title: Nuclear receptor PXR: discovery of a pharmaceutical anti-target.
abstract: Transcriptional induction of the gene encoding cytochrome P450 3A oxygenase (CYP3A) causes a prominent class of dangerous drug-drug interactions wherein one drug accelerates the metabolism of another. In our 1998 JCI paper, we reported the cloning of the human nuclear receptor PXR and demonstrated that it mediates CYP3A induction. We determined that PXR is expressed in liver, acts through a DNA response element located in the CYP3A promoter, and is activated by a structurally diverse collection of drugs that induce CYP3A. Our findings revealed the molecular basis for the CYP3A induction class of drug-drug interactions and provided a high-throughput means for screening out drug candidates with this activity.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kliewer
mesh_terms: D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D065701:Cytochrome P-450 CYP3A Inducers / Q000494:pharmacology*; D004347:Drug Interactions / Q000502:physiology; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008024:Ligands; D000077297:Pregnane X Receptor; D011401:Promoter Regions, Genetic; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000266:history* / Q000502:physiology; D015262:Xenobiotics / Q000493:pharmacokinetics
chemical_list: D065701:Cytochrome P-450 CYP3A Inducers; D008024:Ligands; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D015262:Xenobiotics; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A
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