Analysis of Potential Anticoagulants by Conventional Assays (2015)

Undergraduates: Catherine Keller, Jasmine Dennis

Faculty Advisor: Frank Church
Department: Biology

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Blood clots affect over half a million Americans each year and have a high mortality rate. Current anticoagulants have been historically successful, but can dangerously increase bleeding risk. Using chromogenic substrate assays, I tested almost 1,000 compounds from the Tidwell library of cationic compounds and analyzed their ability to inhibit five specific coagulation proteases. A small number of promising compounds inhibited only one coagulation enzyme. Another member of my lab performed Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT) assays for each of these compounds. Further analysis showed that the compounds that were deemed successful in the PT and APTT had very little overlap with those that successfully inhibited only one coagulation enzyme. These results suggest that current clinical assay methods may not be ideal indicators of thrombotic state. These studies provide useful insight into how to assess successful anticoagulants and will ideally result in a new therapeutic antithrombotic.