Regulation of CYP3A gene transcription by the pregnane X receptor

Bryan Goodwin, Matthew R. Redinbo, Steven A. Kliewer

Research output: Contribution to journalArticle

303 Citations (Scopus)

Abstract

The pregnane X receptor (PXR) is a promiscuous nuclear receptor that has evolved to protect the body from toxic chemicals. PXR is activated by a structurally diverse collection of xenobiotics, including several widely used prescription drugs. Various lipophilic compounds produced by the body, such as bile acids and steroids, also activate PXR. PXR stimulates the transcription of cytochrome P450 3A monooxygenases and other genes involved in the detoxification and elimination of these potentially harmful chemicals. Assays that detect PXR activation have important implications for the design of future drugs in two respects. On the one hand, PXR activation assays can be used to determine whether candidate drugs are likely to induce CYP3A gene expression and interact with other medicines. On the other hand, PXR agonists may prove useful in the treatment of diseases in which toxic metabolites accumulate, such as cholestatic liver disease.

Original languageEnglish (US)
Pages (from-to)1-23
Number of pages23
JournalAnnual Review of Pharmacology and Toxicology
Volume42
DOIs
StatePublished - 2002

Fingerprint

Cytochrome P-450 CYP3A
Transcription
Genes
Poisons
Assays
Chemical activation
Detoxification
Prescription Drugs
Drug Design
Xenobiotics
Cytoplasmic and Nuclear Receptors
Metabolites
Mixed Function Oxygenases
pregnane X receptor
Bile Acids and Salts
Gene expression
Pharmaceutical Preparations
Liver
Medicine
Liver Diseases

Keywords

  • Bile acids
  • CYP3A
  • Drug interactions
  • Nuclear receptor
  • Xenobiotic metabolism

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Regulation of CYP3A gene transcription by the pregnane X receptor. / Goodwin, Bryan; Redinbo, Matthew R.; Kliewer, Steven A.

In: Annual Review of Pharmacology and Toxicology, Vol. 42, 2002, p. 1-23.

Research output: Contribution to journalArticle

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