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Expert Opin Drug Metab Toxicol. 2014 Nov;10(11):1521-32. doi: 10.1517/17425255.2014.963555. Epub 2014 Sep 25.

Pregnane X receptor and drug-induced liver injury.

Author information

1
St. Jude Children's Research Hospital, Department of Chemical Biology and Therapeutics , 262 Danny Thomas Place, Memphis, TN 38105 , USA.

Abstract

INTRODUCTION:

The liver plays a central role in transforming and clearing foreign substances. The continuous exposure of the liver to xenobiotics sometimes leads to impaired liver function, referred to as drug-induced liver injury (DILI). The pregnane X receptor (PXR) tightly regulates the expression of genes in the hepatic drug-clearance system and its undesired activation plays a role in DILI.

AREAS COVERED:

This review focuses on the recent progress in understanding PXR-mediated DILI and highlights the efforts made to assess and manage PXR-mediated DILI during drug development.

EXPERT OPINION:

Future efforts are needed to further elucidate the mechanisms of PXR-mediated liver injury, including the epigenetic regulation and polymorphisms of PXR. Novel in vitro models containing functional PXR could improve our ability to predict and assess DILI during drug development. PXR inhibitors may provide chemical tools to validate the potential of PXR as a therapeutic target and to develop drugs to be used in the clinic to manage PXR-mediated DILI.

KEYWORDS:

adverse drug reaction; drug-induced liver injury; pregnane X receptor; xenobiotic detoxification; xenobiotic receptor

PMID:
25252616
PMCID:
PMC4198438
DOI:
10.1517/17425255.2014.963555
[Indexed for MEDLINE]
Free PMC Article

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