Thrombostatin-A Thrombin Receptor Inhibitor

DESCRIPTION (provided by applicant): The purpose of this proposal is for Thromgen, Inc. to transition its preclinical agent, Thrombostatin(tm), into human clinical trials. Thromgen, Inc. has created an agent that is a low affinity direct thrombin inhibitor and a higher affinity binder to the thrombin activation site on both human protease receptor 1 (PAR1) and 4 (PAR4) to prevent thrombin cleavage of these substrates. Both small and large animal studies demonstrate that this agent delays the time to thrombosis in both coronary and carotid artery thrombosis models in both the mouse and dog. Thromgen, Inc. now seeks funding to support toxicology studies for its best agent, Thrombostatin(tm), for the preparation of an Investigator New Drug (IND) application to the FDA. The specific aims are two-fold: Specific Aim #1: Toxicology investigations will be performed in rodent and nonrodent animal species for the preparation of a Thrombostatin(tm) IND application to the FDA for a single intravenous administration. Specific Aim #2: Analytical studies and genotoxicity investigations on the agent will be performed for FDA requirements for an IND application. The purpose of this program is multifaceted. First, the safety of the current Thrombostatin(tm) for human use will be determined. Second, the preparation of an IND application for its human use for one indication will be achieved. Thrombostatin(tm) has the opportunity to be a first-in-its-class thrombin receptor activation antagonist.