GW311616A

Description

GW 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.

References

[1] macdonald sj1, dowle md, harrison la, shah p, johnson mr, inglis gg, clarke gd, smith ra, humphreys d, molloy cr, amour a, dixon m, murkitt g, godward re, padfield t, skarzynski t, singh om, kumar ka, fleetwood g, hodgson st, hardy gw, finch h. the discovery of a potent, intracellular, orally bioavailable,long duration inhibitor of human neutrophil elastase-gw311616a a development candidate. bioorg med chem lett. 2001 apr 9;11(7):895-8.