ArticleProceedings of the National Academy of Sciences of the United States of America2017
Structural basis for specific ligation of the peroxisome proliferator-activated receptor δ.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 65 citations in OpenAlex.
- Deciphering the relational dynamics of AF-2 domain of PAN PPAR through drug repurposing and comparative simulations.PloS one · 2023Trial
- Highlights on U.S. FDA-approved halogen-containing drugs in 2024.European journal of medicinal chemistry · 2025Review
- Automated design of multi-target ligands by generative deep learning.Nature communications · 2024Article
- Molecular pathways involved in the control of contractile and metabolic properties of skeletal muscle fibers as potential therapeutic targets for Duchenne muscular dystrophy.Frontiers in physiology · 2024Review
- Highly potent and selective PPARδ agonist reverses memory deficits in mouse models of Alzheimer's disease.Theranostics · 2024Article
- Functional and Structural Insights into the Human PPARα/δ/γ Targeting Preferences of Anti-NASH Investigational Drugs, Lanifibranor, Seladelpar, and Elafibranor.Antioxidants (Basel, Switzerland) · 2023Article
- Ligand dependent interaction between PC-TP and PPARδ mitigates diet-induced hepatic steatosis in male mice.Nature communications · 2023Article
- Macakurzin C Derivatives as a Novel Pharmacophore for Pan-Peroxisome Proliferator-Activated Receptor Modulator.Biomolecules & therapeutics · 2023Article
- Peptide Helix-YPPAR research · 2023Article
- Translating atherosclerosis research from bench to bedside: navigating the barriers for effective preclinical drug discovery.Clinical science (London, England : 1979) · 2022Article
- Exploring Ligand Binding Domain Dynamics in the NRs Superfamily.International journal of molecular sciences · 2022Article
- Design, Synthesis, and Biological Activity of l-1'-Homologated Adenosine Derivatives.ACS medicinal chemistry letters · 2022Article
- Functional and Structural Insights into Human PPARα/δ/γ Subtype Selectivity of Bezafibrate, Fenofibric Acid, and Pemafibrate.International journal of molecular sciences · 2022Article
- Crystal structures of the ligand-binding domain of human peroxisome proliferator-activated receptor δ in complexes with phenylpropanoic acid derivatives and a pyridine carboxylic acid derivative.Acta crystallographica. Section F, Structural biology communications · 2022Article
- Mechanistic Insights into Biological Activities of Polyphenolic Compounds from Rosemary Obtained by Inverse Molecular Docking.Foods (Basel, Switzerland) · 2021Article
- The role of peroxisome proliferator-activated receptors in healthy and diseased eyes.Experimental eye research · 2021Review
- Co-Incubation with PPARβ/δ Agonists and Antagonists Modeled Using Computational Chemistry: Effect on LPS Induced Inflammatory Markers in Pulmonary Artery.International journal of molecular sciences · 2021Article
- Discovery and Structure-Activity Relationships of Novel Template, Truncated 1'-Homologated Adenosine Derivatives as Pure Dual PPARγ/δ Modulators.Journal of medicinal chemistry · 2020Article
- Synthesis, Molecular Modeling and Biological Evaluation of Metabolically Stable Analogues of the Endogenous Fatty Acid Amide Palmitoylethanolamide.International journal of molecular sciences · 2020Article
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11 authors at 2 institutions in 1 country.
Funding
Abstract
The peroxisome proliferator-activated receptor (PPAR) family comprises three subtypes: PPARα, PPARγ, and PPARδ. PPARδ transcriptionally modulates lipid metabolism and the control of energy homeostasis; therefore, PPARδ agonists are promising agents for treating a variety of metabolic disorders. In the present study, we develop a panel of rationally designed PPARδ agonists. The modular motif affords efficient syntheses using building blocks optimized for interactions with subtype-specific residues in the PPARδ ligand-binding domain (LBD). A combination of atomic-resolution protein X-ray crystallographic structures, ligand-dependent LBD stabilization assays, and cell-based transactivation measurements delineate structure-activity relationships (SARs) for PPARδ-selective targeting and structural modulation. We identify key ligand-induced conformational transitions of a conserved tryptophan side chain in the LBD that trigger reorganization of the H2'-H3 surface segment of PPARδ. The subtype-specific conservation of H2'-H3 sequences suggests that this architectural remodeling constitutes a previously unrecognized conformational switch accompanying ligand-dependent PPARδ transcriptional regulation.
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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.