Thrombin inhibitors A new generation of antithrombotics

The activity of thrombin is central to the processes of fibrin generation and platelet aggregation, which are inherent in thrombus formation. As a result of x-ray crystallographic studies over the last 5 years, we now have a firm knowledge of the structural basis for the specific interactions of thrombin with components of the coagulation system. Moreover, the crystal structures of thrombin will assist in the development of specific inhibitors with desired pharmacological properties, such as oral availability. Several inhibitors are already in clinical trials as antithrombotic agents and, although only small studies have been completed to date, the preliminary results are encouraging. Hirudin and Hirulog(™) appear to offer advantages to heparin, the current mainstay of antithrombotic therapy, in several indications including unstable angina, thrombolytic therapy, and coronary angioplasty.