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Review
. 2016 Sep;6(5):450-452.
doi: 10.1016/j.apsb.2016.06.011. Epub 2016 Jul 21.

A brief history of the discovery of PXR and CAR as xenobiotic receptors

Jiong Yan  1 , Wen Xie  2
Affiliations
Review

A brief history of the discovery of PXR and CAR as xenobiotic receptors

Jiong Yan et al. Acta Pharm Sin B. 2016 Sep.

Abstract

The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) were cloned and/or established as xenobiotic receptors in 1998. Due to their activities in the transcriptional regulation of phase I and phase II enzymes as well as drug transporters, PXR and CAR have been defined as the master regulators of xenobiotic responses. The discovery of PXR and CAR provides the essential molecular basis by which drugs and other xenobiotic compounds regulate the expression of xenobiotic enzymes and transporters. This article is intended to provide a historical overview on the discovery of PXR and CAR as xenobiotic receptors.

Keywords: CYP2B; CYP2B10; CYP3A; Constitutive androstane receptor; Pregnane X receptor; Xenobiotic receptors.

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Figures

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Graphical abstract
Fig. 1
Figure 1
Summarized functions of PXR and CAR in drug metabolism and energy metabolism. (A) Regulation of drug metabolism by PXR and CAR is achieved by the binding of PXR-RXR or CAR-RXR heterodimers to their binding sites in the promoter regions of drug metabolizing enzymes and transporters. (B) PXR and CAR can regulate energy metabolism by directly regulating genes that are involved in energy metabolism, or by crosstaking with other transcriptional factors (TFs) that are implicated in energy metabolism.
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