1H. Liver X receptor-like receptors
More information on this family may be found on the IUPHAR-DB family and introduction pages.
Liver X and farnesoid X receptors (LXR and FXR, nomenclature as agreed by NC-IUPHAR Committee on Nuclear Receptors, [6]) are members of a steroid analogue-activated nuclear receptor subfamily (ENSFM00500000269785), which form heterodimers with members of the retinoid X receptor family. Endogenous ligands for LXRs include hydroxycholesterols (OHC), while FXRs appear to be activated by bile acids.
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
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A-González, N; Castrillo, A. (2011) Liver X receptors as regulators of macrophage inflammatory and metabolic pathways. Biochim. Biophys. Acta, 1812 (8): 982-94. [PMID:21193033]
Bełtowski, J; Semczuk, A. (2010) Liver X receptor (LXR) and the reproductive system--a potential novel target for therapeutic intervention. Pharmacol Rep, 62 (1): 15-27. [PMID:20360612]
Calkin, AC; Tontonoz, P. (2010) Liver x receptor signaling pathways and atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 30 (8): 1513-8. [PMID:20631351]
Cariou, B; Staels, B. (2007) FXR: a promising target for the metabolic syndrome?. Trends Pharmacol. Sci., 28 (5): 236-43. [PMID:17412431]
Chen, WD; Wang, YD; Meng, Z; Zhang, L; Huang, W. (2011) Nuclear bile acid receptor FXR in the hepatic regeneration. Biochim. Biophys. Acta, 1812 (8): 888-92. [PMID:21167938]
Claudel, T; Zollner, G; Wagner, M; Trauner, M. (2011) Role of nuclear receptors for bile acid metabolism, bile secretion, cholestasis, and gallstone disease. Biochim. Biophys. Acta, 1812 (8): 867-78. [PMID:21194565]
El-Hajjaji, FZ; Oumeddour, A; Pommier, AJ; Ouvrier, A; Viennois, E; Dufour, J; Caira, F; Drevet, JR; Volle, DH; Baron, S; et al.. (2011) Liver X receptors, lipids and their reproductive secrets in the male. Biochim. Biophys. Acta, 1812 (8): 974-81. [PMID:21334438]
Faulds, MH; Zhao, C; Dahlman-Wright, K. (2010) Molecular biology and functional genomics of liver X receptors (LXR) in relationship to metabolic diseases. Curr Opin Pharmacol, 10 (6): 692-7. [PMID:20829110]
Fiorucci, S; Cipriani, S; Baldelli, F; Mencarelli, A. (2010) Bile acid-activated receptors in the treatment of dyslipidemia and related disorders. Prog. Lipid Res., 49 (2): 171-85. [PMID:19932133]
Fiorucci, S; Rizzo, G; Donini, A; Distrutti, E; Santucci, L. (2007) Targeting farnesoid X receptor for liver and metabolic disorders. Trends Mol Med, 13 (7): 298-309. [PMID:17588816]
Fiévet, C; Staels, B. (2009) Liver X receptor modulators: effects on lipid metabolism and potential use in the treatment of atherosclerosis. Biochem. Pharmacol., 77 (8): 1316-27. [PMID:19101522]
Gabbi, C; Warner, M; Gustafsson, JA. (2009) Minireview: liver X receptor beta: emerging roles in physiology and diseases. Mol. Endocrinol., 23 (2): 129-36. [PMID:19074550]
Gadaleta, RM; van Mil, SW; Oldenburg, B; Siersema, PD; Klomp, LW; van Erpecum, KJ. (2010) Bile acids and their nuclear receptor FXR: Relevance for hepatobiliary and gastrointestinal disease. Biochim. Biophys. Acta, 1801 (7): 683-92. [PMID:20399894]
Gardmo, C; Tamburro, A; Modica, S; Moschetta, A. (2011) Proteomics for the discovery of nuclear bile acid receptor FXR targets. Biochim. Biophys. Acta, 1812 (8): 836-41. [PMID:21439373]
Hageman, J; Herrema, H; Groen, AK; Kuipers, F. (2010) A role of the bile salt receptor FXR in atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 30 (8): 1519-28. [PMID:20631352]
Kemper, JK. (2011) Regulation of FXR transcriptional activity in health and disease: Emerging roles of FXR cofactors and post-translational modifications. Biochim. Biophys. Acta, 1812 (8): 842-50. [PMID:21130162]
Kuipers, F; Stroeve, JH; Caron, S; Staels, B. (2007) Bile acids, farnesoid X receptor, atherosclerosis and metabolic control. Curr. Opin. Lipidol., 18 (3): 289-97. [PMID:17495603]
Lefebvre, P; Cariou, B; Lien, F; Kuipers, F; Staels, B. (2009) Role of bile acids and bile acid receptors in metabolic regulation. Physiol. Rev., 89 (1): 147-91. [PMID:19126757]
