{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:39:07Z","timestamp":1773049147705,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rigel Pharmaceuticals","award":["553876"],"award-info":[{"award-number":["553876"]}]},{"name":"Umm Al-Qura University (UQU)","award":["553876"],"award-info":[{"award-number":["553876"]}]},{"name":"Jouf University (JU)","award":["553876"],"award-info":[{"award-number":["553876"]}]},{"name":"Novartis and Principia Biopharma","award":["553876"],"award-info":[{"award-number":["553876"]}]},{"name":"Bayer","award":["553876"],"award-info":[{"award-number":["553876"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>New antithrombotic medications with less effect on haemostasis are needed for the long-term treatment of acute coronary syndromes (ACS). The platelet receptor glycoprotein VI (GPVI) is critical in atherothrombosis, mediating platelet activation at atherosclerotic plaque. The inhibition of spleen tyrosine kinase (Syk) has been shown to block GPVI-mediated platelet function. The aim of our study was to investigate if the Syk inhibitor fostamatinib could be repurposed as an antiplatelet drug, either alone or in combination with conventional antiplatelet therapy. The effect of the active metabolite of fostamatinib (R406) was assessed on platelet activation and function induced by atherosclerotic plaque and a range of agonists in the presence and absence of the commonly used antiplatelet agents aspirin and ticagrelor. The effects were determined ex vivo using blood from healthy volunteers and aspirin- and ticagrelor-treated patients with ACS. Fostamatinib was also assessed in murine models of thrombosis. R406 mildly inhibited platelet responses induced by atherosclerotic plaque homogenate, likely due to GPVI inhibition. The anti-GPVI effects of R406 were amplified by the commonly-used antiplatelet medications aspirin and ticagrelor; however, the effects of R406 were concentration-dependent and diminished in the presence of plasma proteins, which may explain why fostamatinib did not significantly inhibit thrombosis in murine models. For the first time, we demonstrate that the Syk inhibitor R406 provides mild inhibition of platelet responses induced by atherosclerotic plaque and that this is mildly amplified by aspirin and ticagrelor.<\/jats:p>","DOI":"10.3390\/ijms23136982","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T21:25:00Z","timestamp":1656019500000},"page":"6982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Antithrombotic Effects of Fostamatinib in Combination with Conventional Antiplatelet Drugs"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8892-5192","authenticated-orcid":false,"given":"Maan H.","family":"Harbi","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah 24381, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher W.","family":"Smith","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2860-5509","authenticated-orcid":false,"given":"Fawaz O.","family":"Alenazy","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4843-2975","authenticated-orcid":false,"given":"Phillip L. R.","family":"Nicolson","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alok","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve P.","family":"Watson","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark R.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK"},{"name":"Department of Cardiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1056\/NEJMoa1500857","article-title":"Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction","volume":"372","author":"Bonaca","year":"2015","journal-title":"N. 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