Nuclear receptor PXR: discovery of a pharmaceutical anti-target.
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- Record sourced from PubMed, PMID 25831443.
- Also identified by DOI 10.1172/JCI81244 and PMC identifier 4409023.
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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.
Medical subject headings
- Cytochrome P-450 CYP3A
- Cytochrome P-450 CYP3A Inducers
- Receptors, Steroid