Inhibiting PAR-1 in the prevention and treatment of atherothrombotic events.
BACKGROUND
Aspirin, an irreversible inhibitor of thromboxane A(2) production, in combination with clopidogrel, an inhibitor of PY(12) ADP platelet receptors, represents the current standard-of-care of antiplatelet therapy for patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. Although these agents have demonstrated significant clinical benefit, the increased risk of bleeding and the recurrence of thrombotic events represent substantial limitations.


METHODS
The inhibition of protease-activated receptors (PAR)-1, is the target for novel antiplatelet drugs, which showed a good safety profile in preclinical studies. The drugs most developed are vorapaxar (SCH530348) and atopaxar (E5555), which will be further evaluated in ongoing Phase III and II clinical trials respectively.


RESULTS
This review is focused on the current knowledge of PAR-1 antagonists, analyzing the pharmacological and early phase clinical investigation findings on these new drugs.


CONCLUSIONS
The PAR-1 receptor offers a new target for the inhibition of platelet activation and aggregation. Preliminary results showed the good safety profile of these new agents. The results of the Phase III ongoing trials will provide important clinical insight into the blockade of thrombin-induced platelet activation.
Tomasello
Salvatore Davide
SD
University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA.
Angiolillo
Dominick J
DJ
Goto
Shinya
S
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D002986:Clinical Trials as Topic / Q000379:methods; D006801:Humans; D007097:Imines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013927:Thrombosis / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D016896:Treatment Outcome; D010975:Platelet Aggregation Inhibitors
C540445:E 5555; D007097:Imines; D007783:Lactones; D011725:Pyridines; C530299:vorapaxar; D010975:Platelet Aggregation Inhibitors