Sivelestat sodium tetrahydrate (ONO5046 sodium tetrahydrate) is a competitive inhibitor of human neutrophil elastase, with an IC50 of 44 nM and a Ki 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.

Sivelestat (ONO-5046) is not an inhibitor of trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin, or cathepsin G, even at concentrations up to 100 μM[1]. However, it effectively inhibits neutrophil elastase across various species, demonstrating IC50 values of 44 nM (human), 36 nM (rabbit), 19 nM (rat), 37 nM (hamster), and 49 nM (mouse), showcasing its specificity and potential for therapeutic applications[1].

Sivelestat (ONO-5046, 0.021-2.1 mg/kg, intratracheally) suppresses lung hemorrhage in hamsters (ID50 = 82 pg/kg) and increases skin capillary permeability in guinea pigs (ID50 = 9.6 mg/kg) via intravenous administration, both induced by human neutrophil elastase[1]. Additionally, Sivelestat (10 mg/kg, tail vein infusion) ameliorates lung injury after hemorrhagic shock in rats[2], and prevents ischemia-reperfusion injury in the rat bladder (15, 60 mg/kg, ip)[3].