Targeting serine proteases in asthma.
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 non-human species are also discussed.
Guay
Caroline
C
Unité de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Sainte-Foy, Quebec, Canada G1V 4G5.
Laviolette
Michel
M
Tremblay
Guy M
GM
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*
D015842:Serine Proteinase Inhibitors