{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:28:07Z","timestamp":1787063287020,"version":"build-2736575974"},"reference-count":61,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T00:00:00Z","timestamp":1579564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Bleeding is one of the most critical adverse effects of antithrombotic drugs, and many efforts have been made to discover novel antiplatelet agents without bleeding complications. Shear stress\u2010induced platelet aggregation (SIPA), where the interaction of von Willebrand factor (vWF) and platelet glycoprotein (GP) Ib constitutes the initial step, is a promising target to overcome bleeding problems, as SIPA occurs only in pathological conditions. Here, we describe SP\u20108008, a novel modulator of vWF\u2013GP Ib interactions and evaluated its antiplatelet\/antithrombotic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Newly synthesized compounds were screened for antiplatelet effects in vitro, using human platelets exposed to high shear stress. Aggregation, intracellular calcium level, granule secretion, and integrin activation were assessed. Molecular modelling using virtual docking and flow cytometry were used to evaluate effects on vWF\u2013GP Ib interactions. Antithrombotic effects in vivo were determined in rats, using arterial thrombosis and shear stress\u2010specific thrombosis. Transection tail bleeding time was used to evaluate adverse effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      SP\u20108008 was a potent inhibitor of SIPA, with IC\n                      <jats:sub>50<\/jats:sub>\n                      of 1.44 \u00b1 0.09 \u03bcM. SP\u20108008 effectively and broadly blocked shear stress\u2010induced platelet activation events, without any significant toxicity. Importantly, SP\u20108008 was highly selective against SIPA, effectively interfering with vWF\u2013GP Ib engagement. Most importantly, SP\u20108008 exerted significant antithrombotic effects in vivo in both shear stress\u2010specific and arterial thrombosis, without prolonging bleeding time.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Our results demonstrated that SP\u20108008 can be a novel selective antiplatelet agent with improved safety profile.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.14894","type":"journal-article","created":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T15:48:50Z","timestamp":1571932130000},"page":"929-944","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antithrombotic effect of SP\u20108008, a benzoic acid derivative, through the selective inhibition of shear stress\u2010induced platelet aggregation"],"prefix":"10.1111","volume":"177","author":[{"given":"Thien","family":"Ngo","sequence":"first","affiliation":[{"name":"College of Pharmacy Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keunyoung","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Bian","sequence":"additional","affiliation":[{"name":"College of Pharmacy Seoul National University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gibeom","family":"Nam","sequence":"additional","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University  Suwon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun\u2010Ju","family":"Park","sequence":"additional","affiliation":[{"name":"School of Pharmacy Sungkyunkwan University  Suwon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiho","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy Korea University  Sejong Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geum\u2010Sil","family":"Cho","sequence":"additional","affiliation":[{"name":"Research Headquarters Shin Poong Pharm. 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