ArticleThe Journal of biological chemistry2015
Allosteric Activation of a G Protein-coupled Receptor with Cell-penetrating Receptor Mimetics.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The trial behind it
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Who cites it
19 citing papers in PubMed.
- PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study.Arteriosclerosis, thrombosis, and vascular biology · 2020Trial
- A neurotensin receptor type 1-derived pepducin acts as a biased allosteric modulator to regulate target receptor function.Acta pharmaceutica Sinica. B · 2026Article
- Structural basis of tethered agonism and G protein coupling of protease-activated receptors.Cell research · 2024Article
- Review
- Pepducin ICL1-9-Mediated β2-Adrenergic Receptor-Dependent Cardiomyocyte Contractility Occurs in a GCardiovascular drugs and therapy · 2023Article
- Lipopeptide Pepducins as Therapeutic Agents.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The Evolving Concept of Neuro-Thromboinflammation for Neurodegenerative Disorders and Neurotrauma: A Rationale for PAR1-Targeting Therapies.Biomolecules · 2021Review
- Allosteric Modulator Leads Hiding in Plain Site: Developing Peptide and Peptidomimetics as GPCR Allosteric Modulators.Frontiers in chemistry · 2021Review
- Insights into the Interaction of LVV-Hemorphin-7 with Angiotensin II Type 1 Receptor.International journal of molecular sciences · 2020Article
- Neutrophil Signaling That Challenges Dogmata of G Protein-Coupled Receptor Regulated Functions.ACS pharmacology & translational science · 2020Review
- The parmodulin NRD-21 is an allosteric inhibitor of PAR1 Gq signaling with improved anti-inflammatory activity and stability.Bioorganic & medicinal chemistry · 2019Article
- PAR2 Pepducin-Based Suppression of Inflammation and Itch in Atopic Dermatitis Models.The Journal of investigative dermatology · 2019Article
- Protease-Activated Receptor 1 as Therapeutic Target in Breast, Lung, and Ovarian Cancer: Pepducin Approach.International journal of molecular sciences · 2018Review
- Emerging Paradigm of Intracellular Targeting of G Protein-Coupled Receptors.Trends in biochemical sciences · 2018Review
- Intracellular Receptor Modulation: Novel Approach to Target GPCRs.Trends in pharmacological sciences · 2018Review
- Targeting PAR1: Now What?Trends in pharmacological sciences · 2017Review
- Targeting Liver Fibrosis with a Cell-penetrating Protease-activated Receptor-2 (PAR2) Pepducin.The Journal of biological chemistry · 2016Article
- Cell-Penetrating Pepducin Therapy Targeting PAR1 in Subjects With Coronary Artery Disease.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
- New paradigms in GPCR drug discovery.Biochemical pharmacology · 2015Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
G protein-coupled receptors (GPCRs) are remarkably versatile signaling systems that are activated by a large number of different agonists on the outside of the cell. However, the inside surface of the receptors that couple to G proteins has not yet been effectively modulated for activity or treatment of diseases. Pepducins are cell-penetrating lipopeptides that have enabled chemical and physical access to the intracellular face of GPCRs. The structure of a third intracellular (i3) loop agonist, pepducin, based on protease-activated receptor-1 (PAR1) was solved by NMR and found to closely resemble the i3 loop structure predicted for the intact receptor in the on-state. Mechanistic studies revealed that the pepducin directly interacts with the intracellular H8 helix region of PAR1 and allosterically activates the receptor through the adjacent (D/N)PXXYYY motif through a dimer-like mechanism. The i3 pepducin enhances PAR1/Gα subunit interactions and induces a conformational change in fluorescently labeled PAR1 in a very similar manner to that induced by thrombin. As pepducins can potentially be made to target any GPCR, these data provide insight into the identification of allosteric modulators to this major drug target class.
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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.