{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T16:37:28Z","timestamp":1780850248954,"version":"3.54.1"},"reference-count":33,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-108727RB-I00"],"award-info":[{"award-number":["PID2019-108727RB-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008425","name":"Conseller\u00eda de Cultura, Educaci\u00f3n e Ordenaci\u00f3n Universitaria, Xunta de Galicia","doi-asserted-by":"publisher","award":["Centro Singular de investigaci\u00f3n de Galicia accreditation 2019\u20132022, ED431G 2019\/02; GRC call EDC431C 2018\/21"],"award-info":[{"award-number":["Centro Singular de investigaci\u00f3n de Galicia accreditation 2019\u20132022, ED431G 2019\/02; GRC call EDC431C 2018\/21"]}],"id":[{"id":"10.13039\/501100008425","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Clinical management of ischemic events and prevention of vascular disease is based on antiplatelet drugs. Given the relevance of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) as a candidate target in thrombosis, the main goal of the present study was to identify novel antiplatelet agents within the existing inhibitors blocking PI3K isoforms. Methods: We performed a biological evaluation of the pharmacological activity of PI3K inhibitors in platelets. The effect of the inhibitors was evaluated in intracellular calcium release and platelet functional assays, the latter including aggregation, adhesion, and viability assays. The in vivo drug antithrombotic potential was assessed in mice undergoing chemically induced arterial occlusion, and the associated hemorrhagic risk evaluated by measuring the tail bleeding time. Results: We show that PI3K Class IA inhibitors potently block calcium mobilization in human platelets. The PI3K p110\u03b4 inhibitor Idelalisib inhibits platelet aggregation mediated by ITAM receptors GPVI and CLEC-2, preferentially by the former. Moreover, Idelalisib also inhibits platelet adhesion and aggregation under shear and adhesion to collagen. Interestingly, an antithrombotic effect was observed in mice treated with Idelalisib, with mild bleeding effects at high doses of the drug. Conclusion: Idelalisib may have antiplatelet effects with minor bleeding effects, which provides a rationale to evaluate its antithrombotic efficacy in humans.<\/jats:p>","DOI":"10.3390\/ijms22073304","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T15:42:19Z","timestamp":1616600539000},"page":"3304","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The PI3K\u03b4 Inhibitor Idelalisib Diminishes Platelet Function and Shows Antithrombotic Potential"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1701-6899","authenticated-orcid":false,"given":"Mar\u00eda N.","family":"Barrachina","sequence":"first","affiliation":[{"name":"Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade Santiago de Compostela and Instituto de Investigaci\u00f3n Sanitaria de Santiago, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade Santiago de Compostela and Instituto de Investigaci\u00f3n Sanitaria de Santiago, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Hermida-Nogueira","sequence":"additional","affiliation":[{"name":"Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade Santiago de Compostela and Instituto de Investigaci\u00f3n Sanitaria de Santiago, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5232-3376","authenticated-orcid":false,"given":"Luis A.","family":"Mor\u00e1n","sequence":"additional","affiliation":[{"name":"Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade Santiago de Compostela and Instituto de Investigaci\u00f3n Sanitaria de Santiago, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1999-2487","authenticated-orcid":false,"given":"Amparo","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Pharmacology Applied to Drug Discovery Group, Centro Singular de Investigaci\u00f3n en Medicina Molecular y Enfermedades Cr\u00f3nicas, Universidade Santiago de Compostela, 15705 Santiago de Compostela, Spain"},{"name":"Grupo Biofarma, Instituto de Investigaci\u00f3n Sanitaria de Santiago, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana B.","family":"Arroyo","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB-Arrixaca, CIBERER-U765, 30003 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Garc\u00eda-Barber\u00e1","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB-Arrixaca, CIBERER-U765, 30003 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4772-9822","authenticated-orcid":false,"given":"Roc\u00edo","family":"Gonz\u00e1lez-Conejero","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB-Arrixaca, CIBERER-U765, 30003 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Troiti\u00f1o","sequence":"additional","affiliation":[{"name":"Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade Santiago de Compostela and Instituto de Investigaci\u00f3n Sanitaria de Santiago, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes A.","family":"Eble","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, University of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4225-6840","authenticated-orcid":false,"given":"Jos\u00e9","family":"Rivera","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB-Arrixaca, CIBERER-U765, 30003 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2976-2354","authenticated-orcid":false,"given":"Constantino","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Servicio de Hematolog\u00eda y Oncolog\u00eda M\u00e9dica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonaci\u00f3n, Universidad de Murcia, IMIB-Arrixaca, CIBERER-U765, 30003 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda I.","family":"Loza","sequence":"additional","affiliation":[{"name":"Pharmacology Applied to Drug Discovery Group, Centro Singular de Investigaci\u00f3n en Medicina Molecular y Enfermedades Cr\u00f3nicas, Universidade Santiago de Compostela, 15705 Santiago de Compostela, Spain"},{"name":"Grupo Biofarma, Instituto de Investigaci\u00f3n Sanitaria de Santiago, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3359-5867","authenticated-orcid":false,"given":"Eduardo","family":"Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Pharmacology Applied to Drug Discovery Group, Centro Singular de Investigaci\u00f3n en Medicina Molecular y Enfermedades Cr\u00f3nicas, Universidade Santiago de Compostela, 15705 Santiago de Compostela, Spain"},{"name":"Grupo Biofarma, Instituto de Investigaci\u00f3n Sanitaria de Santiago, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1176-5917","authenticated-orcid":false,"given":"\u00c1ngel","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade Santiago de Compostela and Instituto de Investigaci\u00f3n Sanitaria de Santiago, 15706 Santiago de 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