Inhibitory Effects of MNS and BDA-410 on Human Platelet Aggregation

Cysteine proteases and tyrosine kinases are two classes of enzymes that have been implicated in the coagulation cascade. This cascade is responsible for the aggregation of human platelets and their role in thrombosis. Understanding the interactions between these two systems is essential in developing treatments to reduce the risk of acute myocardial infarction and ischemic stroke. A modified model for gel-filtered platelet isolation was developed and used in testing a known cysteine protease inhibitor, BDA-410, and a known tyrosine kinase inhibitor, MNS. MNS decreased platelet aggregation as previously reported. BDA-410 also decreased platelet aggregation but required relatively higher concentrations. Importantly, MNS and BDA-410 in combination exerted a near additive effect. Further testing would be required in order to explain the relationship between the two inhibitors on platelet aggregation. Together, these results suggest a role of combination therapy as a potential modality to reduce platelet aggregation and thrombosis in vivo.