{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:49:22Z","timestamp":1787003362454,"version":"build-2736575974"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T00:00:00Z","timestamp":1538092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T00:00:00Z","timestamp":1538092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) P2Y\n                    <jats:sub>12<\/jats:sub>\n                    receptor antagonist reduces ischemic events in patients with acute coronary syndrome. Previous evidence from our group, obtained in a preclinical model of recurrent platelet-mediated thrombosis, demonstrated that GLS-409, a diadenosine tetraphosphate derivative that inhibits both P2Y\n                    <jats:sub>1<\/jats:sub>\n                    and P2Y\n                    <jats:sub>12<\/jats:sub>\n                    ADP receptors, may be a novel and promising antiplatelet drug candidate. However, the salutary antiplatelet effects of GLS-409 were accompanied by a trend toward an unfavorable increase in bleeding. The goals of this study were to: 1) provide proof-of-concept that the efficacy of GLS-409 may be maintained at lower dose(s), not accompanied by an increased propensity to bleeding; and 2) establish the extent and kinetics of the reversibility of human platelet inhibition by the agent. Lower doses of GLS-409 were identified that inhibited\n                    <jats:italic>in vivo<\/jats:italic>\n                    recurrent coronary thrombosis with no increase in bleeding time. Human platelet inhibition by GLS-409 was reversible, with rapid recovery of platelet reactivity to ADP, as measured by platelet surface activated GPIIb-IIIa and platelet surface P-selectin. These data support the concept that GLS-409 warrants further, larger-scale investigation as a novel, potential therapy in acute coronary syndromes.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-32797-1","type":"journal-article","created":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T09:44:31Z","timestamp":1537782271000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["GLS-409, an Antagonist of Both P2Y1 and P2Y12, Potently Inhibits Canine Coronary Artery Thrombosis and Reversibly Inhibits Human Platelet Activation"],"prefix":"10.1038","volume":"8","author":[{"given":"Elena","family":"Smolensky Koganov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan D.","family":"Michelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan B.","family":"Yanachkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milka I.","family":"Yanachkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E.","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Przyklenk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Andrew L.","family":"Frelinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,9,28]]},"reference":[{"key":"32797_CR1","doi-asserted-by":"publisher","first-page":"2922","DOI":"10.1093\/eurheartj\/ehr373","volume":"32","author":"C Patrono","year":"2011","unstructured":"Patrono, C. et al. 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The error has been fixed in the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"E. Smolensky Koganov has nothing to disclose. I. B. Yanachkov, M. I. Yanachkova and G. E. Wright, are employees of GLSynthesis, Inc. A. D. Michelson has received grant support from GLSynthesis and Lilly\/Daiichi Sankyo, and served on a steering committee for an AstraZeneca clinical trial. A. L. Frelinger has received grant support from GLSynthesis and Lilly\/Daiichi Sankyo. K. Przyklenk has received grant support from GLSynthesis and serves on the scientific advisory board of Infarct Reduction Technologies, Inc.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"14529"}}