ArticleNature communications2017
SPA70 is a potent antagonist of human pregnane X receptor.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 105 citations in OpenAlex.
- MBind: A Web-Based Platform for Metalloprotein and Nonmetalloprotein Docking with Optional ML Docking Integration.Molecules (Basel, Switzerland) · 2026Article
- Rifamycin Structural Modifications Attenuate PXR Binding and CYP3A4 Induction.Journal of medicinal chemistry · 2026Article
- In silico identification of peptidomimetic inhibitors targeting PXR and RXR interaction to overcome the inactivation of vitamin D in asthma.Molecular diversity · 2026Article
- Dexamethasone-Mediated Regulation of CYP3A4 and UGTs in Human Hepatoma HuH-7 Cells.Fundamental & clinical pharmacology · 2026Article
- Pregnane X Receptor Regulates Human Endocrine System by Inducing Sex Hormone-Binding Globulin Expression.Basic & clinical pharmacology & toxicology · 2026Article
- Hide and seek: targeting nuclear receptor PXR with inhibitors and PROTACs to improve drug efficacy and safety.Expert opinion on therapeutic targets · 2026Article
- Subtle changes in ligand-receptor interactions dramatically alter transcriptional outcomes of pregnane X receptor modulators.Structure (London, England : 1993) · 2026Article
- PROTAC repurposing uncovers a noncanonical binding surface that mediates chemical degradation of nuclear receptors.Nature communications · 2025Article
- Targeting pregnane X receptor with a potent agonist-based PROTAC to delay colon cancer relapse.Oncogenesis · 2025Article
- Development and hepatotoxicity of rifamycin derivatives.Expert opinion on drug metabolism & toxicology · 2025Review
- Discovery of PXR Antagonist MI891 and PXR Degrader MI1013 and Their Roles in Hepatic Gene Regulation.Journal of medicinal chemistry · 2025Article
- Decoding the selective chemical modulation of CYP3A4.Nature communications · 2025Article
- Quantifying expression and metabolic activity of genes regulated by pregnane X receptor in primary human hepatocyte spheroids.PLoS computational biology · 2025Article
- 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
- The hypolipidemic effect of MI-883, the combined CAR agonist/ PXR antagonist, in diet-induced hypercholesterolemia model.Nature communications · 2025Article
- 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
- Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR.Nature communications · 2024Article
- Proanthocyanidin B2 derived metabolites may be ligands for bile acid receptors S1PR2, PXR and CAR: anJournal of biomolecular structure & dynamics · 2024Article
- A bromodomain-independent mechanism of gene regulation by the BET inhibitor JQ1: direct activation of nuclear receptor PXR.Nucleic acids research · 2024Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Many drugs bind to and activate human pregnane X receptor (hPXR) to upregulate drug-metabolizing enzymes, resulting in decreased drug efficacy and increased resistance. This suggests that hPXR antagonists have therapeutic value. Here we report that SPA70 is a potent and selective hPXR antagonist. SPA70 inhibits hPXR in human hepatocytes and humanized mouse models and enhances the chemosensitivity of cancer cells, consistent with the role of hPXR in drug resistance. Unexpectedly, SJB7, a close analog of SPA70, is an hPXR agonist. X-ray crystallography reveals that SJB7 resides in the ligand-binding domain (LBD) of hPXR, interacting with the AF-2 helix to stabilize the LBD for coactivator binding. Differential hydrogen/deuterium exchange analysis demonstrates that SPA70 and SJB7 interact with the hPXR LBD. Docking studies suggest that the lack of the para-methoxy group in SPA70 compromises its interaction with the AF-2, thus explaining its antagonism. SPA70 is an hPXR antagonist and promising therapeutic tool.The xenobiotic-activated human pregnane X receptor (hPXR) regulates drug metabolism. Here the authors develop hPXR modulators, which are of potential therapeutic interest and functionally and structurally characterize the antagonist SPA70 and the structurally related agonist SJB7.
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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.