Lonodelestat  (Synonyms: POL6014)

Lonodelestat (POL6014) is a potent, orally active and selective peptide inhibitor of human neutrophil elastase (hNE). Lonodelestat (POL6014) 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].

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

1478.73

C₇₁H₁₁₁N₁₅O₁₉

906547-89-5

Solid

White to off-white

cyclo[ASIPPQKYPPNle(bu)ET]

Room temperature in continental US; may vary elsewhere.

Sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [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 healthy volunteers and subjects with cystic fibrosis. J Cyst Fibros. 2020 Mar;19(2):299-304.  [Content Brief]