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].
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