Inhibitors of the interactions between collagen and its receptors on platelets.
At sites of vascular injury, collagen-mediated platelet adhesion and activation have long been known as one of the first events in platelet-dependent thrombus formation. Studying patients with bleeding disorders that are caused by defective platelet adhesion to collagen resulted in the identification of several platelet collagen receptors, with glycoprotein VI and integrin α2β1 being the most important ones. Subsequent development of specific collagen receptor knockout mice and various inhibitors of platelet binding to collagen have further proven the role of these receptors in haemostasis and thrombosis. The search for clinically applicable inhibitors for use as antithrombotic drug has led to the identification of inhibitory antibodies, soluble receptor fragments, peptides, collagen-mimetics and proteins from snake venoms or haematophagous animals. In experimental settings, these inhibitors have a good antithrombotic effect, with little prolongation of bleeding times, suggesting a larger therapeutic window than currently available antiplatelet drugs. However, at present, none of the collagen receptor blockers are in clinical development yet.
Laboratory for Thrombosis Research, KU Leuven campus Kortrijk, Kortrijk, Belgium. Hans.Deckmyn@kuleuven-kortrijk.be
Hans
H
Deckmyn
Simon F
SF
De Meyer
Katleen
K
Broos
Karen
K
Vanhoorelbeke
D000595:Amino Acid Sequence; D000818:Animals; D003094:Collagen / Q000037:antagonists & inhibitors*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D008969:Molecular Sequence Data; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000502:physiology; D013927:Thrombosis / Q000188:drug therapy
D038982:Integrin alpha2beta1; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; C098341:platelet membrane glycoprotein VI; D003094:Collagen