ArticleNature communications2024
Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
13 citing papers in PubMed.
- Rifamycin Structural Modifications Attenuate PXR Binding and CYP3A4 Induction.Journal of medicinal chemistry · 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
- 3-Indolepropionic acid confers PXR-p53 binding to mitigate deoxynivalenol-induced hepatocyte apoptosis.Science China. Life sciences · 2025Article
- Targeting pregnane X receptor with a potent agonist-based PROTAC to delay colon cancer relapse.Oncogenesis · 2025Article
- Mechanisms and Therapeutic Advances of PXR in Metabolic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Calcitriol Induces Paraoxonase 1 Expression in HepG2 Cells: Possible Involvement of VDR-Dependent and Alternative Pathways.International journal of molecular sciences · 2025Article
- Discovery of PXR Antagonist MI891 and PXR Degrader MI1013 and Their Roles in Hepatic Gene Regulation.Journal of medicinal chemistry · 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
- An abundant ginger compound furanodienone alleviates gut inflammation via the xenobiotic nuclear receptor PXR in mice.Nature communications · 2025Article
- First-in-Class Small Molecule Degrader of Pregnane X Receptor Enhances Chemotherapy Efficacy.Journal of medicinal chemistry · 2024Article
- Retinoid X receptor heterodimers in hepatic function: structural insights and therapeutic potential.Frontiers in pharmacology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
Nuclear receptors are ligand-activated transcription factors that can often be useful drug targets. Unfortunately, ligand promiscuity leads to two-thirds of receptors remaining clinically untargeted. PXR is a nuclear receptor that can be activated by diverse compounds to elevate metabolism, negatively impacting drug efficacy and safety. This presents a barrier to drug development because compounds designed to target other proteins must avoid PXR activation while retaining potency for the desired target. This problem could be avoided by using PXR antagonists, but these compounds are rare, and their molecular mechanisms remain unknown. Here, we report structurally related PXR-selective agonists and antagonists and their corresponding co-crystal structures to describe mechanisms of antagonism and selectivity. Structural and computational approaches show that antagonists induce PXR conformational changes incompatible with transcriptional coactivator recruitment. These results guide the design of compounds with predictable agonist/antagonist activities and bolster efforts to generate antagonists to prevent PXR activation interfering with other drugs.
Indexed as
Identifiers
What OpenQuestion holds
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.