Modulators of the Thrombin Receptor PAR-1

In addition to the key role of thrombin in blood coagulation, this multifunctional serine protease activates platelets and regulates the behavior of other cells through G-protein coupled protease activated receptors (PARs). PAR-1 is the principal thrombin-activated receptor involved in platelet aggregation and in endothelial and tumor cell proliferation. PAR-1 is overexpressed in many invasive and metastatic tumors, where the expression levels directly correlate with the degree of invasiveness of the cancer.
The search of new PAR-1 antagonists is one of the goals of our current projects on antitumorals, which we are approaching by applying structure-based and diversity-oriented synthesis strategies.