Sivelestat sodium tetrahydrate (CAS 201677-61-4)

Sivelestat sodium tetrahydrate is a competitive inhibitor of human neutrophil elastase (HNE) (IC50 = 44 nM, Ki = 0.2 µM). Sivelestat sodium tetrahydrate also effectively inhibits leukocyte elastase derived from hamster, mouse, rabbit and rat (IC50 = 19 to 49 nM). Sivelestat sodium tetrahydrate, even at concentrations of 100 µM, does not inhibit plasma kallikrein, plasmin, thrombin, trypsin, pancreas kallikrein, chymotrypsin and cathepsin G. In in-vivo studies, sivelestat sodium tetrahydrate suppressed lung hemorrhage in hamster (ID50 = 82 µg/kg) by intratracheal administration and increased skin capillary permeability in guinea pigs (ID50 = 9.6 mg/kg) by intravenous administration, both of which were induced by human neutrophil elastase.

References

Shimoda, M. et al.,, Protective effect of Sivelestat in a porcine hepatectomy model prepared using an intermittent Pringle method. Eur. J. Pharmacol. 587, 248-252, (2008); Maeda, Y. et al.,, Sivelestat Relaxes Porcine Coronary Artery via Inhibition of Ca2+ Sensitization Induced by a Receptor Agonist. J. Cardiovasc. Pharmacol. 51, 476-482, (2008); Kono, T. et al.,, Neutrophil elastase inhibitor, sivelestat sodium hydrate prevents ischemia-reperfusion injury in the rat bladder. Mol. Cell Biochem. 311, 87-92, (2008)