title: Pregnane X receptor and drug-induced liver injury.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: St. Jude Children's Research Hospital, Department of Chemical Biology and Therapeutics , 262 Danny Thomas Place, Memphis, TN 38105 , USA.
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Wang
authors.forename: Sergio C
authors.initials: SC
authors.lastname: Chai
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Brewer
authors.forename: Taosheng
authors.initials: T
authors.lastname: Chen
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D015195:Drug Design; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015262:Xenobiotics / Q000009:adverse effects*
chemical_list: D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D015262:Xenobiotics
keywords: adverse drug reaction; drug-induced liver injury; pregnane X receptor; xenobiotic detoxification; xenobiotic receptor