Lonodelestat TFA (POL6014 TFA) is a potent, orally active and selective peptide inhibitor of human neutrophil elastase (hNE). Lonodelestat TFA has the potential for the research of cystic fibrosis (CF)[1][2][3].
Lonodelestat (POL6014) significantly and efficiently reduced the inflammatory processes of ALI in HNE treated mice[1].
Lonodelestat (POL6014, 0.1, 0.5, 2 and 10 mg/kg, intranasally administered) dose-dependently and significantly reduces the number of macrophages, epithelial cells, neutrophils and lymphocytes recovered in BAL. The maximum inhibition was reached at 2 mg/kg in reducing neutrophils by 65% (p<0.001), epithelial cells by 68% (p<0.001), macrophages by 33% (p<0.001) and lymphocytes by 77% (p<0.001)[1].
[1]. Lagente V, et al. A novel Protein Epitope Mimetic (PEM) neutrophil elastase (NE) inhibitor, POL6014, inhibits human NE-induced acute lung injury in mice. ATS, San Diego, May 15-20, 2009.
[2]. Odile Sellier-Kessler, et al. Inhibition of lung inflammation by a protein epitope mimetic (PEM) neutrophil elastase inhibitor, POL6014, in a sub-chronic tobacco smoke (TS) model in mice. European Respiratory Journal 2013 42: 1762.
[3]. Barth P, et al. Single dose escalation studies with inhaled POL6014, a potent novel selective reversible inhibitor of human neutrophil elastase, in healt volunteers and subjects with cystic fibrosis. J Cyst Fibros. 2020 Mar;19(2):299-304.