICD10: K00-K95] | |||||
Type 2 diabetes [ICD9: 250; ICD10: E11] | |||||
Unspecified [ICD code not available] | |||||
Function |
Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
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BioChemical Class |
Nuclear hormone receptor
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Target Validation |
T51426
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UniProt ID | |||||
Sequence |
MVMQFQGLENPIQISPHCSCTPSGFFMEMMSMKPAKGVLTEQVAGPLGQNLEVEPYSQYS
NVQFPQVQPQISSSSYYSNLGFYPQQPEEWYSPGIYELRRMPAETLYQGETEVAEMPVTK KPRMGASAGRIKGDELCVVCGDRASGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCV MDMYMRRKCQECRLRKCKEMGMLAECMYTGLLTEIQCKSKRLRKNVKQHADQTVNEDSEG RDLRQVTSTTKSCREKTELTPDQQTLLHFIMDSYNKQRMPQEITNKILKEEFSAEENFLI LTEMATNHVQVLVEFTKKLPGFQTLDHEDQIALLKGSAVEAMFLRSAEIFNKKLPSGHSD LLEERIRNSGISDEYITPMFSFYKSIGELKMTQEEYALLTAIVILSPDRQYIKDREAVEK LQEPLLDVLQKLCKIHQPENPQHFACLLGRLTELRTFNHHHAEMLMSWRVNDHKFTPLLC EIWDVQ |
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Structure |
1OSH; 1OSK; 3BEJ; 3DCT; 3DCU; 3FLI; 3FXV; 3GD2; 3HC5; 3HC6; 3L1B; 3OKH; 3OKI; 3OLF; 3OMK; 3OMM; 3OOF; 3OOK; 3P88; 3P89; 3RUT; 3RUU; 3RVF; 4II6
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Drugs and Mode of Action | |||||
Drug(s) | Chenodiol | Drug Info | Approved | Anticholelithogenic | [551871] |
Cholic acid - Asklepion | Drug Info | Approved | Unspecified | [551871] | |
Guggulsterone | Drug Info | Approved | Osteoarthritis | [536258], [539790] | |
obeticholic acid | Drug Info | Approved | Primary biliary cholangitis | [889440] | |
Chenodeoxycholate | Drug Info | Phase 2 | Discovery agent | [522682] | |
Turofexorate isopropyl | Drug Info | Phase 1 | Hyperlipidaemia | [548483] | |
obeticholic acid | Drug Info | Clinical trial | Insomnia | [526211] | |
SB-756050 | Drug Info | Discontinued in Phase 2 | Type 2 diabetes | [548743] | |
SKF-97426 | Drug Info | Discontinued in Phase 2 | Hyperlipidaemia | [545280] | |
Agonist | 1,1-bisphosphonate esters | Drug Info | [535129] | ||
22R-hydroxycholesterol | Drug Info | [527938] | |||
Chenodeoxycholate | Drug Info | [535475] | |||
GW4065 | Drug Info | [535475] | |||
Research programme: farnesoid X receptor agonists, Roche | Drug Info | [543895] | |||
SB-756050 | Drug Info | [550963] | |||
SR-45023A (Apomine) | Drug Info | [535129] | |||
Inhibitor | 12-O-deacetyl-12-epi-19-deoxy-21-hydroxyscalarin | Drug Info | [529138] | ||
AGN-34 | Drug Info | [527690] | |||
E-GUGGULSTERONE | Drug Info | [529138] | |||
Fexaramine | Drug Info | [551393] | |||
Modulator | Chenodiol | Drug Info | [556264] | ||
Cholic acid - Asklepion | Drug Info | [556264] | |||
obeticholic acid | Drug Info | [889440] | |||
SKF-97426 | Drug Info | [533930] | |||
Turofexorate isopropyl | Drug Info | [529912] | |||
Antagonist | Guggulsterone | Drug Info | [536996] | ||
Lithocholate | Drug Info | [535475] | |||
Binder | GW4064 | Drug Info | [535475] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Bile secretion | ||||
Pathway Interaction Database | RXR and RAR heterodimerization with other nuclear receptor | ||||
Reactome | Recycling of bile acids and salts | ||||
PPARA activates gene expression | |||||
Endogenous sterols | |||||
WikiPathways | Nuclear Receptors in Lipid Metabolism and Toxicity | ||||
Nuclear Receptors Meta-Pathway | |||||
Farnesoid X Receptor Pathway | |||||
Drug Induction of Bile Acid Pathway | |||||
References | |||||
Ref 522682 | ClinicalTrials.gov (NCT00912301) Cheno Effect on Transit in Health and IBS-C. U.S. National Institutes of Health. | ||||
Ref 526211 | Nuclear receptors and lipid physiology: opening the X-files. Science. 2001 Nov 30;294(5548):1866-70. | ||||
Ref 536258 | Treating insomnia: Current and investigational pharmacological approaches. Pharmacol Ther. 2006 Dec;112(3):612-29. Epub 2006 Jul 28. | ||||
Ref 539790 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2745). | ||||
Ref 545280 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002680) | ||||
Ref 548483 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025892) | ||||
Ref 548743 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800028284) | ||||
Ref 527690 | J Med Chem. 2005 Aug 25;48(17):5383-403.Farnesoid X receptor: from structure to potential clinical applications. | ||||
Ref 527938 | Oxysterol 22(R)-hydroxycholesterol induces the expression of the bile salt export pump through nuclear receptor farsenoid X receptor but not liver X receptor. J Pharmacol Exp Ther. 2006 Apr;317(1):317-25. Epub 2005 Dec 21. | ||||
Ref 529138 | J Nat Prod. 2007 Nov;70(11):1691-5. Epub 2007 Nov 8.Scalarane sesterterpenes from a marine sponge of the genus Spongia and their FXR antagonistic activity. | ||||
Ref 529912 | A synthetic farnesoid X receptor (FXR) agonist promotes cholesterol lowering in models of dyslipidemia. Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G543-52. | ||||
Ref 533930 | SK&F 97426-A a more potent bile acid sequestrant and hypocholesterolaemic agent than cholestyramine in the hamster. Atherosclerosis. 1993 Jun;101(1):51-60. | ||||
Ref 535129 | The nuclear receptors FXR and LXRalpha: potential targets for the development of drugs affecting lipid metabolism and neoplastic diseases. Curr Pharm Des. 2001 Mar;7(4):231-59. | ||||
Ref 535475 | Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity. J Biol Chem. 2002 Aug 30;277(35):31441-7. Epub 2002 Jun 6. | ||||
Ref 536996 | Effect of guggulsterone and cembranoids of Commiphora mukul on pancreatic phospholipase A(2): role in hypocholesterolemia. J Nat Prod. 2009 Jan;72(1):24-8. |
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