ArticleiScience2018
PPARγ in Complex with an Antagonist and Inverse Agonist: a Tumble and Trap Mechanism of the Activation Helix.
Article in iScience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 70 citations in OpenAlex.
- Article
- Molecular Dynamics of PPAR Nuclear Receptors: From Ligand Binding to Transcriptional Regulation.Cells · 2026Review
- Distinctive Behavior and Selective Modulation of PPARγ by Pentacyclic Triterpenoid Pomolic Acid and Hederagenin fromJournal of agricultural and food chemistry · 2026Article
- PPGBioPred: a webserver for predicting the bioactivity of compounds against PPARγ involved in the negative regulation of the Wnt/β-catenin signaling pathway.Molecular diversity · 2026Article
- Predicting peroxisome proliferator-activated receptor gamma potency of small molecules: a synergistic consensus model and deep learning binding affinity approach powered by Enalos Cloud Platform.Molecular diversity · 2026Article
- Multiple binding modes underlieFrontiers in bioinformatics · 2026Article
- Structural determinants of non-covalent PPARγ inverse agonism and their therapeutic implications.Nature communications · 2025Article
- PPARγ modulator predictor (PGMP_v1): chemical space exploration and computational insights for enhanced type 2 diabetes mellitus management.Molecular diversity · 2025Article
- Competitive Ligand-Induced Recruitment of Coactivators to Specific PPARα/δ/γ Ligand-Binding Domains Revealed by Dual-Emission FRET and X-Ray Diffraction of Cocrystals.Antioxidants (Basel, Switzerland) · 2025Article
- From Apo to Ligand-Bound: Unraveling PPARγ-LBD Conformational Shifts via Advanced Molecular Dynamics.ACS omega · 2025Article
- Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.Nature communications · 2025Article
- Article
- Integrative in-silico and in-vitro analysis of taurine and vitamin B12 in modulating PPARγ and Wnt signaling in hyperhomocysteinemia-induced osteoporosis.Biology direct · 2024Article
- Article
- Identification of Novel PPARγ Partial Agonists Based on Virtual Screening Strategy: In Silico and In Vitro Experimental Validation.Molecules (Basel, Switzerland) · 2024Article
- Unanticipated mechanisms of covalent inhibitor and synthetic ligand cobinding to PPARγ.bioRxiv : the preprint server for biology · 2024Article
- Chemogenomics for NR1 nuclear hormone receptors.Nature communications · 2024Article
- Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.bioRxiv : the preprint server for biology · 2024Article
- PPARγ Modulators in Lung Cancer: Molecular Mechanisms, Clinical Prospects, and Challenges.Biomolecules · 2024Review
- International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.Pharmacological reviews · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Peroxisome proliferator activated receptor γ (PPARγ) is a nuclear receptor and target for antidiabetics that increase insulin sensitivity. Owing to the side effects of PPARγ full agonists, research has recently focused on non-activating ligands of PPARγ, which increase insulin sensitivity with decreased side effects. Here, we present the crystal structures of inverse agonist SR10171 and a chemically related antagonist SR11023 bound to the PPARγ ligand-binding domain, revealing an allosteric switch in the activation helix, helix 12 (H12), forming an antagonist conformation in the receptor. H12 interacts with the antagonists to become fixed in an alternative location. Native mass spectrometry indicates that this prevents contacts with coactivator peptides and allows binding of corepressor peptides. Antagonists of related nuclear receptors act to sterically prevent the active configuration of H12, whereas these antagonists of PPARγ alternatively trap H12 in an inactive configuration, which we have termed the tumble and trap mechanism.
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.