Submit a comment

Nuclear receptor PXR: discovery of a pharmaceutical anti-target
Steven A. Kliewer
Steven A. Kliewer
Published April 1, 2015
Citation Information: J Clin Invest. 2015;125(4):1388-1389. https://doi.org/10.1172/JCI81244.
View: Text | PDF
Hindsight

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

Steven A. Kliewer

×

Guidelines

The Editorial Board will only consider comments that are deemed relevant and of interest to readers. The Journal will not post data that have not been subjected to peer review; or a comment that is essentially a reiteration of another comment.

  • Comments appear on the Journal’s website and are linked from the original article’s web page.
  • Authors are notified by email if their comments are posted.
  • The Journal reserves the right to edit comments for length and clarity.
  • No appeals will be considered.
  • Comments are not indexed in PubMed.

Specific requirements

  • Maximum length, 400 words
  • Entered as plain text or HTML
  • Author’s name and email address, to be posted with the comment
  • Declaration of all potential conflicts of interest (even if these are not ultimately posted); see the Journal’s conflict-of-interest policy
  • Comments may not include figures
This field is required
This field is required
This field is required
This field is required
This field is required
This field is required