125
Views
19
CrossRef citations to date
0
Altmetric
Review

Mechanism of action and clinical development of platelet thrombin receptor antagonists

, &
Pages 1191-1200 | Published online: 10 Jan 2014

References

  • Davi G, Patrono C. Platelet activation and atherothrombosis. N. Engl. J. Med.357(24), 2482–2494 (2007).
  • Angiolillo DJ, Ueno M, Goto S. Basic principles of platelet biology and clinical implications. Circ. J.74(4), 597–607 (2010).
  • Chen ZM, Jiang LX, Chen YP et al. Addition of clopidogrel to aspirin in 45852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet366(9497), 1607–1621 (2005).
  • Sabatine MS, Cannon CP, Gibson CM et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N. Engl. J. Med.352(12), 1179–1189 (2005).
  • Wiviott SD, Braunwald E, McCabe CH et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N. Engl. J. Med.357(20), 2001–2015 (2007).
  • Yusuf S, Zhao F, Mehta SR et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N. Engl. J. Med.345(7), 494–502 (2001).
  • Wallentin L, Becker RC, Budaj A et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N. Engl. J. Med.361(11), 1045–1057 (2009).
  • Steinhubl SR, Berger PB, Mann JT et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA288(19), 2411–2420 (2002).
  • Brummel KE, Paradis SG, Butenas S et al. Thrombin functions during tissue factor-induced blood coagulation. Blood100(1), 148–152 (2002).
  • Davey MG, Lüscher EF. Actions of thrombin and other coagulant and proteolytic enzymes on blood platelets. Nature216(5118), 857–858 (1967).
  • Meadows TA, Bhatt DL. Clinical aspects of platelet inhibitors and thrombus formation. Circ. Res.100(9), 1261–1275 (2007).
  • Coughlin SR. How the protease thrombin talks to cells. Proc. Natl Acad. Sci. USA96(20), 11023–11027 (1999).
  • Coughlin SR. Protease-activated receptors in vascular biology. Thromb. Haemost.86(1), 298–307 (2001).
  • Coughlin SR. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J. Thromb. Haemost.3(8), 1800–1814 (2005).
  • Coughlin SR. Thrombin signalling and proteaseactivated receptors. Nature407(6801), 258–264 (2000).
  • Angiolillo DJ, Capodanno D, Goto S. Platelet thrombin receptor antagonism and atherothrombosis. Eur. Heart J.31(1), 17–28 (2010).
  • Al-Ani B, Saifeddine M, Hollenberg MD. Detection of functional receptors for the proteinase-activated receptor-2-activating polypeptide, SLIGRL-NH2, in rat vascular and gastric smooth muscle. Can. J. Physiol. Pharmacol.73(8), 1203–1207 (1995).
  • Ishihara H, Connolly AJ, Zeng D et al. Protease activated receptor-3 is a second thrombin receptor in humans. Nature386(6624), 502–506 (1997).
  • Cupit LD, Schmidt VA, Gnatenko DV, Bahou WF. Expression of protease activated receptor 3 (PAR3) is upregulated by induction of megakaryocyte phenotype in human erythroleukemia (HEL) cells. Exp. Hematol.32(10), 991–999 (2004).
  • Kahn ML, Zheng YW, Huang W et al. A dual thrombin receptor system for platelet activation. Nature394(6694), 690–694 (1998).
  • Nystedt S, Emilsson K, Wahlestedt C, Sundelin J. Molecular cloning of a potential proteinase activated receptor. Proc. Natl Acad. Sci. USA9(20), 9208–9212 (1994).
  • Chackalamannil S. Thrombin receptor (protease activated receptor-1) antagonists as potent antithrombotic agents with strong antiplatelet effects. J. Med. Chem.49(18), 5389–5403 (2006).
  • Shah R. Protease-activated receptors in cardiovascular health and diseases. Am. Heart J.157(2), 253–262 (2009).
  • Xu W-f, Andersen H, Whitmore TE et al. Cloning and characterization of human protease-activated receptor 4. Proc. Natl Acad. Sci. USA95(12), 6642–6646 (1998).
  • Tesfamariam B. Thrombin receptor-mediated vascular relaxation differentiated by a receptor antagonist and desensitization. Am. J. Physiol.267(5 Pt 2), H1962–H1967 (1994).
  • Ku DD, Zaleski JK. Receptor mechanism of thrombin-induced endothelium dependent and endothelium independent coronary vascular effects in dogs. J. Cardiovasc. Pharmacol.22(4), 609–616 (1993).
  • Zimmerman GA, Elstad MR, Lorant DE et al. Platelet-activating factor (PAF): signalling and adhesion in cell–cell interactions. Adv. Exp. Med. Biol.416, 297–304 (1996).
  • Johnson K, Choi Y, DeGroot E, Samuels I, Creasey A, Aarden L. Potential mechanisms for a proinflammatory vascular cytokine response to coagulation activation. J. Immunol.160(10), 5130–5135 (1998).
  • Chintala MS, Chiu PJ, Bernadino V et al. Disparate effects of thrombin receptor activating peptide on platelets and peripheral vasculature in rats. Eur. J. Pharmacol.349(2–3), 237–243 (1998).
  • Chackalamannil S, Xia Y, Greenlee WJ et al. Discovery of potent orally active thrombin receptor (protease activated receptor 1) antagonists as novel antithrombotic agents. J. Med. Chem.48(19), 5884–5887 (2005).
  • Chintala M, Ahn HS, Foster C et al. Antithrombotic effects of SCH 205831: a potent, selective and orally active antagonist of the PAR-1 thrombin receptor. J. Thromb. Haemost.3(Suppl. 1), 286 (2005).
