Thrombin receptor antagonists as novel therapeutic targets

Current Opinion in Drug Discovery and Development

Volumn 4, Issue 4, 2001, Pages 417-427

  Chackalamannil, S ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Factor Xa; PAR 1 antagonist; Proteinase activated receptor; Tethered ligand; Thrombin; Thrombin receptor antagonist; TRAP

Indexed keywords

ABCIXIMAB; ACETYLSALICYLIC ACID; ANTIINFLAMMATORY AGENT; ANTITHROMBOCYTIC AGENT; BLOOD CLOTTING FACTOR 10A INHIBITOR; CLOPIDOGREL; COUMARIN; EPTIFIBATIDE; ERYLOSIDE; FIBRINOGEN RECEPTOR ANTAGONIST; FR 171113; HEPARIN DERIVATIVE; HIMBACINE; HIRUDIN DERIVATIVE; PROTEINASE ACTIVATED RECEPTOR 1; PROTEINASE ACTIVATED RECEPTOR 2; PROTEINASE ACTIVATED RECEPTOR 3; RWJ 58259; THROMBIN INHIBITOR; THROMBIN RECEPTOR; UNCLASSIFIED DRUG;

ARTERY THROMBOSIS; ATHEROSCLEROSIS; BLOOD CLOTTING; CLINICAL TRIAL; HEMOSTASIS; HUMAN; PROTEIN DEGRADATION; RECEPTOR INTRINSIC ACTIVITY; RECEPTOR UPREGULATION; RESTENOSIS; REVIEW;

ANIMALS; CARDIOVASCULAR DISEASES; FIBRINOLYTIC AGENTS; HUMANS; RECEPTORS, THROMBIN;

EID: 0034911285     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (87)

