Freselestat quarterhydrate (ONO-6818 quarterhydrate) is a potent and orally activeneutrophilelastaseinhibitor with aK_iof 12.2 nM. Freselestat quarterhydrate is >100-fold less-active against other proteases such as trypsin, protein-ase 3, pancreaticelastase, plasmin,thrombin, collagenase,cathepsinG, and murine macrophageelastase. Freselestat quarterhydrate has a potent anti-inflammatory activity^[1][2][3][4].

Ki: 12.2 nM (Neutrophil elastase)^[3]

Simulated extracorporeal circulation is established by recirculating fresh heparinized (3.75 U/mL) human blood for 120 minutes in a membrane oxygenator and a roller pump with and without 1.0 μM of Freselestat (ONO-6818). Neutrophil elastase levels are significantly lower in the Freselestat group. Freselestat significantly reduces interleukin 8 and C5b-9 production. Freselestat does not modulate changes of CD11b and L-selectin during recirculation^[3].

Freselestat (ONO-6818; 10-100 mg/kg; oral administration; daily; for 8 weeks) treatment attenuates dose-dependently HNE-induced increases in lung myeloperoxidase activity, hemoglobin, and neutrophil count in bronchoalveolar lavage fluid. ONO-6818 inhibits acute lung injury induced by HNE by minimizing lung hemorrhage and accumulation of neutrophils in the lung^[1].

457.03

Solid

C₂₃H₂₈N₆O₄.1/4H₂O

Room temperature in continental US; may vary elsewhere.