{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:13:20Z","timestamp":1791328400870,"version":"4.3.1"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              Platelet Orai1 channels mediate store-operated Ca\n              <jats:sup>2+<\/jats:sup>\n              entry (SOCE), which is required for procoagulant activity and arterial thrombus formation. Pharmacological blockage of these channels may provide a novel way of antithrombotic therapy. Therefore, the thromboprotective effect of SOCE blockers directed against platelet Orai1 is determined.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>Candidate inhibitors were screened for their effects on SOCE in washed human platelets. Tested antagonists included the known compounds, SKF96365, 2-aminoethyl diphenylborate, and MRS1845 and the novel compounds, Synta66 and GSK-7975A. The potency of SOCE inhibition was in the order of Synta66&gt;2-aminoethyl diphenylborate&gt;GSK-7975A&gt;SKF96365&gt;MRS1845. The specificity of the first 3 compounds was verified with platelets from Orai1-deficient mice. Inhibitory activity on procoagulant activity and high-shear thrombus formation was assessed in plasma and whole blood. In the presence of plasma, all 3 compounds suppressed platelet responses and restrained thrombus formation under flow. Using a murine stroke model, arterial thrombus formation was provoked in vivo by transient middle cerebral artery occlusion. Postoperative administration of 2-aminoethyl diphenylborate markedly diminished brain infarct size.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>Plasma-soluble SOCE blockers such as 2-aminoethyl diphenylborate suppress platelet-dependent coagulation and thrombus formation. The platelet Orai1 channel is a novel target for preventing thrombotic events causing brain infarction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.111.243907","type":"journal-article","created":{"date-parts":[[2012,5,12]],"date-time":"2012-05-12T00:14:53Z","timestamp":1336781693000},"page":"1717-1723","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Antithrombotic Potential of Blockers of Store-Operated Calcium Channels in Platelets"],"prefix":"10.1161","volume":"32","author":[{"given":"Roger","family":"van Kruchten","sequence":"first","affiliation":[{"name":"From the Department of Biochemistry and Cardiovascular Centre, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (R.v.K., M.A.H.F., M.J.E.K., E.M.B., J.H.M.H.); Chair of Vascular Medicine, University Clinic, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany (A.B., R.R.-G., B.N.); and Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany (P.K., G.S., C.K)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Braun","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry and Cardiovascular Centre, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (R.v.K., M.A.H.F., M.J.E.K., E.M.B., J.H.M.H.); Chair of Vascular Medicine, University Clinic, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany (A.B., R.R.-G., B.N.); and Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany (P.K., G.S., C.K)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion A. H.","family":"Feijge","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry and Cardiovascular Centre, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (R.v.K., M.A.H.F., M.J.E.K., E.M.B., J.H.M.H.); Chair of Vascular Medicine, University Clinic, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany (A.B., R.R.-G., B.N.); and Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany (P.K., G.S., C.K)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijke J. E.","family":"Kuijpers","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry and Cardiovascular Centre, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (R.v.K., M.A.H.F., M.J.E.K., E.M.B., J.H.M.H.); Chair of Vascular Medicine, University Clinic, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany (A.B., R.R.-G., B.N.); and Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany (P.K., G.S., C.K)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronmy","family":"Rivera-Galdos","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry and Cardiovascular Centre, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (R.v.K., M.A.H.F., M.J.E.K., E.M.B., J.H.M.H.); Chair of Vascular Medicine, University Clinic, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany (A.B., R.R.-G., B.N.); and Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany (P.K., G.S., C.K)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kraft","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry and Cardiovascular Centre, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (R.v.K., M.A.H.F., M.J.E.K., E.M.B., J.H.M.H.); Chair of Vascular Medicine, University Clinic, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany (A.B., R.R.-G., B.N.); and Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany (P.K., G.S., C.K)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Stoll","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry and Cardiovascular Centre, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (R.v.K., M.A.H.F., M.J.E.K., E.M.B., J.H.M.H.); Chair of Vascular Medicine, University Clinic, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany (A.B., R.R.-G., B.N.); and Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany (P.K., G.S., C.K)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kleinschnitz","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry and Cardiovascular Centre, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (R.v.K., M.A.H.F., M.J.E.K., E.M.B., J.H.M.H.); Chair of Vascular Medicine, University Clinic, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany (A.B., R.R.-G., B.N.); and Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany (P.K., G.S., C.K)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edouard M.","family":"Bevers","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry and Cardiovascular Centre, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (R.v.K., M.A.H.F., M.J.E.K., E.M.B., J.H.M.H.); Chair of Vascular Medicine, University Clinic, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany (A.B., R.R.-G., B.N.); and Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany (P.K., G.S., C.K)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Nieswandt","sequence":"additional","affiliation":[{"name":"From the Department of Biochemistry and Cardiovascular Centre, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands (R.v.K., M.A.H.F., M.J.E.K., E.M.B., J.H.M.H.); Chair of Vascular Medicine, University Clinic, and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of W\u00fcrzburg, W\u00fcrzburg, Germany (A.B., R.R.-G., B.N.); and Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany (P.K., G.S., C.K)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan W. 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