ArticleMolecular pharmacology2019
Mechanistic Insights of Phenobarbital-Mediated Activation of Human but Not Mouse Pregnane X Receptor.
Article in Molecular pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Medications That Regulate Pregnane X Receptor: A Systematic Review of Current Evidence.Pharmacology research & perspectives · 2026Pooled it
- Potent and Selective Human Constitutive Androstane Receptor Activator DL5055 Facilitates Cyclophosphamide-Based Chemotherapies.Journal of medicinal chemistry · 2025Article
- Recent advances in gut microbiota metabolite regulation of hepatic pregnane X receptor.Frontiers in immunology · 2025Review
- Rifampicin-induced challenges in managing endocrine hypertension and primary aldosteronism: a case report and literature review.Frontiers in pharmacology · 2025Article
- A Review of CYP-Mediated Drug Interactions: Mechanisms and In Vitro Drug-Drug Interaction Assessment.Biomolecules · 2024Review
- Phenobarbital in Nuclear Receptor Activation: An Update.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Regulation of Nuclear Receptors PXR and CAR by Small Molecules and Signal Crosstalk: Roles in Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Review
- Clinical Relevance of the Constitutive Androstane Receptor.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Molecular basis of crosstalk in nuclear receptors: heterodimerization between PXR and CAR and the implication in gene regulation.Nucleic acids research · 2022Article
- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Review
- The role of pregnane X receptor (PXR) in substance metabolism.Frontiers in endocrinology · 2022Review
- Phenobarbital Induces SLC13A5 Expression through Activation of PXR but Not CAR in Human Primary Hepatocytes.Cells · 2021Article
- Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning.Cells · 2021Review
- Molecular Mechanisms of the SLC13A5 Gene Transcription.Metabolites · 2021Review
- Metamizole is a Moderate Cytochrome P450 Inducer Via the Constitutive Androstane Receptor and a Weak Inhibitor of CYP1A2.Clinical pharmacology and therapeutics · 2021Article
- Cytochrome P450 expression, induction and activity in human induced pluripotent stem cell-derived intestinal organoids and comparison with primary human intestinal epithelial cells and Caco-2 cells.Archives of toxicology · 2021Article
- The Three-Component Synthesis of 4-Sulfonyl-1,2,3-triazoles via a Sequential Aerobic Copper-Catalyzed Sulfonylation and Dimroth Cyclization.Molecules (Basel, Switzerland) · 2021Article
- Mutation of a single amino acid of pregnane X receptor switches an antagonist to agonist by altering AF-2 helix positioning.Cellular and molecular life sciences : CMLS · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Phenobarbital (PB), a broadly used antiseizure drug, was the first to be characterized as an inducer of cytochrome P450 by activation of the constitutive androstane receptor (CAR). Although PB is recognized as a conserved CAR activator among species via a well-documented indirect activation mechanism, conflicting results have been reported regarding PB regulation of the pregnane X receptor (PXR), a sister receptor of CAR, and the underlying mechanisms remain elusive. Here, we show that in a human CAR (hCAR)-knockout (KO) HepaRG cell line, PB significantly induces the expression of CYP2B6 and CYP3A4, two shared target genes of hCAR and human PXR (hPXR). In human primary hepatocytes and hCAR-KO HepaRG cells, PB-induced expression of CYP3A4 was markedly repressed by genetic knockdown or pharmacological inhibition of hPXR. Mechanistically, PB concentration dependently activates hPXR but not its mouse counterpart in cell-based luciferase assays. Mammalian two-hybrid assays demonstrated that PB selectively increases the functional interaction between the steroid receptor coactivator-1 and hPXR but not mouse PXR. Moreover, surface plasmon resonance binding affinity assay showed that PB directly binds to the ligand binding domain of hPXR (K
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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.