Sivelestat (EI546) 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.
体外研究
Sivelestat (ONO-5046) does not inhibit trypsin, thrombin, plasmin, plasma kallikrein, pancreas kallikrein, chymotrypsin and cathepsin G even at 100 μM.
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.
体内研究
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.
Sivelestat (10 mg/kg, infusion via the tail vein) ameliorates lung injury after hemorrhagic shock in rats.
Sivelestat (15, 60 mg/kg, ip) prevents ischemia–reperfusion injury in the rat bladder.
Animal Model:
Male Golden hamsters, weighing 90 to 110 g.
Dosage:
0.021-2.1 mg/kg.
Administration:
Intratracheally five min before HNE injection.
Result:
Significantly and dosedependently suppressed the lung hemorrhage.
Animal Model:
Male Sprague-Dawley rats weighing 350-400 g.
Dosage:
10 mg/kg.
Administration:
Continuous infusion via the tail vein at 10 mg/kg/h for 60 min during the resuscitation phase.
Result:
Greatly suppressed lung injury, as revealed by the reduced histological damage.
Significantly ameliorated HSR-induced lung injury.
Markedly decreased the levels of TNF-α and iNOS gene.
Animal Model:
Male Sprague Dawley rats, 8 weeks old and weighing 250-320 g.
Dosage:
15 mg/kg or 60 mg/kg.
Administration:
IP.
Result:
Decreased the blood flow in the bladder during reperfusion phase compared to the IR group.
分子式
C20H29N2NaO11S
分子量
528.51
CAS号
201677-61-4
中文名称
西维来司钠四水合物
运输条件
Room temperature in continental US; may vary elsewhere.