Sivelestat is a competitive inhibitor of human neutrophil elastase(IC50 = 44 nM and Ki=200 nM) and also inhibits leukocyte elastase obtained from rabbit, rat, hamster and mouse.
Human neutrophil elastase (HNE) is a protease that participates in tissue injuries of emphysema, rheumatoid arthritis, and septic shock. Sivelestat is a potent, selective, intravenously active HNE inhibitor with an IC50 value of 44±3nM and a Ki value of 200±20nM. It also inhibited leukocyte elastase obtained from rabbits, rats, hamsters, and mice with IC50 values of 36±1, 19±1, 37±4, and 49±5nM, respectively. Sivelestat inhibited porcine pancreas elastase with an IC50 value of 5.6±0.2μM. Intratracheal administration of sivelestat dose-dependently suppressed lung hemorrhage in hamsters with an ID50 value of 82μg/kg. In Guinea pigs, intravenous administration of sivelestat significantly and dose-dependently suppressed HNE-induced increase in skin capillary permeability with an ID50 value of 9.6mg/kg[3]. In rats, intravenous injection of sivelestat at a dosage of 10mg/kg significantly ameliorated lung injury induced by hemorrhagic shock followed by resuscitation[4].
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