Novel Antiplatelet Therapies for Atherothrombotic Diseases

Figures

• 

  Figure 1.. Commonly used and approved antiplatelet drugs and their targets. Platelet activation and aggregation occur through a complex interplay involving several platelet receptors and their ligands. Platelet adhesion initially occurs through interactions between GP (glycoprotein) Ib and von Willebrand factor, and GP VI and subendothelial collagen. Platelet activation additionally occurs through interactions of soluble agonists, such as TXA2 (thromboxane A2), and ADP which binds the P2Y12 receptor, promoting platelet aggregation. Intracellular signaling leads to conformation changes and activation of the GP IIb/IIIa receptor, enhancing its affinity for its major ligand, fibrinogen, which allows linking of platelets. The drugs depicted interrupt these pathways to provide antiplatelet activity. COX indicates cyclooxygenase; and PAR, protease activating receptor.

• 

  Figure 2.. Novel and emerging antiplatelet therapies and their targets. Several additional platelet receptors and pathways have been identified as possible drug targets with the goal of maintaining anti-platelet efficacy while minimizing bleeding risk. Among these are inhibitors of PI3KB (phosphatidylinositol 3 kinase B), a lipid kinase which functions in downstream signaling pathways to mediate platelet activation and thrombus propagation. Additionally, targets include PDI (protein disulfide-isomerase), novel GP (glycoprotein) IIb/IIIa inhibitors, PAR (protease activating receptor)-4 antagonists, P2Y1 inhibitors, and inhibitors of GP Ib and GP VI mediated pathways. Ap4A indicates diadenosine tetraphosphate; and COX, cyclooxygenase.