Issues in the development of thrombin receptor antagonists.
The identification of the human thrombin receptor has prompted considerable interest in the development of receptor antagonists that can inhibit the effects of thrombin on cells without affecting fibrin formation. Increasing information about the biology of the receptor highlights some of the potential pitfalls in the development and application of such agents. However, it also provides additional insights into the potential mechanisms by which an antagonist might work beyond the original approach of developing competitive inhibitors of the tethered ligand domain. Thrombin receptors have proved to be present on a variety of cells other than platelets, including other vascular cells and cells within the central nervous system. Although most of the recent emphasis in thinking about the need for anti-thrombin receptor agents has focused on their use as anti-platelet agents, it is worth considering that the best clinical uses of such drugs may ultimately prove to have little to do with platelets.
Brass
L F
LF
Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004705:Endocytosis; D010450:Endopeptidases / Q000502:physiology; D005337:Fibrin / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000502:physiology; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013917:Thrombin / Q000378:metabolism
D008024:Ligands; D018179:Receptors, Thrombin; D005337:Fibrin; D011494:Protein Kinases; D010450:Endopeptidases; D013917:Thrombin; D019204:GTP-Binding Proteins