PAR Antagonists

• Alexander JH, Lopes RD, James S et al (2011) Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 365(8):699–708

  Article  CAS  PubMed  Google Scholar 

• Angiolillo DJ, Capodanno D, Goto S (2010) Platelet thrombin receptor antagonism and atherothrombosis. Eur Heart J 31(1):17–28

  Article  CAS  PubMed  Google Scholar 

• Arora P, Ricks TK, Trejo J (2007) Protease-activated receptor signalling, endocytic sorting and dysregulation in cancer. J Cell Sci 120(Pt 6):921–928

  Article  CAS  PubMed  Google Scholar 

• Becker RC, Moliterno DJ, Jennings LK et al (2009) Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study. Lancet 373(9667):919–928

  Article  CAS  PubMed  Google Scholar 

• Bohula EA, Aylward PE, Bonaca MP et al (2015) Efficacy and safety of vorapaxar with and without a thienopyridine for secondary prevention in patients with previous myocardial infarction and no history of stroke or transient ischemic attack: results from TRA 2°P-TIMI 50. Circulation 132(20):1871–1879

  CAS  PubMed  Google Scholar 

• Bonaca MP, Scirica BM, Creager MA et al (2013) Vorapaxar in patients with peripheral artery disease: results from TRA2°P-TIMI 50. Circulation 127(14):1522–1529

  Article  CAS  PubMed  Google Scholar 

• Bonaca MP, Scirica BM, Braunwald E et al (2014) Coronary stent thrombosis with vorapaxar versus placebo: results from the TRA 2°P-TIMI 50 trial. J Am Coll Cardiol 64(22):2309–2317

  Article  CAS  PubMed  Google Scholar 

• Chackalamannil S, Xia Y, Greenlee WJ et al (2005) Discovery of potent orally active thrombin receptor (protease activated receptor 1) antagonists as novel antithrombotic agents. J Med Chem 48(19):5884–5887

  Article  CAS  PubMed  Google Scholar 

• Chen J, Ishii M, Wang L, Ishii K, Coughlin SR (1994) Thrombin receptor activation. Confirmation of the intramolecular tethered liganding hypothesis and discovery of an alternative intermolecular liganding mode. J Biol Chem 269(23):16041–16045

  CAS  PubMed  Google Scholar 

• Chintala M, Strony J, Yang B, Kurowski S, Li Q (2010) SCH 602539, a protease-activated receptor-1 antagonist, inhibits thrombosis alone and in combination with cangrelor in a Folts model of arterial thrombosis in cynomolgus monkeys. Arterioscler Thromb Vasc Biol 30(11):2143–2149

  Article  CAS  PubMed  Google Scholar 

• Cornelissen I, Palmer D, David T et al (2010) Roles and interactions among protease-activated receptors and P2ry12 in hemostasis and thrombosis. Proc Natl Acad Sci USA 107(43):18605–18610

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Coughlin SR (2000) Thrombin signalling and protease-activated receptors. Nature 407(6801):258–264

  Article  CAS  PubMed  Google Scholar 

• Coughlin SR (2005) Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost 3(8):1800–1814

  Article  CAS  PubMed  Google Scholar 

• Dutta P, Courties G, Wei Y et al (2012) Myocardial infarction accelerates atherosclerosis. Nature 487(7407):325–329

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Farndale RW, Sixma JJ, Barnes MJ, de Groot PG (2004) The role of collagen in thrombosis and hemostasis. J Thromb Haemost 2(4):561–573

  Article  CAS  PubMed  Google Scholar 

• Gilchrist I, Bonaca MP, Scirica BM et al (2015) Vorapaxar and peripheral revascularization: insights from the TRA2P-TIMI 50 trial. J Am Coll Cardiol 65 (10_S) (15):S0735–1097

  Google Scholar 

• Goto S, Yamaguchi T, Ikeda Y, Kato K, Yamaguchi H, Jensen P (2010) Safety and exploratory efficacy of the novel thrombin receptor (PAR-1) antagonist SCH530348 for non-ST-segment elevation acute coronary syndrome. J Atheroscler Thromb 17(2):156–164

  Article  CAS  PubMed  Google Scholar 

• Gurbel PA, Bliden KP, Turner SE et al (2015) Cell-penetrating pepducin therapy targeting PAR1 in subjects with coronary artery disease. Arterioscler Thromb Vasc Biol doi:10.1161/atvbaha.115.931306777

• Hamilton JR, Cornelissen I, Coughlin SR (2004) Impaired hemostasis and protection against thrombosis in protease-activated receptor 4-deficient mice is due to lack of thrombin signaling in platelets. J Thromb Haemost 2(8):1429–1435

  Article  CAS  PubMed  Google Scholar 

• Jennings LK (2009) Mechanisms of platelet activation: need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost 102(2):248–257

