{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:26:44Z","timestamp":1790519204520,"version":"4.1.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Treatment of myocardial infarction within the first 1 to 2 hours with a thrombolytic agent, percutaneous coronary intervention, or an \u03b1IIb\u03b23 antagonist decreases mortality and the later development of heart failure. We previously reported on a novel small molecule \u03b1IIb\u03b23 antagonist, RUC-2, that has a unique mechanism of action. We have now developed a more potent and more soluble congener of RUC-2, RUC-4, designed to be easily administered intramuscularly by autoinjector to facilitate its use in the prehospital setting. Here, we report the properties of RUC-4 and the antiplatelet and antithrombotic effects of RUC-2 and RUC-4 in animal models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              RUC-4 was \u224820% more potent than RUC-2 in inhibiting human ADP-induced platelet aggregation and much more soluble in aqueous solutions (60\u201380 mg\/mL). It shared RUC-2\u2019s specificity for \u03b1IIb\u03b23 versus \u03b1V\u03b23, did not prime the receptor to bind fibrinogen, or induce changes in \u03b23 identified by a conformation-specific monoclonal antibody. Both RUC-2 and RUC-4 prevented FeCl\n              <jats:sub>3<\/jats:sub>\n              -induced thrombotic occlusion of the carotid artery in mice and decreased microvascular thrombi in response to laser injury produced by human platelets infused into transgenic mice containing a mutated von Willebrand factor that reacts with human but not mouse platelets. Intramuscular injection of RUC-4 in nonhuman primates at 1.9 and 3.85 mg\/kg led to complete inhibition of platelet aggregation within 15 minutes, with dose-dependent return of platelet aggregation after 4.5 to 24 hours.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>RUC-4 has favorable biochemical, pharmacokinetic, pharmacodynamic, antithrombotic, and solubility properties as a prehospital therapy of myocardial infarction, but the possibility of increased bleeding with therapeutic doses remains to be evaluated.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.114.303724","type":"journal-article","created":{"date-parts":[[2014,8,22]],"date-time":"2014-08-22T04:18:37Z","timestamp":1408681117000},"page":"2321-2329","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":89,"title":["RUC-4"],"prefix":"10.1161","volume":"34","author":[{"given":"Jihong","family":"Li","sequence":"first","affiliation":[{"name":"From the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spandana","family":"Vootukuri","sequence":"additional","affiliation":[{"name":"From the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Shang","sequence":"additional","affiliation":[{"name":"From the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Negri","sequence":"additional","affiliation":[{"name":"From the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-kang","family":"Jiang","sequence":"additional","affiliation":[{"name":"From the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Nedelman","sequence":"additional","affiliation":[{"name":"From the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Diacovo","sequence":"additional","affiliation":[{"name":"From the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Filizola","sequence":"additional","affiliation":[{"name":"From the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig J.","family":"Thomas","sequence":"additional","affiliation":[{"name":"From the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry S.","family":"Coller","sequence":"additional","affiliation":[{"name":"From the Allen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, New York, NY (J.L., S.V., B.S.C.); Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY (Y.S., A.N., M.F.); NIH Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD (J.-k.J., C.J.T.); Ekam Imaging, Boston, MA (M.N.); and Departments of Pediatrics and..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-077891"},{"key":"e_1_3_5_3_2","first-page":"CD002130","article-title":"Platelet glycoprotein IIb\/IIIa blockers during percutaneous coronary intervention and as the initial medical treatment of non-ST segment elevation acute coronary syndromes.","volume":"8","author":"Bosch X","year":"2010","unstructured":"Bosch X, Marrugat J, Sanchis J. 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