Mutations in ELANE, the gene for neutrophil elastase (NE), a protease expressed early in neutrophil development, are the most frequent cause of cyclic (CyN) and severe congenital neutropenia (SCN)[3]. Alvelestat is an orally bioavailable, affinity and selective inhibitor of neutrophil elastase (NE) with a pIC50 value of 7.9 nM, a Ki value of 9.4 nM and a Kd value of 9.5 nM[4]. Alvelestat (20 μg/mL; 16 hours; HBE and A549 cells) treatment decreases cells death and decreases the levels of IL-1β, IL-6, and TNF-αin vitro[5]. Alvelestat (1 - 10 mg/kg; oral administration; twice daily; for 4 days; female BALB/cJBomTac mice) treatment reduces the inflammatory response to cigarette smoke as indicated by a reduction in BAL neutrophils and interleukin-1βin vivo[4].
Alvelestat/阿尔韦莱司他 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Porcine aortic valve interstitial cells (pVICs)
40 nmol/L
24 hours
To investigate the effects of Alvelestat on inflammation, apoptosis, and calcification in pVICs. Results showed that Alvelestat inhibited osteogenic differentiation, inflammation, and apoptosis in pVICs.
J Transl Med. 2022 Apr 9;20(1):167.
Human neutrophils
10 µM
1-hour pretreatment followed by 4-hour stimulation
To evaluate the effect of Alvelestat on MSU and PMA-induced neutrophil extracellular trap (NET) formation. Results showed that Alvelestat effectively inhibited NET formation.
Int J Mol Sci. 2024 Dec 27;26(1):143.
Human neutrophils
10 µM
1-hour pretreatment followed by 4-hour stimulation
To evaluate the effect of Alvelestat on MSU and PMA-induced neutrophil extracellular trap (NET) formation. Results showed that Alvelestat effectively inhibited NET formation.
Int J Mol Sci. 2024 Dec 27;26(1):143.
Porcine islets
0–25 μM
24 hours
To evaluate the inhibitory effect of alvelestat against the cytotoxicity of neutrophil elastase (NE). Results showed that 5 and 25 μM alvelestat recovered the NE-induced decrease in islet viability.
J Clin Med. 2022 Jul 23;11(15):4290.
Alvelestat/阿尔韦莱司他 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Apoe−/− mice
Western diet-induced aortic valve calcification model
Oral
3 mg/kg
Once a week for 16 weeks
To investigate the effects of Alvelestat on aortic valve calcification. Results showed that Alvelestat alleviated valve thickening, reduced the expression of NE and α-SMA, and improved heart function.
J Transl Med. 2022 Apr 9;20(1):167.
Mice
Hydrochloric acid aspiration-induced acute lung injury model
Subcutaneous injection
5 mg/kg
Immediately after acid aspiration, observed for 12 hours
To evaluate the protective effect of Alvelestat on hydrochloric acid aspiration-induced acute lung injury. Results showed that Alvelestat significantly reduced NET formation in lung tissues, decreased inflammatory cytokine levels, and improved lung histopathology.
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