Sivelestat is a cell-permeable sulfanilide compound that acts as a potent, substrate-competitive, and highly specific inhibitor of neutrophil elastase (IC50 = 19-49 nM in rat, rabbit, hamster, human, and mouse leukocyte elastase). Sivelestat displays >100-fold greater selectivity over pancreas elastase (IC50 = 5.6 μM). Sivelestat does not inhibit trypsin, thrombin, plasmin, kallikrein, chymotrypsin, and cathepsin G even at concentrations as high as 100 μM. Sivelestat effectively suppresses human neutrophil elastase-induced lung hemorrhage and skin capillary permeability. Sivelestat is also reported to inhibit mast cell Stat6-protease.