  CAS  PubMed  Google Scholar 

• Judge HM, Jennings LK, Moliterno DJ et al (2015) PAR1 antagonists inhibit thrombin-induced platelet activation whilst leaving the PAR4-mediated response intact. Platelets 26(3):236–242

  Article  CAS  PubMed  Google Scholar 

• Kosoglou T, Reyderman L, Tiessen RG et al (2012) Pharmacodynamics and pharmacokinetics of the novel PAR-1 antagonist vorapaxar (formerly SCH 530348) in healthy subjects. Eur J Clin Pharmacol 68(3):249–258

  Article  CAS  PubMed  Google Scholar 

• Macfarlane SR, Seatter MJ, Kanke T, Hunter GD, Plevin R (2001) Proteinase-activated receptors. Pharmacol Rev 53(2):245–282

  CAS  PubMed  Google Scholar 

• Magnani G, Bonaca MP, Braunwald E et al (2015) Efficacy and safety of vorapaxar as approved for clinical use in the United States. J Am Heart Assoc 4(3):e001505

  Article  PubMed  PubMed Central  Google Scholar 

• Mega JL, Braunwald E, Wiviott SD et al (2012) Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 366(1):9–19

  Article  CAS  PubMed  Google Scholar 

• O’Donoghue ML, Bhatt DL, Wiviott SD et al (2011) Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the lessons from antagonizing the cellular effects of thrombin-acute coronary syndromes trial. Circulation 123(17):1843–1853

  Article  PubMed  Google Scholar 

• O'Callaghan K, Kuliopulos A, Covic L (2012) Turning receptors on and off with intracellular pepducins: new insights into G-protein-coupled receptor drug development. J Biol Chem 287(16):12787–12796

  Article  PubMed  PubMed Central  Google Scholar 

• Roberts DE, McNicol A, Bose R (2004) Mechanism of collagen activation in human platelets. J Biol Chem 279(19):19421–19430

  Article  CAS  PubMed  Google Scholar 

• Rooke TW, Hirsch AT, Misra S et al (2011) ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 124(18):2020–2045

  Article  Google Scholar 

• Scirica BM, Bonaca MP, Braunwald E et al (2012) Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2 degrees P-TIMI 50 trial. Lancet 380(9850):1317–1324

  Article  CAS  PubMed  Google Scholar 

• Shinohara Y, Goto S, Doi M, Jensen P (2012) Safety of the novel protease-activated receptor-1 antagonist vorapaxar in Japanese patients with a history of ischemic stroke. J Stroke Cerebrovasc Dis 21(4):318–324

  Article  PubMed  Google Scholar 

• Storey RF, Kotha J, Smyth SS et al (2014) Effects of vorapaxar on platelet reactivity and biomarker expression in non-ST-elevation acute coronary syndromes. The TRACER pharmacodynamic substudy. Thromb Haemost 111(5):883–891

  Article  CAS  PubMed  Google Scholar 

• Trejo J, Hammes SR, Coughlin SR (1998) Termination of signaling by protease-activated receptor-1 is linked to lysosomal sorting. Proc Natl Acad Sci USA 95(23):13698–13702

  Article  CAS  PubMed  PubMed Central  Google Scholar 

• Tricoci P, Huang Z, Held C et al (2012) Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 366(1):20–33

  Google Scholar 

• Tricoci P, Lokhnygina Y, Huang Z et al (2014) Vorapaxar with or without clopidogrel after non-ST-segment elevation acute coronary syndromes: results from the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome trial. Am Heart J 168(6):869–877

  Article  CAS  PubMed  Google Scholar 

• Vandendries ER, Hamilton JR, Coughlin SR, Furie B, Furie BC (2007) Par4 is required for platelet thrombus propagation but not fibrin generation in a mouse model of thrombosis. Proc Natl Acad Sci USA 104(1):288–292

  Article  CAS  PubMed  Google Scholar 

• Whellan DJ, Tricoci P, Chen E et al (2014) Vorapaxar in acute coronary syndrome patients undergoing coronary artery bypass graft surgery: subgroup analysis from the TRACER trial (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome). J Am Coll Cardiol 63(11):1048–1057

  Article  CAS  PubMed  Google Scholar 

• Wiviott SD, Flather MD, O’Donoghue ML et al (2011) Randomized trial of atopaxar in the treatment of patients with coronary artery disease: the lessons from antagonizing the cellular effect of thrombin-coronary artery disease trial. Circulation 123(17):1854–1863

  Article  CAS  PubMed  Google Scholar 

• Zhang C, Srinivasan Y, Arlow DH et al (2012) High-resolution crystal structure of human protease-activated receptor 1. Nature 492(7429):387–392

  Article  CAS  PubMed  PubMed Central  Google Scholar 

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