PAR-1 x PARPBP

PAR1,the prototypical receptor in the family of four G protein-coupled receptors expressed on the surface of a wide variety of cells, is extensively studied- in large part because PAR1 is the major thrombin receptor on human platelets, and antagonists of PAR1 have been developed as novel anti-platelet agents for the prevention of arterial thrombosis.SCH79797 has become the most commonly used exptl. PAR1 antagonist over the last decade, and has been used to study the role of this receptor in a number of settings.Here we report that SCH79797, at concentrations required to achieve meaningful PAR1 antagonism, exerts an important off-target effect on the structure and function of platelets independently of PARs.We confirmed that SCH79797 displayed the potency and selectivity for PAR1 inhibition as previously reported.However, we also show that significant off-target effects - most notably externalisation of PS on the platelet membrane and a disruption of the overall platelet morphol. - were induced following exposure of cells to this drug at concentrations required to achieve PARI antagonism.Findings suggest that SCH79797 exerts important off-target effects on platelets when used at concentrations required to achieve significant levels of PARI antagonism.