GW-311616 is a long duration, orally bioavailable, and selective human neutrophil elastase (HNE) inhibitor (IC50: 22 nM; Ki: 0.31 nM).

HNE:22 nM , HNE:(ki)0.31 nM

GW-311616 (150 μM;?U937 cells) treatment can increase the protein expression levels of Bax and decrease the expression of Bcl-2.GW-311616 (150 μM; 48 hours) markedly suppresses NE activity in U937 and K562 cells lines. GW-311616 (20-320 μM; 48 hours; U937 cells) treatment inhibits proliferation and induces apoptosis in leukemia cells.

GW-311616 has moderate terminal elimination half-life (t1/2) of 1.1 hours and 1.5 hours for dog (2 mg/kg, oral), rat (2 mg/kg, oral), respectively.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.