ArticleNature communications2015
Synergistic activation of human pregnane X receptor by binary cocktails of pharmaceutical and environmental compounds.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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Who cites it
66 citing papers in PubMed, 159 citations in OpenAlex.
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- Mechanism-based new approach methodologies for in vitro detection of chemical-induced liver steatosis.Archives of toxicology · 2026Review
- The landscape of biased agonism in aryl hydrocarbon receptor signaling: current clues and future directions.Frontiers in pharmacology · 2026Review
- Endocrine-disrupting chemicals as prostate carcinogens.Nature reviews. Urology · 2025Review
- Mechanisms of altered hepatic drug disposition during pregnancy: small molecules.Expert opinion on drug metabolism & toxicology · 2025Review
- A two-in-one expression construct for biophysical and structural studies of the human pregnane X receptor ligand-binding domain, a pharmaceutical and environmental target.Acta crystallographica. Section F, Structural biology communications · 2025Article
- An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice.Nature communications · 2025Article
- PROTAC-mediated activation, rather than degradation, of a nuclear receptor reveals complex ligand-receptor interaction network.Structure (London, England : 1993) · 2024Article
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- Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR.Nature communications · 2024Article
- Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands.Nature communications · 2024Article
- Impact of perfluoroalkyl substances (PFAS) and PFAS mixtures on lipid metabolism in differentiated HepaRG cells as a model for human hepatocytes.Archives of toxicology · 2024Article
- Cannabidiol promotes intestinal cholesterol uptake mediated by Pregnane X receptor.Frontiers in endocrinology · 2024Article
- Effects of okadaic acid, azaspiracid-1, yessotoxin and their binary mixtures on human intestinal Caco-2 cells.EXCLI journal · 2024Article
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- Structure-guided approach to modulate small molecule binding to a promiscuous ligand-activated protein.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- 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
- Mixture Effects of Tryptophan Intestinal Microbial Metabolites on Aryl Hydrocarbon Receptor Activity.International journal of molecular sciences · 2022Article
- A novel chemo-phenotypic method identifies mixtures of salpn, vitamin D3, and pesticides involved in the development of colorectal and pancreatic cancer.Ecotoxicology and environmental safety · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Humans are chronically exposed to multiple exogenous substances, including environmental pollutants, drugs and dietary components. Many of these compounds are suspected to impact human health, and their combination in complex mixtures could exacerbate their harmful effects. Here we demonstrate that a pharmaceutical oestrogen and a persistent organochlorine pesticide, both exhibiting low efficacy when studied separately, cooperatively bind to the pregnane X receptor, leading to synergistic activation. Biophysical analysis shows that each ligand enhances the binding affinity of the other, so the binary mixture induces a substantial biological response at doses at which each chemical individually is inactive. High-resolution crystal structures reveal the structural basis for the observed cooperativity. Our results suggest that the formation of 'supramolecular ligands' within the ligand-binding pocket of nuclear receptors contributes to the synergistic toxic effect of chemical mixtures, which may have broad implications for the fields of endocrine disruption, toxicology and chemical risk assessment.
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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.