Mencarelli, A; Fiorucci, S. (2010) FXR an emerging therapeutic target for the treatment of atherosclerosis. J. Cell. Mol. Med., 14 (1-2): 79-92. [PMID:20041971]
Moore, DD; Kato, S; Xie, W; Mangelsdorf, DJ; Schmidt, DR; Xiao, R; Kliewer, SA. (2006) International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor. Pharmacol. Rev., 58 (4): 742-59. [PMID:17132852]
Schmuth, M; Jiang, YJ; Dubrac, S; Elias, PM; Feingold, KR. (2008) Thematic review series: skin lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology. J. Lipid Res., 49 (3): 499-509. [PMID:18182682]
Wang, YD; Chen, WD; Moore, DD; Huang, W. (2008) FXR: a metabolic regulator and cell protector. Cell Res., 18 (11): 1087-95. [PMID:18825165]
Zhang, Y; Edwards, PA. (2008) FXR signaling in metabolic disease. FEBS Lett., 582 (1): 10-8. [PMID:18023284]
Zollner, G; Trauner, M. (2009) Nuclear receptors as therapeutic targets in cholestatic liver diseases. Br. J. Pharmacol., 156 (1): 7-27. [PMID:19133988]
1. Collins, JL; Fivush, AM; Watson, MA; Galardi, CM; Lewis, MC; Moore, LB; Parks, DJ; Wilson, JG; Tippin, TK; Binz, JG; Plunket, KD; Morgan, DG; Beaudet, EJ; Whitney, KD; Kliewer, SA; Willson, TM. (2002) Identification of a nonsteroidal liver X receptor agonist through parallel array synthesis of tertiary amines. J. Med. Chem., 45 (10): 1963-6. [PMID:11985463]
2. Downes, M; Verdecia, MA; Roecker, AJ; Hughes, R; Hogenesch, JB; Kast-Woelbern, HR; Bowman, ME; Ferrer, JL; Anisfeld, AM; Edwards, PA; Rosenfeld, JM; Alvarez, JG; Noel, JP; Nicolaou, KC; Evans, RM. (2003) A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol. Cell, 11 (4): 1079-92. [PMID:12718892]
3. Lehmann, JM; Kliewer, SA; Moore, LB; Smith-Oliver, TA; Oliver, BB; Su, JL; Sundseth, SS; Winegar, DA; Blanchard, DE; Spencer, TA; Willson, TM. (1997) Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J. Biol. Chem., 272 (6): 3137-40. [PMID:9013544]
4. Makishima, M; Okamoto, AY; Repa, JJ; Tu, H; Learned, RM; Luk, A; Hull, MV; Lustig, KD; Mangelsdorf, DJ; Shan, B. (1999) Identification of a nuclear receptor for bile acids. Science, 284 (5418): 1362-5. [PMID:10334992]
5. Maloney, PR; Parks, DJ; Haffner, CD; Fivush, AM; Chandra, G; Plunket, KD; Creech, KL; Moore, LB; Wilson, JG; Lewis, MC; Jones, SA; Willson, TM. (2000) Identification of a chemical tool for the orphan nuclear receptor FXR. J. Med. Chem., 43 (16): 2971-4. [PMID:10956205]
6. Moore, DD; Kato, S; Xie, W; Mangelsdorf, DJ; Schmidt, DR; Xiao, R; Kliewer, SA. (2006) International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor. Pharmacol. Rev., 58 (4): 742-59. [PMID:17132852]
7. Otte, K; Kranz, H; Kober, I; Thompson, P; Hoefer, M; Haubold, B; Remmel, B; Voss, H; Kaiser, C; Albers, M; Cheruvallath, Z; Jackson, D; Casari, G; Koegl, M; Pääbo, S; Mous, J; Kremoser, C; Deuschle, U. (2003) Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol. Mol. Cell. Biol., 23 (3): 864-72. [PMID:12529392]
8. Parks, DJ; Blanchard, SG; Bledsoe, RK; Chandra, G; Consler, TG; Kliewer, SA; Stimmel, JB; Willson, TM; Zavacki, AM; Moore, DD; Lehmann, JM. (1999) Bile acids: natural ligands for an orphan nuclear receptor. Science, 284 (5418): 1365-8. [PMID:10334993]
9. Pellicciari, R; Fiorucci, S; Camaioni, E; Clerici, C; Costantino, G; Maloney, PR; Morelli, A; Parks, DJ; Willson, TM. (2002) 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity. J. Med. Chem., 45 (17): 3569-72. [PMID:12166927]
10. Repa, JJ; Turley, SD; Lobaccaro, JA; Medina, J; Li, L; Lustig, K; Shan, B; Heyman, RA; Dietschy, JM; Mangelsdorf, DJ. (2000) Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers. Science, 289 (5484): 1524-9. [PMID:10968783]
11. Wu, J; Xia, C; Meier, J; Li, S; Hu, X; Lala, DS. (2002) The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Mol. Endocrinol., 16 (7): 1590-7. [PMID:12089353]
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T0901317 [10] and GW3965 [1] are synthetic agonists acting at both LXRα and LXRβ with less than 10-fold selectivity.