{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T17:31:59Z","timestamp":1772645519329,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MCIN","award":["PRTR-C17.I1"],"award-info":[{"award-number":["PRTR-C17.I1"]}]},{"name":"Fundaci\u00f3n S\u00e9neca","award":["PRTR-C17.I1"],"award-info":[{"award-number":["PRTR-C17.I1"]}]},{"name":"Project NEOAGONCAR (nuevos agonistas del receptor EP3 para el tratamiento y la prevenci\u00f3n cardiovascular)","award":["PRTR-C17.I1"],"award-info":[{"award-number":["PRTR-C17.I1"]}]},{"name":"\u201cFinanciaci\u00f3n estructurada de proyectos de I+D por Agrupaciones de Inter\u00e9s Econ\u00f3mico (A.I.E.)\u201d","award":["PRTR-C17.I1"],"award-info":[{"award-number":["PRTR-C17.I1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The prostaglandin E2 receptor EP3 is emerging as a promising therapeutic target in cardiovascular diseases because of its involvement in vascular inflammation, platelet aggregation, and vasoconstriction. However, selective EP3 ligands with validated biological activities are scarce. In this study, we combined computational and experimental strategies to identify and validate novel EP3 receptor ligands with therapeutic potential. We implemented a high-throughput, structure- and ligand-based virtual screening pipeline, enabling efficient exploration of approved drugs and natural compounds from DrugBank and FooDB libraries. Top-scoring candidates were prioritised based on binding energy and pharmacophoric similarity. Selected hits were subjected to in silico ADME\/Tox profiling using QikProp to identify molecules with favourable pharmacokinetic and safety parameters. TUCA, masoprocol, and pravastatin sodium have emerged as lead candidates and were validated in vitro using endothelial migration and platelet aggregation assays. TUCA exhibited the most consistent inhibitory effect on endothelial migration, whereas masoprocol and hydrocortisone significantly reduced platelet aggregation. These findings establish a multidimensional workflow for the rational identification of EP3 ligands and support their potential use in cardiovascular therapeutics.<\/jats:p>","DOI":"10.3390\/ijms26104879","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T11:54:26Z","timestamp":1747655666000},"page":"4879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Discovery and Functional Validation of EP3 Receptor Ligands with Therapeutic Potential in Cardiovascular Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1985-5319","authenticated-orcid":false,"given":"Jorge-Ricardo","family":"Alonso-Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Structural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), UCAM\u2014Universidad Cat\u00f3lica San Antonio de Murcia, Campus de Murcia, Av. de los Jer\u00f3nimos, 135, 30107 Murcia, Guadalupe, Spain"},{"name":"Health Sciences PhD Program, UCAM\u2014Universidad Cat\u00f3lica San Antonio de Murcia, Campus de Murcia, Av. de los Jer\u00f3nimos, 135, 30107 Murcia, Guadalupe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1948-1022","authenticated-orcid":false,"given":"Silvia","family":"Montoro-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Preclinical Research of Bioactive Compounds and Drugs (PREBIOF), Izpis\u00faa Lab, HiTech, Faculty of Health Sciences, UCAM\u2014Universidad Cat\u00f3lica San Antonio de Murcia, Campus de Murcia, Av. de los Jer\u00f3nimos, 135, 30107 Murcia, Guadalupe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreia-Filipa","family":"Cruz","sequence":"additional","affiliation":[{"name":"Health Sciences PhD Program, UCAM\u2014Universidad Cat\u00f3lica San Antonio de Murcia, Campus de Murcia, Av. de los Jer\u00f3nimos, 135, 30107 Murcia, Guadalupe, Spain"},{"name":"Preclinical Research of Bioactive Compounds and Drugs (PREBIOF), Izpis\u00faa Lab, HiTech, Faculty of Health Sciences, UCAM\u2014Universidad Cat\u00f3lica San Antonio de Murcia, Campus de Murcia, Av. de los Jer\u00f3nimos, 135, 30107 Murcia, Guadalupe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1238-9423","authenticated-orcid":false,"given":"Alicia","family":"Ponce-Valencia","sequence":"additional","affiliation":[{"name":"Faculty of Nursing, UCAM\u2014Universidad Cat\u00f3lica San Antonio de Murcia, Campus de Murcia, Av. de los Jer\u00f3nimos, 135, 30107 Murcia, Guadalupe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Carmena-Bargue\u00f1o","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), UCAM\u2014Universidad Cat\u00f3lica San Antonio de Murcia, Campus de Murcia, Av. de los Jer\u00f3nimos, 135, 30107 Murcia, Guadalupe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4468-7898","authenticated-orcid":false,"given":"Horacio","family":"P\u00e9rez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), UCAM\u2014Universidad Cat\u00f3lica San Antonio de Murcia, Campus de Murcia, Av. de los Jer\u00f3nimos, 135, 30107 Murcia, Guadalupe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/S0140-6736(13)61752-3","article-title":"The Framingham Heart Study and the Epidemiology of Cardiovascular Disease: A Historical Perspective","volume":"383","author":"Mahmood","year":"2014","journal-title":"Lancet Lond. 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