ArticleNature communications2018
A structural mechanism for directing corepressor-selective inverse agonism of PPARγ.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
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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.
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Who cites it
42 citing papers in PubMed, 80 citations in OpenAlex.
- PPARγ Signaling in the Central Nervous System: A Review of the Implications in Synaptic Plasticity, Neuroinflammatory and Neoplastic Processes.Neurochemical research · 2026Review
- Dosing PPARγ Activation With Light Using Fast Relaxing Photoswitches.Angewandte Chemie (International ed. in English) · 2026Article
- PPARγ-Dependent Pioglitazone Treatment Suppresses Neuroinflammation and Improves Cognition in Sepsis-Associated Encephalopathy in Mice.CNS neuroscience & therapeutics · 2026Article
- Ligand Drift Rate Descriptor in Receptor Pocket: Molecular Docking Sampling for Differentiating Partial Agonists in Nuclear Receptors.Journal of chemical information and modeling · 2026Article
- FABP4 regulates inflammation and lipid transport via PPARγ signaling pathway in goose primary hepatocytes.Poultry science · 2026Article
- PPARγ signalling pathway: molecular mechanisms and therapeutic potential in ligamentum flavum hypertrophy and lumbar spinal stenosis.Journal of translational medicine · 2026Review
- Evaluation of 3',4'-Di-Biomolecules · 2026Article
- Distinctive Behavior and Selective Modulation of PPARγ by Pentacyclic Triterpenoid Pomolic Acid and Hederagenin fromJournal of agricultural and food chemistry · 2026Article
- Article
- Genomic Crosstalk Between Nuclear Receptors in Hormone-dependent Cancers.Endocrinology · 2025Review
- Gut symbiont-derived ursodeoxycholic acid promotes fatty acid oxidation to protect against renal ischemia-reperfusion injury.Cell reports. Medicine · 2025Article
- Structural Basis of PPARγ-Mediated Transcriptional Repression by the Covalent Inverse Agonist FX-909.Journal of medicinal chemistry · 2025Article
- PPARγ modulator predictor (PGMP_v1): chemical space exploration and computational insights for enhanced type 2 diabetes mellitus management.Molecular diversity · 2025Article
- Disrupting lipid homeostasis with CAV2 in OSCC triggers apoptosis, lipolysis, and mitochondrial dysfunction by transcriptional repression of PPARγ.Cell & bioscience · 2025Article
- PPAR-γ in Melanoma and Immune Cells: Insights into Disease Pathogenesis and Therapeutic Implications.Cells · 2025Review
- Ligand efficacy shifts a nuclear receptor conformational ensemble between transcriptionally active and repressive states.Nature communications · 2025Article
- SETDB1 amplification in osteosarcomas: Insights from its role in healthy tissues and other cancer types.Oncotarget · 2025Review
- Article
- Article
- Unanticipated mechanisms of covalent inhibitor and synthetic ligand cobinding to PPARγ.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Small chemical modifications can have significant effects on ligand efficacy and receptor activity, but the underlying structural mechanisms can be difficult to predict from static crystal structures alone. Here we show how a simple phenyl-to-pyridyl substitution between two common covalent orthosteric ligands targeting peroxisome proliferator-activated receptor (PPAR) gamma converts a transcriptionally neutral antagonist (GW9662) into a repressive inverse agonist (T0070907) relative to basal cellular activity. X-ray crystallography, molecular dynamics simulations, and mutagenesis coupled to activity assays reveal a water-mediated hydrogen bond network linking the T0070907 pyridyl group to Arg288 that is essential for corepressor-selective inverse agonism. NMR spectroscopy reveals that PPARγ exchanges between two long-lived conformations when bound to T0070907 but not GW9662, including a conformation that prepopulates a corepressor-bound state, priming PPARγ for high affinity corepressor binding. Our findings demonstrate that ligand engagement of Arg288 may provide routes for developing corepressor-selective repressive PPARγ ligands.
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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.