1. Overview of hemostasis
2. Coagulation cascade: An overview
3. The coagulation cascade: Initiation, maintenance and regulation
4. Molecular and cellular biology of blood coagulation
5. Big rigs in blood coagulation
6. Coagulation factors and their inhibitors
7. Tissue factor pathway inhibitor and the revised theory of coagulation
8. Cellular effects of thrombin: Pharmacology of the receptor(s) in various cell types and possible development of receptor antagonists
9. Thrombin-cellular interactions
10. The formation of the hemostatic plug - A special case of platelet aggregation. An experiment and a survey of the literature
11. Formation and regulation of platelet and fibrin hemostatic plug
12. Platelet dense granules: Structure, function and implications for hemostasis
13. Pathogenesis of thrombosis
14. Stroke: Antithrombin versus antiplatelet therapy
15. Protease activated receptors in inflammation, neuronal signaling and pain
16. Thrombin receptor overexpression in malignant and physiological invasion process
17. Structure and function of thrombin receptors
18. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation
19. How the protease thrombin talks to cells
20. Thrombin-induced events in non-platelet cells are mediated by the unique proteolytic mechanism established for the cloned platelet thrombin receptor
21. Domains specifying thrombin-receptor interaction
22. Characterization of a functional thrombin receptor. Issues and opportunities
23. Protease-mediated signaling: New paradigms for cell regulation and drug development
24. Mechanism of thrombin receptor agonist specificity. Chimeric receptors and complementary mutations identify an agonist recognition site
25. Protease activated receptor: Theme and variations
26. 2, in rat vascular and gastric smooth muscle
27. Protease activated receptor 3 is a second thrombin receptor in humans
28. Cloning and characterization of human protease-activated receptor-4
29. Thrombin receptor function and cardiovascular disease
30. Thrombin receptor: A novel target for antiplatelet drug development
31. Thrombin receptor antagonists: A work in progress
32. Issues in the development of thrombin receptor antagonists
33. Atherosclerotic plaque rupture and thrombosis. Evolving concepts
34. An antibody against the exosite of the cloned thrombin receptor inhibits experimental arterial thrombosis in the African green monkey
35. Effects of thrombin inhibition on the development of acute platelet thrombus deposition during angioplasty in pigs. Heparin versus recombinant hirudin, a specific thrombin inhibitor
36. Thrombin hypothesis of thrombus generation and vascular lesion formation
37. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor
38. Thrombin activates NF-κB through thrombin receptor and results in proliferation of vascular smooth muscle cells: Role of thrombin in atherosclerosis and restenosis
39. New trends in the interventional treatment of ischaemic heart disease
40. Devices for endovascular abdominal aortic aneurysm repair
41. Role of thrombin receptor in restenosis and atherosclerosis
42. Prevention of platelet-rich arterial thrombosis by selective thrombin inhibition
43. Prolonged thrombin inhibition reduces restenosis after balloon angioplasty in porcine coronary arteries
44. Biochemical and pharmacological properties of clopidogrel: A new ADP receptor antagonist
45. Clopidogrel: A review of its mechanism of action
46. Clopidogrel for prevention of major cardiac events after coronary stent implantation: 30-Day and 6-month results in patients with smaller stents
47. Hirudin interruption of heparin-resistant arterial thrombus formation in baboons
48. Fibrin monomer protects thrombin from inactivation by heparin antithrombin III: Implications for heparin efficacy
49. Clotbound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors
50. Phamacologic aspects of the development of selective thrombin inhibitors as anticoagulants
51. Hirudin as an inhibitor of thrombin
52. Design and characterization of hirulogs: A novel class of bivalent peptide inhibitors of thrombin
53. Recombinant hirudin for unstable angina pectoris: A multicenter, randomized angiographic trial
54. Synthetic low molecular weight thrombin inhibitors: Molecular design and pharmacological profile
55. Advances in the development of thrombin inhibitors
56. Thrombin active site inhibitors
57. Factor Xa inhibitors - A review of the recent patent literature
58. The design and synthesis of noncovalent factor Xa inhibitors
59. Protease activated receptor 1 is the primary mediator of thrombin-stimulated platelet procoagulant activity
60. Final report on the aspirin component of the ongoing Physicians' Health Study
61. Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs
62. Antithrombotic agents: From RGD to peptide mimetics
63. Platelet glycoprotein IIb-IIIa antagonists as prototypical integrin blockers: Novel parenteral and potential antithrombotic agents
64. Platelet glycoprotein IIb/IIIa antagonists
65. Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists
66. Pharmacokinetics and pharmacodynamics of sibrafiban, an orally administered IIb/IIIa antagonist, in patients with acute coronary syndrome
67. Oral blockade of the platelet glycoprotein IIb/IIIa receptor: Fact or fancy?
68. Thrombin receptors on human platelet. Initial localization and subsequent redistribution during platelet activation
69. Inflammation-coagulation network: Are serine protease receptors the knot?
70. Protease-activated receptors: Sentries for inflammation?
71. Specificity to the thrombin receptor for agonist peptide is defined by its extracellular surface
72. Development of a potent thrombin receptor ligand
73. Tethered ligand agonist peptides. Structural requirements for thrombin receptor activation reveal mechanism of proteolytic unmasking of agonist function
74. Enhancement of thrombin receptor activation by thrombin receptor-derived heptapeptide with parafluorophenylalanine in place of phenylalanine
75. 'Tethered ligand' derived pentapeptide agonists of thrombin receptor: A study of side chain requirements for human platelet activation and GTPase stimulation
76. Development of potent thrombin receptor antagonist peptides
77. Photoactivatable peptides based on BMS-197525: A potent antagonist of the human thrombin receptor (PAR-1)
78. Thrombin receptor antagonists derived from tethered ligand agonist peptides
79. Design, synthesis, and biological characterization of a peptide-mimetic antagonist for a tethered-ligand receptor
80. Discovery and optimization of a novel series of thrombin receptor (PAR-1) antagonists: Potent, selective peptide mimetics based on indole and indazole templates
81. Structure-activity relationships of pyrroloquinazolines as thrombin receptor antagonists
82. Inhibition of cellular action of thrombin by N3-cyclopropyl-7-[[4-(1-methylethyl)phenyl]methyl]-7 H-pyrrolo[3,2-f]quinazoline-1,3,-diamine (SCH 79797), a non-peptide thrombin receptor antagonist
83. In vitro antiplatelet profile of FR171113, a novel non-peptide thrombin receptor antagonist
84. Eryloside F, a novel penasterol disaccharide possessing potent thrombin receptor antagonist activity
85. Discovery of potent, non-peptide thrombin receptor antagonists
86. Discovery of a non-peptide small molecule antagonist of the human platelet thrombin receptor (PAR-1)
87. Total synthesis of (+)-himbacine and (+)-himbeline