Sivelestat sodium is a competitive inhibitor of human neutrophil elastase (IC50 = 44 nM; Ki=200 nM); also inhibits leukocyte elastase obtained from rabbit, rat, hamster and mouse.
Sivelestat (EI546) sodium tetrahydrate is a competitive inhibitor of human neutrophil elastase, with an IC50 of 44 nM and a Ki of 200 nM.This compound is under investigation for its potential use in the treatment of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) or disseminated intravascular coagulation (DIC), particularly in the context of COVID-19[1].[2].[3].[4].
体内研究
When administered intratracheally at dosages ranging from 0.021 to 2.1 mg/kg, Sivelestat significantly suppresses lung hemorrhage in hamsters (ID50 = 82 pg/kg) and reduces the increase of skin capillary permeability in guinea pigs (ID50 = 9.6 mg/kg), both of which are induced by human neutrophil elastase[1].
Additionally, the compound, when infused via the tail vein at a dose of 10 mg/kg, has been shown to ameliorate lung injury following hemorrhagic shock in rats[2].
Furthermore, at doses of 15 and 60 mg/kg administered intraperitoneally, Sivelestat effectively prevents ischemia-reperfusion injury in the rat bladder[3].
体外研究
Sivelestat (also known as ONO-5046) does not inhibit a range of other proteases including trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin, and cathepsin G, even at concentrations as high as 100 μM[1].
Sivelestat exhibits IC50 values ranging from 19 nM to 49 nM against neutrophil elastase derived from various species including humans, rabbits, rats, hamsters, and mice, indicating its broad efficacy across species[1].
作用机制
Sivelestat sodium tetrahydrate is an intravenously active NE inhibitor that competitively binds to the target substrate of NE.
搜索
