Therapeutic applications and design of mast cell tryptase inhibitors

In recent years, a role for the mast cell has emerged as a multifunctional, key effector cell in the immune system and may also serve to modulate the inflammatory response and immune-nervous system interactions. Mast cell stimulation leads to the secretion of several classes of mediators including proteolytic enzymes, most notably the trypsin-like serine proteinase, tryptase. Recent immunological and biological studies have demonstrated an association of mast cells and tryptase activity with a broad range of allergic and inflammatory conditions affecting nearly all the major systems of the human body. At present, there is sufficient evidence to strongly suggest that tryptase activity is a key aspect of some common and serious allergic and inflammatory diseases, particularly asthma. Due to the increasing prevalence of asthma in industrialized society, the inhibition of tryptase is viewed as a potentially important and novel therapeutic mechanism for disease intervention. Recent advances in the design of potent and selective inhibitors of tryptase provide a great deal of promise for the development of safe and effective drugs for the treatment of asthma and possibly a range of other diseases in the early 21st century.