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  • Title: Effect of thrombin inhibitors on platelet functions: comparative analysis of DuP 714 and hirudin.
    Author: Reilly TM, Knabb RM, Hassell SM, Bozarth JM, Forsythe MS, Mayo MC, Racanelli AL, Mousa SA.
    Journal: Blood Coagul Fibrinolysis; 1992 Oct; 3(5):513-7. PubMed ID: 1450317.
    Abstract:
    Since thrombin plays an important role in platelet-mediated arterial thrombosis, we have examined the antiplatelet activity of a synthetic thrombin inhibitor, DuP 714 (Ac-(D)Phe-Pro-boroArg), in comparison with that of the naturally occurring inhibitor hirudin. Hirudin was slightly more potent than DuP 714 in inhibiting thrombin-induced aggregation in washed human platelets (IC50s of 72 nM and 150 nM, respectively) and in inhibiting the secretion of plasminogen activator inhibitor-I from human platelets (IC50s of 300 nM and 900 nM, respectively). In contrast, DuP 714 was more potent than hirudin in inhibiting thrombin-induced [125I]fibrinogen binding to gel purified platelets, and in inhibiting thrombin-induced intracellular calcium mobilization in washed platelets. These results indicate that the tripeptide DuP 714 has comparable antiplatelet activity to the 65 amino acid hirudin. We conclude that DuP 714 may have clinical utility in the prevention of platelet-dependent, arterial thrombotic processes.
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