Characterizing ligands for farnesoid X receptor – available in vitro test systems for farnesoid X receptor modulator development

Abstract

Introduction: Farnesoid X receptor (FXR) is an ascending target for metabolic and inflammatory diseases. As a nuclear receptor, FXR exhibits many physiological effects in transcription control of several genes. Therefore, the development of synthetic FXR ligands requires elaborate in vitro test systems to characterize novel ligands and to estimate their in vivo activities.

Areas covered: This work gathers and describes published in vitro test systems for FXR ligands including cell-based functional assays as well as binding assays. It also evaluates the information which can be provided by these assays.

Expert opinion: In vitro screening of FXR ligands widely relies on reporter gene assays. Additionally, some co-activator re-cruitment assays are described and for the characterization of potent compounds the pattern of affected target genes is evaluated by qPCR. Compared to other nuclear receptors such as PPARs the variety of test systems is quite low for FXR and might eventually not be enough to sufficiently characterize FXR targeting drug candidates.

Keywords::

• assay
• chenodeoxycholic acid (CDCA)
• coactivator recruitment assay
• farnesoid X receptor
• GW4064
• nuclear receptors
• reporter gene assay

Notes

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