| Identification | Back Directory | [Name]
Cyclo[L-alanyl-L-seryl-L-isoleucyl-L-prolyl-L-prolyl-L-glutaminyl-L-lysyl-L-tyrosyl-D-prolyl-L-prolyl-(2S)-2-aminodecanoyl-L-α-glutamyl-L-threonyl] (9CI) | [CAS]
906547-89-5 | [Synonyms]
POL6014
Lonodelestat
Cyclo[L-alanyl-L-seryl-L-isoleucyl-L-prolyl-L-prolyl-L-glutaminyl-L-lysyl-L-tyrosyl-D-prolyl-L-prolyl-(2S)-2-aminodecanoyl-L-α-glutamyl-L-threonyl] (9CI) | [Molecular Formula]
C71H111N15O19 | [MOL File]
906547-89-5.mol | [Molecular Weight]
1478.73 |
| Chemical Properties | Back Directory | [Boiling point ]
1750.2±65.0 °C(Predicted) | [density ]
1.36±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
4.46±0.10(Predicted) | [color ]
White to off-white | [Sequence]
cyclo({Aca}-Glu-Thr-Ala-Ser-Ile-Pro-{d-Pro}-{(2S)-2-aminodecanoyl}-Gln-Lys-Tyr-Pro-Pro) |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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].
| Animal Model: | Ten-week-old male C57BL/6j mice[1]. | | Dosage: | 0.05, 0.2, 0.5 and 5 mg/kg. | | Administration: | Administered intranasally (i.n.) 15 minutes before HNE (30 UI, i.n.). | | Result: | Reduced the inflammatory processes of ALI in HNE treated mice. |
| [References]
[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. DOI:10.1016/j.jcf.2019.08.020 |
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