ArticleDrug metabolism and disposition: the biological fate of chemicals2011
Identification of clinically used drugs that activate pregnane X receptors.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 93 citations in OpenAlex.
- Mechanism-based new approach methodologies for in vitro detection of chemical-induced liver steatosis.Archives of toxicology · 2026Review
- Whole Body Physiologically Based Pharmacokinetic Model to Explain A Patient With Drug-Drug Interaction Between Voriconazole and Flucloxacillin.European journal of drug metabolism and pharmacokinetics · 2024Article
- Activation of PXR causes drug interactions with Paxlovid in transgenic mice.Acta pharmaceutica Sinica. B · 2023Article
- Identification of PXR Activators fromDrug metabolism and disposition: the biological fate of chemicals · 2023Article
- Review
- Article
- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- A concise review on hPXR ligand-recognizing residues and structure-based strategies to alleviate hPXR transactivation risk.RSC medicinal chemistry · 2022Review
- Review
- The role of pregnane X receptor (PXR) in substance metabolism.Frontiers in endocrinology · 2022Review
- Identifying CAR Modulators Utilizing a Reporter Gene Assay.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Overcoming the Pregnane X Receptor Liability: Rational Design to Eliminate PXR-Mediated CYP Induction.ACS medicinal chemistry letters · 2021Article
- Ligand binding at the protein-lipid interface: strategic considerations for drug design.Nature reviews. Drug discovery · 2021Review
- A Retrospective Look at the Impact of Binding Site Environment on the Optimization of TRPA1 Antagonists.ACS medicinal chemistry letters · 2021Article
- Targeting Xenobiotic Nuclear Receptors PXR and CAR to Prevent Cobicistat Hepatotoxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Deciphering structural bases of intestinal and hepatic selectivity in targeting pregnane X receptor with indole-based microbial mimics.Bioorganic chemistry · 2021Article
- Arsenic: Various species with different effects on cytochrome P450 regulation in humans.EXCLI journal · 2021Review
- 100 Years of Suramin.Antimicrobial agents and chemotherapy · 2020Review
- Rifampicin, not vitamin E, suppresses parenteral nutrition-associated liver disease development through the pregnane X receptor pathway in piglets.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Assessing the Selectivity of FXR, LXRs, CAR, and RORγ Pharmaceutical Ligands With Reporter Cell Lines.Frontiers in pharmacology · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The pregnane X receptor (PXR) binds xenobiotics and regulates the expression of several drug-metabolizing enzymes and transporters. Human PXR (hPXR) activation and CYP3A4 induction can be involved in drug-drug interactions, resulting in reduced efficacy or increased toxicity. However, there are known species-specific differences with regard to PXR activation that should be taken into account when animal PXR data are extrapolated to humans. We profiled 2816 clinically used drugs from the National Institutes of Health Chemical Genomics Center Pharmaceutical Collection for their ability to activate hPXR and rat PXR (rPXR) at the cellular level, induce human CYP3A4 at the cellular level, and bind human PXR at the protein level. From 6 to 11% of drugs were identified as active across the four assays, which included assay-specific and pan-active compounds. The lowest concordance was observed between the hPXR and rPXR assays, and many compounds active in both assays nonetheless demonstrated significant potency differences between species. Analysis based on clustering potency values demonstrated the greatest activity correlation between the hPXR activation and CYP3A4 induction assays. Structure-activity relationship analysis identified chemical scaffolds that were pan-active (e.g., dihydropyridine calcium channel blockers) and others that were uniquely active in individual assays (e.g., steroids and fatty acids). These results provide important information on PXR activation by clinically used drugs, highlight the species specificity of PXR activation by xenobiotics, and provide a means of prioritizing compounds for follow-up studies and optimization efforts.
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Registered trials
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.