Sivelestat (sodium tetrahydrate)

Sivelestat (EI546) sodium tetrahydrate is a competitive inhibitor of human neutrophil elastase, with an IC₅₀ of 44 nM and a K_i of 200 nM. Sivelestat (EI546) sodium tetrahydrate has the potential for the study of acute lung injury/acute respiratory distress syndrome or disseminated intravascular coagulation in COVID-19^[1][2][3][4]. In Vitro: Sivelestat (ONO-5046) does not inhibit trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin and cathepsin G even at 100 μM^[1].
Sivelestat (ONO-5046) exhibits IC₅₀ values of 44 nM, 36 nM, 19 nM, 37 nM and 49 nM for human, rabbit, rat, hamster and mouse neutrophil elastase, respectively^[1].
In Vivo: Sivelestat (ONO-5046, 0.021-2.1 mg/kg, intratracheally) suppresses lung hemorrhage in hamster (ID₅₀ = 82 pg/kg) by intratracheal administration and increase of skin capillary permeability in guinea pig (ID₅₀ = 9.6 mg/kg) by intravenous administration, both of which are induced by human neutrophil elastase^[1].
Sivelestat (10 mg/kg, infusion via the tail vein) ameliorates lung injury after hemorrhagic shock in rats^[2].
Sivelestat (15, 60 mg/kg, ip) prevents ischemia–reperfusion injury in the rat bladder^[3].