GW311616

GW-311616 is a potent, orally bioavailable, long duration and selective human neutrophil elastase (HNE) inhibitor with IC₅₀ value of 22 nM and K_i value of 0.31 nM^[1]. IC50 & Target: IC50: 22 nM (HNE)^[1] Ki: 0.31 nM (HNE)^[1] In Vitro: GW-311616 (150 μM; 48 hours) markedly suppresses NE activity in U937 and K562 cells lines^[2].
GW-311616 (20-320 μM; 48 hours; U937 cells) treatment inhibits proliferation and induces apoptosis in leukemia cells^[2].
GW-311616 (150 μM; U937 cells) treatment can increase the protein expression levels of Bax and decrease the expression of Bcl-2^[2]. In Vivo: GW-311616 (2 mg/kg; oral administration) rapidly abolishes the circulation of neutrophil elastase (NE) in dogs, while >90% inhibition is maintained for 4 days. This prolonged effect is independent to be due to penetration of neutrophils in bone marrow by orally administrated GW-311616. GW-311616 has moderate terminal elimination half-life (t_1/2) of 1.1 hours and 1.5 hours for dog (2 mg/kg, oral), rat (2 mg/kg, oral), respectively^[3].