Therapeutic applications of serine protease inhibitors

Abstract

Serine proteases (SPs) are known to regulate important biological processes, which makes them attractive targets in therapy. In recent years, much effort has been directed to revealing physiological roles played by some of these enzymes, as well as to identify and characterise various members of the class as potential drug targets. These efforts materialised in the design of new drugs for thrombotic diseases, emphysema, asthma, herpesvirus protease, hepatitis C NS3 protease etc. and in emerging therapies for the treatment of cancer, based on the inhibition of plasminogen-type urokinase. However, some major issues, such as bioavailability, potency and selectivity of the first generation(s) of such inhibitors, must be improved for achieving better therapeutic profiles. This article presents an overview of the major important targets within the SP class, emphasising for each the recent advances in the design of effective SP inhibitors (SPIs) with potential therapeutic applications in a variety of medical fields.

• drug design
• elastase
• enzyme-inhibitor adduct
• Factor Xa (fXa)
• hepatitis C virus protease
• herpesvirus protease
• serine protease inhibitors (SPIs)
• thrombin
• tryptase
• urokinase-type plasminogen activator
• X-ray crystallography