ArticleProceedings of the National Academy of Sciences of the United States of America1998
Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
237 citing papers in PubMed, 868 citations in OpenAlex.
- Effect of Single Nucleotide Polymorphisms in the Xenobiotic-sensing Receptors NR1I2 and NR1I3 on the Pharmacokinetics and Toxicity of Irinotecan in Colorectal Cancer Patients.Clinical pharmacokinetics · 2016Trial
- Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate.PloS one · 2013Trial
- Ontogeny and sorafenib metabolism.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- The pregnane X receptor agonist St John's Wort has no effects on the pharmacokinetics and pharmacodynamics of repaglinide.Clinical pharmacokinetics · 2011Trial
- Rifamycin Structural Modifications Attenuate PXR Binding and CYP3A4 Induction.Journal of medicinal chemistry · 2026Article
- Effect of enzalutamide on anticoagulant therapy with edoxaban in patients with prostate cancer.British journal of clinical pharmacology · 2026Article
- Subtle changes in ligand-receptor interactions dramatically alter transcriptional outcomes of pregnane X receptor modulators.Structure (London, England : 1993) · 2026Article
- A gut-activated NHR-86-CYP pathway mediates the neuroprotective effects of Enterococcus faecium probiotics in a nematode model of amyotrophic lateral sclerosis.PLoS biology · 2026Article
- Sustained Drug-Drug Interaction Between Cyclosporine and Apalutamide in a Patient With Metastatic Hormone-Sensitive Prostate Cancer: A Case Report and Evaluation of CYP3A4 Induction via Pregnane X Receptor Activation by Apalutamide.Case reports in oncological medicine · 2026Article
- PROTAC repurposing uncovers a noncanonical binding surface that mediates chemical degradation of nuclear receptors.Nature communications · 2025Article
- Cytoplasmic PXR regulates glucose metabolism by binding mRNAs and modulating their stability.Nature structural & molecular biology · 2025Article
- Pregnane X receptor (PXR) as a prognostic marker and therapeutic target in kidney renal clear cell carcinoma (KIRC) via AMPK pathway regulation.Scientific reports · 2025Article
- Development and hepatotoxicity of rifamycin derivatives.Expert opinion on drug metabolism & toxicology · 2025Review
- Development and Verification of a Physiologically Based Pharmacokinetic Model of Furmonertinib and Its Main Metabolite for Drug-Drug Interaction Predictions.CPT: pharmacometrics & systems pharmacology · 2025Article
- Drug-induced cis-regulatory elements in human hepatocytes affect molecular phenotypes associated with adverse reactions.Nature communications · 2025Article
- Recent advances in gut microbiota metabolite regulation of hepatic pregnane X receptor.Frontiers in immunology · 2025Review
- PROTAC-mediated activation, rather than degradation, of a nuclear receptor reveals complex ligand-receptor interaction network.Structure (London, England : 1993) · 2024Article
- First-in-Class Small Molecule Degrader of Pregnane X Receptor Enhances Chemotherapy Efficacy.Journal of medicinal chemistry · 2024Article
- Azole Combinations and Multi-Targeting Drugs That Synergistically InhibitJournal of fungi (Basel, Switzerland) · 2024Review
- Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR.Nature communications · 2024Article
177 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear receptors regulate metabolic pathways in response to changes in the environment by appropriate alterations in gene expression of key metabolic enzymes. Here, a computational search approach based on iteratively built hidden Markov models of nuclear receptors was used to identify a human nuclear receptor, termed hPAR, that is expressed in liver and intestines. hPAR was found to be efficiently activated by pregnanes and by clinically used drugs including rifampicin, an antibiotic known to selectively induce human but not murine CYP3A expression. The CYP3A drug-metabolizing enzymes are expressed in gut and liver in response to environmental chemicals and clinically used drugs. Interestingly, hPAR is not activated by pregnenolone 16alpha-carbonitrile, which is a potent inducer of murine CYP3A genes and an activator of the mouse receptor PXR.1. Furthermore, hPAR was found to bind to and trans-activate through a conserved regulatory sequence present in human but not murine CYP3A genes. These results provide evidence that hPAR and PXR.1 may represent orthologous genes from different species that have evolved to regulate overlapping target genes in response to pharmacologically distinct CYP3A activators, and have potential implications for the in vitro identification of drug interactions important to humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.