Farnesoid ligands

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... 

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... 

In such a reverse endocrinology approach the farnesoid X receptor (FXR) could be connected to bile acid ligands. By further exploration of bile acids and other chemical probes for FXR it was discovered that FXR is linked to bile acid homeostasis, and it was postulated that FXR ligands might have beneficial effects for the treatment of cholestatic liver disease and other disorders [50]. 

Bile acids and metabolites are endogenous PXR ligands that activate PXR to metabolize bile acids [49]. This may be a mechanism for detoxifying bile acids in the liver and intestine [50]. Bile acids activate farnesoid X receptor (FXR), which induces expression of small heterodimer partner (SHP), an atypical orphan receptor that lacks the DBD. SHP then inhibits transactivation of CYP7A1 gene by orphan... 

Merk D, Steinhilber D, Schubert-Zsilavecz M (2014) Characterizing ligands for farnesoid X receptor-available in vitro test systems for farnesoid X receptor modulator development. Expert Opin Drug Discov 9 27-37... 

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