دورية أكاديمية
1-Piperidine Propionic Acid as an Allosteric Inhibitor of Protease Activated Receptor-2
| العنوان: | 1-Piperidine Propionic Acid as an Allosteric Inhibitor of Protease Activated Receptor-2 |
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| المؤلفون: | Monica Chinellato, Matteo Gasparotto, Santina Quarta, Mariagrazia Ruvoletto, Alessandra Biasiolo, Francesco Filippini, Luca Spiezia, Laura Cendron, Patrizia Pontisso |
| المصدر: | Pharmaceuticals, Vol 16, Iss 10, p 1486 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Pharmacy and materia medica |
| مصطلحات موضوعية: | G protein-coupled receptors, Protease Activated Receptor 2, allosteric modulator, 1-piperidinepropionic acid, molecular dynamics, Medicine, Pharmacy and materia medica, RS1-441 |
| الوصف: | In the last decades, studies on the inflammatory signaling pathways in multiple pathological contexts have revealed new targets for novel therapies. Among the family of G-protein-coupled Proteases Activated Receptors, PAR2 was identified as a driver of the inflammatory cascade in many pathologies, ranging from autoimmune disease to cancer metastasis. For this reason, many efforts have been focused on the development of potential antagonists of PAR2 activity. This work focuses on a small molecule, 1-Piperidine Propionic Acid (1-PPA), previously described to be active against inflammatory processes, but whose target is still unknown. Stabilization effects observed by cellular thermal shift assay coupled to in-silico investigations, including molecular docking and molecular dynamics simulations, suggested that 1-PPA binds PAR2 in an allosteric pocket of the receptor inactive conformation. Functional studies revealed the antagonist effects on MAPKs signaling and on platelet aggregation, processes mediated by PAR family members, including PAR2. Since the allosteric pocket binding 1-PPA is highly conserved in all the members of the PAR family, the evidence reported here suggests that 1-PPA could represent a promising new small molecule targeting PARs with antagonistic activity. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1424-8247 |
| Relation: | https://www.mdpi.com/1424-8247/16/10/1486; https://doaj.org/toc/1424-8247 |
| DOI: | 10.3390/ph16101486 |
| URL الوصول: | https://doaj.org/article/9292cdb2792e48cdbb95309ec57ce2d8 |
| رقم الأكسشن: | edsdoj.9292cdb2792e48cdbb95309ec57ce2d8 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14248247 |
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| DOI: | 10.3390/ph16101486 |