Farnesoid X receptor

STD has also been shown to be regulated by farnesoid X receptor (FXR) [34], CAR [35] and liver X receptor (LXR) [36]. Interestingly, all four receptors share the same IR-0 response element to regulate the expression of this S ULT isoform. The hierarchy and relative contribution of individual nuclear receptors in Sult2a regulation remain to be determined. 

Farnesoid X receptor (FXR) and liver X receptors (LXRs) belong to the same NR family as PXR and CAR. Their primary role lies in cholesterol and bile acid metabolism regulation. Like many NRs of this family, FXR heterodimerizes with RXR in vivo [46]. 

Pellicciari, R., Constantino, G. and Fiorucci, S. (2005) Farnesoid X receptor from structure to potential clinical applications. Journal of Medicinal Chemistry, 48, 5383-5403. 

Pellicciari, R., Costantino, G., Camaioni, E., Sadeghpour, B.M., Entrena, A., Willson, T.M., Fiorucci, S., Clerici, C. and Gioielli, A. (2004) Bile acid derivatives as ligands of the farnesoid X receptor. Synthesis, evaluation, and structure-activity relationship of a series of body and... 

Honorio, K.M., Garratt, R.C. and Andricopulo, A.D. (2005) Hologram quantitative structure—activity relationships for a series of farnesoid X receptor activators. Bioorganic Medicinal Chemistry Letters, 15, 3119—3125. 

Bile acids are also natural ligands for the farnesoid X receptor (FXR), a receptor that belongs to the nuclear hormone receptor superfamily. The hydrophobic bile acid chenodeoxycholic acid (CDCA) is the most potent... 

Another example in which literature results were reanalyzed in view of the PSSC concept concerns the development of ligands for the farnesoid X receptor. The farnesoid X receptor is a transcriptional sensor for bile acids, the primary products of cholesterol metabolism, and plays an important role in lipid homeostasis. The farnesoid X receptor was, until recently, an orphan receptor, which means that no specific ligands existed for this receptor. Selective ligands for this receptor have been found in natural product libraries described by Nicolaou et al. The group of Nicolaou developed solid phase synthesis methods to make combinatorial libraries based on a benzopyran core structure. " A 10,000-membered combinatorial library based on the benzopyran core structure was synthesized and screened for activity on the farnesoid X receptor. The first specific ligands for the... 

The farnesoid X receptor is a member of the class of nuclear hormone receptors, which have key roles in development and homeostasis, as well as in many diseases like obesity, diabetes and cancer. The farnesoid X receptor shows structural similarity to the estrogen receptor (ER ), which mediates a broad spectrum of physiological functions such as regulation of reproduction, modulation of bone density, cholesterol transport and breast cancer. The farnesoid X receptor also shows similarity with the peroxisome proliferation-activated receptor y (PPARy), which is involved in fat metabolism, inflammatory and immune responses. The estrogen receptor (ER ), the peroxisome proliferation-activated receptor y (PPARy) and the farnesoid X receptor (FXR) can be clustered in a... 

Wagner M, Fickert P, Zollner G, Fuchsbichler A, Silbert D, Tsybrovskyy O, Zatloukal K, Guo GL, Schuetz JD, Gonzalez FJ, Marschall HU, Denk H, Trauner M. Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice. Gastroenterology 2003 125 825-838. 

Abbreviations. PXR, pregnane X receptor CAR constitutive androstane receptor FXR, farnesoid X receptor. 

Jung D, Podvinec M, Meyer UA, et al. Human organic anion transporting polypeptide 8 promoter is transactivated by the farnesoid X receptor/bile acid receptor. Gastroenterology 2002 122 1954-1966. 

Guo, G.L., Lambert, G., Negishi, M. Ward, J.M., Brewer, H.B., fr., Kliewer, S.A. et al. (2003) Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity. The Journal of Biological Chemistry, 278 (46), 45062-45071. 

Balasubramanian, N., Makishima, M., Mangelsdorf D.J., and Sudiy F.J. (2001) Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile add receptor. The Journal of Biological Chemistry, 276 (31), 28857-28865. 

Honjo, Y., Sasaki, S., Kobayashi, Y, Misawa, H., and Nakamura, H. (2006) 1,25-Dihydroxyvitamin D3 and its receptor inhibit the chenodeoxycholic acid-dependent transactivation by farnesoid X receptor. The Journal of Endocrinology, 188 (3), 635-643. 

---