Targeting Serine Proteases in Asthma

Caroline      Guay; Michel      Laviolette; Guy   M.   Tremblay

doi:10.2174/156802606776287054

Abstract

Leukocytes and lung structural cells contribute to the pathophysiology of asthma through the production of numerous mediators including serine proteases. Such proteases include mast cell tryptase and chymase; neutrophil elastase, cathepsin G and myeloblastin (proteinase 3); bronchial epithelial cell-derived transmembrane protease, serine 11D (human airway trypsin-like protease); cytotoxic T lymphocyte- and natural killer cell-derived granzyme B; and, eosinophil serine protease 1 (testisin). Considerable effort to develop potent and selective inhibitors, mostly non-peptidic, especially targeting tryptase and chymase have been made in the last few years. This review presents promising inhibitors, currently in the research and development pipeline. Some endogenous inhibitors and other compounds purified from nonhuman species are also discussed.

Keywords: Serine protease inhibitors, asthma, tryptase, chymase, leukocyte elastase, inflammation

« Previous