New therapy provides faster treatment for heart attacks



Patients experiencing a serious type of heart attack, called ST segment-elevated acute myocardial infarction (STEMI), have improved survival rates if treated within one to two hours after symptoms begin. Drugs called αIIbβ3 receptor antagonists, which inhibit the buildup of blood-clotting cells called platelets, are one currently available treatment, but they must be administered via intravenous therapy (IV) in a hospital setting. Therefore, novel therapeutic interventions are needed in order to improve treatment before arrival at the hospital, which would increase the odds of post-hospital survival.


National Center for Advancing Translational Sciences (NCATS) intramural researchers, working in collaboration with Dr. Barry Coller of Rockefeller University, developed a novel αIIbβ3 antagonist called RUC-4 that can be injected into muscles with an autoinjector, thus allowing for easier administration outside of the hospital. Unlike current small molecule antagonists, RUC-4 was designed based on advanced structural knowledge of the αIIbβ3 receptor, resulting in improved efficacy and fewer undesirable side effects.


RUC-4 substantially reduces the formation of blood clots within five to twenty minutes of administration and begins to wear off within four hours, allowing hospital physicians to choose the most appropriate additional therapy. The drug’s molecular design, efficacy, specificity, ease of administration, and safety profile make it unique in its potential as a pre-hospital therapy for STEMI. RUC-4 is currently in human evaluations.


Li J, Vootukuri S, Shang Y, Negri A, Jiang JK, Nedelman M, Diacova TG, Filizola M, Thomas CJ, Coller BS. (2014). RUC-4: A novel αIIbβ3 antagonist for pre-hospital therapy of myocardial infarction. Arterioscl. Throm. Vas. 34(10): 2321-2329.

Jiang JK, McCoy JG, Shen M, LeClair CA, Huang W, Negri A, Li J, Blue R, Harrington AW, Naini S, David III G, Choi WS, Volpi E, Fernandez J, Babayeva M, Nedelman MA., Filizola M, Coller BS, Thomas CJ. (2014) A novel class of ion displacement ligands as antagonists of the αIIbβ3 receptor that limit conformational reorganization of the receptor. Bioorg. Med. Chem Lett. 24(4):1148-1153.

Zhu J, Choi WS, McCoy JG, Negri A, Zhu,J, Naini S, Li J, Shen M, Huang W, Bougie D, Rasmussen M, Aster R, Thomas CJ, Filizola M, Springer TA, Coller BS. (2012). Structure-guided design of a high-affinity platelet integrin αIIbβ3 receptor antagonist that disrupts Mg²⁺ binding to the MIDAS. Sci. Trans. Med. 4(125):125ra32.

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This page was last updated on Friday, June 9, 2023