SBIR-STTR Award

The purpose of this proposal is to establish the in vivo efficacy of a new class of thrombin inhibitors, thrombostatins. Thrombostatins are a group of agents that prevent alpha and gamma thrombus from activating platelets. Thrombostatins prevent thrombin from activating platelets by preventing thrombin from leaving its receptors. A particular thrombostatin specificity for thrombin's cloned receptors. Thrombostatins represent a new generation of thrombin inhibitors. Such an agent is needed because potent and specific agents which have directed to thrombin itself, have been associated with too much hemorrhage in clinical trials. The goal of this study is to show thrombostatins in vivo efficacy to prevent thrombosis in adult coronary arteries thrombosis model as a single agent or in combination with aspirin. The applicants theorized that this study will create a new class of selected thrombin inhibitors which alone or in combination with other platelet inhabitant agents potential inhibition of thrombosis in the coronary arteries. Such an agent is needed since all present anti-coagulant regimens only achieve a 25 to 40% reduction in adverse advance in acute coronary artery syndromes.

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.