Drug Metabolism Letters

Zhiyang Zhao
Amgen
Cambridge, MA
USA

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Ligand-Dependent Assembly of Pregnane X Receptor, Constitutive Androstane Receptor and Liver X Receptor Is Applicable to Identify Ligands

Author(s): Kaoru Kobayashi, Kosuke Saito, Sachiko Takagi, Kan Chiba.

Abstract:

Pregnane X receptor (PXR), constitutive androstane receptor (CAR) and liver X receptor (LXR) are intracellular sensors for foreign chemicals and/or endogenous compounds. Docking of a ligand into the ligand-binding domain (LBD) of a nuclear receptor induces conformational changes and switches the nuclear receptor into an active conformation. In this study, we examined whether assembly assays to exploit the ligand-dependent interaction of N- and C-terminal regions of the LBD could be used for detection of ligands for PXR, CAR and LXR. Rifampicin, CITCO and T1317 significantly enhanced interactions for human PXR, human CAR and human LXR, respectively. The effects of ligands on the interaction of LBDs in PXR and CAR reflected the species differences in ligand response of PXR and CAR. In conclusion, it appears that the present assay, which exploits the interaction between N- and C-terminal regions of LBDs, is applicable to identify ligands.

Keywords: constitutive androstane receptor, ligand, liver X receptor, mammalian two-hybrid assay, nuclear receptor, pregnane X receptor

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Article Details

VOLUME: 4
ISSUE: 2
Year: 2010
Page: [88 - 94]
Pages: 7
DOI: 10.2174/187231210791292744
Price: $58