Platelet GPIb complex as a target for anti-thrombotic drug development

Thromb Haemost. 2008 Mar;99(3):473-9. doi: 10.1160/TH07-12-0718.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aurintricarboxylic Acid / pharmacology
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Disease Models, Animal
  • Drug Design*
  • Fibrinolytic Agents / pharmacology*
  • Fibrinolytic Agents / therapeutic use
  • Hemostasis / drug effects*
  • Humans
  • Membrane Proteins / pharmacology
  • Mice
  • Mice, Knockout
  • Peptides / pharmacology
  • Platelet Glycoprotein GPIb-IX Complex / antagonists & inhibitors*
  • Platelet Glycoprotein GPIb-IX Complex / genetics
  • Platelet Glycoprotein GPIb-IX Complex / metabolism
  • Structure-Activity Relationship
  • Thrombosis / blood
  • Thrombosis / drug therapy*
  • Thrombosis / metabolism
  • von Willebrand Factor / metabolism


  • Fibrinolytic Agents
  • Membrane Proteins
  • Peptides
  • Platelet Glycoprotein GPIb-IX Complex
  • von Willebrand Factor
  • Aurintricarboxylic Acid