title: Approval of the first protease-activated receptor antagonist: Rationale, development, significance, and considerations of a novel anti-platelet agent.
abstract: Twenty-three years after the discovery of the first thrombin receptor, now known as protease-activated receptor 1 (PAR1), the first drug targeting this receptor is available for human use. The PAR1 inhibitor, vorapaxar (Zontivity, MSD), was recently approved by the FDA for use in the USA for the prevention of thrombotic cardiovascular events in patients with a history of myocardial infarction or peripheral artery disease. In this review, we detail the rationale, development, as well as the clinical significance and considerations of vorapaxar, the original PAR antagonist and the latest anti-platelet agent in the pharmaco-armoury against arterial thrombosis.
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia; Department of Clinical Haematology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Shauna L
authors.initials: SL
authors.lastname: French
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia; Department of Clinical Haematology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Jane F
authors.initials: JF
authors.lastname: Arthur
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia; Department of Clinical Haematology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Huyen A
authors.initials: HA
authors.lastname: Tran
authors.affiliation: Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia; Department of Clinical Haematology, Monash University, Melbourne, Victoria, Australia. Electronic address: Justin.Hamilton@monash.edu.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Hamilton
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D017277:Drug Approval; D006801:Humans; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C530299:vorapaxar
keywords: Antiplatelet agents; Arterial thrombosis; Platelets; Protease-activated receptors; Thrombin