  • Chintala M, Kurowski S, Vemulapalli S et al. Efficacy of SCH 602539, a selective thrombin receptor antagonist alone and in combination with cangrelor in a Folts model of thrombosis in anesthetized monkeys. Eur. Heart J.28(Suppl. 1), 188 (2007).
  • Chackalamannil S, Wang Y, Greenlee WJ et al. Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activity. J. Med. Chem.51(11), 3061–3064 (2008).
  • Chintala M, Vemulapalli S, Kurowski S et al. SCH 530348, a novel oral antiplatelet agent, demonstrated no bleeding risk alone or in combination with aspirin and clopidogrel in cynomolgus monkeys. Arterioscl. Thromb. Vasc. Biol.28, e138–e139 (2008).
  • Chackalamannil S, Davies RJ, Asberom T Doller D, Leone D. A highly efficient total synthesis of (+)-himbacine. J. Am. Chem. Soc.40(118), 9812–9813 (1996).
  • Doller D, Chackalamannil S, Czarniecki M, McQuade R, Ruperto V. Design, synthesis, and structure-activity relationship studies of himbacine derived muscarinic receptor antagonists. Bioorg. Med. Chem. Lett.9(6), 901–906 (1999).
  • The TRACER Exective and Steering Committees. The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial: study design and rationale. Am. Heart J.158(3), 327–334 (2009).
  • Morrow DA, Scirica BM, Fox KA et al. Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA2P)-TIMI 50 trial. Am. Heart J.158(3), 335–341 (2009).
  • Oestreich J. SCH-530348, a thrombin receptor (PAR-1) antagonist for the prevention and treatment of atherothrombosis. Curr. Opin. Invest. Drugs10(9), 988–996 (2009).
  • Kosoglou T, Reydeman L, Fales RR et al. Pharmacodynamics, and pharmacokinetics of novel protease-activated receptor antagonist SCH 530348. Circulation112(Suppl.), 32 (2005).
  • Kosoglou T, Tiessen R, Van Vliet AA, Fales RR, Keller R, Cutler DL. Safety and tolerability of SCH 530348, a novel antiplatelet agent, after single and multiple oral dosing in healthy subjects. Eur. Heart J.29(Suppl.), 201, P1340 (2008).
  • Reyderman L, Kosoglou T, Kasserra C et al. Lack of ethnic differences in the pharmacodynamics (PD) and pharmacokinetics (PK) of SCH 530348, a novel oral antiplatelet agent, in Japanese and Caucasian subjects. Clin. Pharmacol. Ther.85(Suppl. 1), S21, PI-41 (2009).
  • Kosoglou T, Reyderman L, Kasserra C et al. Optimizing dose of the novel thrombin receptor antagonist SCH 530348 based on pharmacodynamics and pharmacokinetics in healthy subjects. Clin. Pharmacol. Ther.83(Suppl. 1), S55 (2008).
  • Becker RC, Moliterno DJ, Jennings LK et al. Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled Phase II study. Lancet373(9667), 919–928 (2009).
  • Jennings LK, Earhart A, Becker RC, Reyderman L, Veltri E, Harrington RA. Thrombin receptor antagonist (TRA; SCH530348) is a selective, potent inhibitor of PAR1 activity with predictable pharmacokinetics. Presented at: American Heart Association Scientific Sessions. Orlando, FL, USA, 4–7 November 2007.
  • Goto S, Yamaguchi T, Ikeda Y, Kato K, Yamaguchi H, Jensen P. Phase II trial of the novel antiplatelet agent, SCH 530348, in Japanese patients with non-ST segment elevation acute coronary syndromes (NSTE ACS). Eur. Heart J.29(Suppl.), 829, P4767 (2008).
  • Shinohara Y, Goto S, Shimizu K, Jensen P. A Phase II safety study of novel antiplatelet agent, SCH 530348, in Japanese patients with prior ischemic stroke. Int. J. Stroke3(Suppl. 1), 139, PO101–PO193 (2008).
  • Serebruany VL, Kogushi M, Dastros-Pitei D Flather M, Bhatt DL. The in vitro effects of E5555, a protease-activated receptor (PAR)-1 antagonist, on platelet biomarkers in healthy volunteers and patients with coronary artery disease. Thromb. Haemost.102(1), 111–119 (2009).
  • Kogushi M, Kobayashi H, Matsuoka T et al. Antithrombotic and bleeding time effects of E5555, an orally active protease-activated receptor-1 antagonist, in guinea pigs. Circulation108(Suppl. IV), 280 (2003).
  • Kai Y, Hirano K, Maeda Y, Nishimura J, Sasaki T, Kanaide H. Prevention of the hypercontractile response to thrombin by proteinase-activated receptor-1 antagonist in subarachnoid hemorrhage. Stroke38(12), 3259–3265 (2007).
  • Kogushi M, Yokohama H, Kitamura S, Hishinuma I. Effects of E5555, a protease activated receptor-1 antagonist, on the inflammatory markers in vitro. J. Thromb. Haemost.5(Suppl.), 059 (2007).
  • Marion A, Reyes J, Chen H, Wittek A. Safety, pharmacokinetics and pharmacodynamics of ascending multiple oral doses of a new protease activated receptor-1 inhibitor in healthy volunteers. Presented at: American College of Clinical Pharmacology 35th Annual Meeting. Cambridge, MA, USA, 17–19 September 2006.
  • Takeuchi M, Kageyama M, Kitamura S, Hagino R, Ozawa H, Tanaka H. Pharmacodynamics and safety of a novel protease activated receptor-1 antagonist E5555 for healthy volunteers. Eur. Heart J.28(Suppl.), 14 (2007).

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.