208848-19-5

208848-19-5 structure

Name: ONO 6818
Chemical Name: freselestat
CAS Number: 208848-19-5
Molecular Formula: C₂₃H₂₈N₆O₄
Molecular Weight: 452.50600
Catalog: Signaling Pathways Metabolic Enzyme/Protease Elastase
Create Date: 2017-07-15 22:02:54
Modify Date: 2024-01-20 10:03:50
Freselestat (ONO-6818) is a potent and orally active neutrophil elastase inhibitor with a Ki of 12.2 nM. Freselestat 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 has a potent anti-inflammatory activity[1][2][3][4].

Name	freselestat

Description	Freselestat (ONO-6818) is a potent and orally active neutrophil elastase inhibitor with a Ki of 12.2 nM. Freselestat 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 has a potent anti-inflammatory activity[1][2][3][4].
Related Catalog	Signaling Pathways >> Metabolic Enzyme/Protease >> Elastase Research Areas >> Inflammation/Immunology
Target	Ki: 12.2 nM (Neutrophil elastase)[3]
In Vitro	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].
In Vivo	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]. Animal Model: Male Wistar rats (228 g) induced by human neutrophil elastase (HNE)[1] Dosage: 10 mg/kg, 100 mg/kg Administration: Oral administration; daily; for 8 weeks Result: Attenuated dose-dependently HNE-induced increases in lung myeloperoxidase activity, hemoglobin, and neutrophil count in bronchoalveolar lavage fluid.
References	[1]. Am J Respir Crit Care Med. 2002 Aug 15;166(4):496-500. [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. [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. [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.

Density	1.32g/cm3
Molecular Formula	C₂₃H₂₈N₆O₄
Molecular Weight	452.50600
Exact Mass	452.21700
PSA	146.00000
LogP	3.16880
Index of Refraction	1.633

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