Platelet GPIb complex as a target for anti-thrombotic drug development.
Specific inhibition of platelet function is a major target of anti-thrombotic drug research. Platelet receptors are both accessible and specific but have multiple functions often linked to a wide range of ligands. GPIb complex is best known as a major platelet receptor for von Willebrand factor essential for platelet adhesion under high shear conditions found in arteries and in thrombosis. Recent animal studies have supported inhibition of GPIb as a good candidate for anti-thrombotic drug development with several classes of proteins showing important specific effects and the required discrimination between roles in haemostasis and thrombosis is important to protect against bleeding complications. These include antibodies, several classes of snake venom proteins, mutant thrombin molecules and peptides affecting subunit interactions. However, due to the nature of its receptor-ligand interactions involving large protein-protein interfaces, the possibility of developing classic pharmaceutical inhibitors for long term (and perhaps oral) treatment is still unclear, and additional information about structural interactions and signalling mechanisms is essential.
Clemetson
Kenneth J
KJ
Theodor Kocher Institute, University of Berne, Freiestrasse 1, CH-3012 Berne, Switzerland. clemetson@tki.unibe.ch
Clemetson
Jeannine M
JM
D000818:Animals; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000494:pharmacology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D005343:Fibrinolytic Agents; D008565:Membrane Proteins; D010455:Peptides; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D001312:Aurintricarboxylic Acid