GW311616A

BeschreibungGW 311616A is an inhibitor of neutrophil elastase (IC50 = 100 nM). It is selective for neutrophil elastase (IC50 = 22 nM for the human enzyme) over trypsin, cathepsin G, and plasmin (IC50s = >100 μM for all), as well as chymotrypsin and tissue plasminogen activator (IC50s = >3 μM for both), in cell-free assays. GW 311616A (20 μM) inhibits the formation of neutrophil extracellular traps (NETs) induced by phorbol 12-myristate 13-acetate (PMA; ) in isolated human neutrophils. It inhibits intraneutrophil elastase activity in isolated dog blood six hours after administration of a 0.22 mg/kg dose. GW 311616A also inhibits neutrophil elastase in the liver in a mouse model of liver ischemia-reperfusion injury when administered at a dose of 2 mg/kg.