ArticleNature communications2014
An alternate binding site for PPARγ ligands.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 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
99 citing papers in PubMed, 192 citations in OpenAlex.
- Interpretable QSAR modelling for PPAR-γ agonist prediction by integrating a stacking strategy, docking, and MD simulations.Molecular diversity · 2026Article
- NMR Studies on Protein-Ligand Interactions.International journal of molecular sciences · 2026Review
- Molecular Dynamics of PPAR Nuclear Receptors: From Ligand Binding to Transcriptional Regulation.Cells · 2026Review
- Evaluation of 3',4'-Di-Biomolecules · 2026Article
- Towards a unified molecular mechanism for ligand-dependent activation of NR4A-RXR heterodimers.eLife · 2026Article
- Article
- Molecular dynamics analysis of a docking-derived baicalein-PPARγ ligand-binding-domain model suggests a pocket-associated AF-2-anchor-silent ensemble.Frontiers in molecular biosciences · 2026Article
- Extracellular vesicles fromFrontiers in immunology · 2026Article
- Multiple binding modes underlieFrontiers in bioinformatics · 2026Article
- Small molecule inhibitor of PPARγ acetylation promotes insulin sensitization and browning of white adipose tissue with improved safety.bioRxiv : the preprint server for biology · 2025Article
- Structural Basis of PPARγ-Mediated Transcriptional Repression by the Covalent Inverse Agonist FX-909.Journal of medicinal chemistry · 2025Article
- Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.Nature communications · 2025Article
- Article
- Article
- Unanticipated mechanisms of covalent inhibitor and synthetic ligand cobinding to PPARγ.bioRxiv : the preprint server for biology · 2024Article
- A new mode of inhibition.eLife · 2024Article
- Cladosporols and PPARγ: Same Gun, Same Bullet, More Targets.Biomolecules · 2024Review
- Article
- A Combined Molecular Dynamics and Hydropathic INTeraction (HINT) Approach to Investigate Protein Flexibility: The PPARγ Case Study.Molecules (Basel, Switzerland) · 2024Article
- Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.bioRxiv : the preprint server for biology · 2024Article
39 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
11 authors at 1 institution in 1 country.
Funding
Abstract
PPARγ is a target for insulin-sensitizing drugs such as glitazones, which improve plasma glucose maintenance in patients with diabetes. Synthetic ligands have been designed to mimic endogenous ligand binding to a canonical ligand-binding pocket to hyperactivate PPARγ. Here we reveal that synthetic PPARγ ligands also bind to an alternate site, leading to unique receptor conformational changes that impact coregulator binding, transactivation and target gene expression. Using structure-function studies we show that alternate site binding occurs at pharmacologically relevant ligand concentrations, and is neither blocked by covalently bound synthetic antagonists nor by endogenous ligands indicating non-overlapping binding with the canonical pocket. Alternate site binding likely contributes to PPARγ hyperactivation in vivo, perhaps explaining why PPARγ full and partial or weak agonists display similar adverse effects. These findings expand our understanding of PPARγ activation by ligands and suggest that allosteric modulators could be designed to fine tune PPARγ activity without competing with endogenous ligands.
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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.