Freselestat quarterhydrate  (Synonyms: ONO-6818 quarterhydrate; ONO-PO-736 quarterhydrate)

Freselestat quarterhydrate (ONO-6818 quarterhydrate) is a potent and orally active neutrophil elastase inhibitor with a K_i of 12.2 nM. Freselestat quarterhydrate is >100-fold less-active against other proteases such as trypsin, protein-ase 3, pancreatic elastase, plasmin, thrombin, collagenase, cathepsin G, and murine macrophage elastase. 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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

457.03

C₂₃H₂₈N₆O₄.1/4H₂O

固体

White to off-white

Room temperature in continental US; may vary elsewhere.

• [1]. Am J Respir Crit Care Med. 2002 Aug 15;166(4):496-500.  [Content Brief]

  [2]. K Ohmoto, et al. Design and synthesis of new orally active inhibitors of human neutrophil elastase. Bioorg Med Chem. 2001 May;9(5):1307-23.  [Content Brief]

  [3]. Yasushi Hirota, et al. Effects of the neutrophil elastase inhibitor (ONO-6818) on acetic acid induced colitis in Syrian hamsters. J Vet Med Sci. 2004 Oct;66(10):1223-8.  [Content Brief]

  [4]. Yukihiro Yoshimura, et al. ONO-6818, a novel, potent neutrophil elastase inhibitor, reduces inflammatory mediators during simulated extracorporeal circulation. Ann Thorac Surg. 2003 Oct;76(4):1234-9.  [Content Brief]