Small Molecular Drug Discovery and Development An Overview of Antithrombotic Drug Discovery and Development

Antithrombotic drugs include anticoagulants (e.g., warfarin), antiplatelet drugs (e.g, clopidogrel) and thrombolytic agents (such as t-PA). These drugs are used in a wide range of indications for the prevention and treatment of blood clotting related diseases including acute coronary syndromes (ACS) such as heart attack, unstable angina, and myocardial infarction (MI), stroke, venous thromboembolism (VTE), and peripheral arterial occlusion. This review will focus on the issues with the existing oral antiplatelet and anticoagulant drugs and the progress made in the development of improved antithrombotic agents. Both platelet aggregation and blood coagulation pathways are involved in thrombus formation (Fig. 1). In the presence of normal, non-disrupted endothelium, platelets and blood coagulation factors are not activated. However, in response to vessel injury, Von Willebrand’s factor (vWF), collagen and tissue factor (TF) are exposed from endothelium, which contact with blood components and activate platelet adhesion and aggregation, as well as the intrinsic pathway of the coagulation cascade. Activation of coagulation cascade further augments platelet activation which in turn amplifies the coagulation cascade. So blood coagulation and platelet aggregatio