the purpose of this proposal is to extend the results from a phase 1 STTR and characterize the in vivo efficacy of thrombostatin, a novel peptide that inhibits gamma-thrombin from activating platelets. Thrombostatin will be tested alone and as part of combination therapy with aspirin or clopidagrel for acute coronary syndromes. The rationale for developing this type of thrombin inhibitor relates to the fact that this class of agents interacts exclusively with the active site as well as with thrombin receptors on platelets (PAR1). There is much less activity on components of the coagulation cascade. The two specific aims of this phase II STTR are to determine if thrombostatin is additive to intravenous aspirin and clopidagrel therapy to prevent electrolytic-induced canine coronary artery thrombosis. Second the investigators will examine a library of compounds with the goal of identifying a more potent thrombostatin for in vivo toxicology in animals and humans. The applicant states that current anticoagulants and antiplatelet regimens achieved at best a 10-56% reduction in adverse events in the management of acute coronary artery syndromes. The addition of a new class of platelet-selective antithrombotic agents may improve upon the results of current therapy for acute coronary syndromes.
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