GW274150 (phosphate)

GW274150 phosphate is a potent, selective, orally active and NADPH-dependent inhibitor of human inducible nitric oxide synthase (iNOS) (IC₅₀=2.19 μM; K_d=40 nM) and rat iNOS (ED₅₀=1.15 μM). GW274150 phosphate displays less potency for both humans or rats endothelial NOS (eNOS) and neuronal NOS (nNOS). GW274150 phosphate exerts a protective role in an acute model of lung injury inflammation^[1][2]. IC50 & Target:Kd: 40 nM (iNOS)^[1]
IC50: 2.19 μM (human iNOS); 544 μM (human eNOS); 177 μM (human nNOS)
ED50: 1.15 μM (rat iNOS); 252 μM (rat nNOS)^[1] In Vitro:GW274150 phosphate inhibits intracellular iNOS in J774 cells in a time-dependent manner, reaching IC₅₀ values of 0.2±0.04 μM^[1].
GW274150 is >260-fold and 219-fold selective for iNOS against eNOS and nNOS in rat tissues, respectively. And it displays >100-fold and >80-fold for human iNOS against human eNOS and nNOS, respectively^[1].
In Vivo:GW274150 phosphate is a long-acting (5 h half‐life in rats) iNOS inhibitor and is able to inhibit LPS‐mediated increase in plasma NO2^-, NO3^- levels 14 h after single intraperitoneal dose (ED₅₀=3 mg/kg)^[2].
GW274150 phosphate (intraperitoneal injection; 2.5, 5, and 10 mg/kg; before carrageenan injection) reduces the degree of lung injury induced by carrageenan in a dose-related fashion. Oedema formation and PMNs infiltration in the pleural cavity are also significantly attenuated in a dose‐related manner in rats^[2].
GW274150 phosphate (oral adminstration; 30 mg/kg; twice daily; 7 days) leads to significant neuroprotection, however, it displays a bell-shaped neuroprotective profile, being ineffective at high doses in 6-OHDA rat model of Parkinson disease (PD)^[3].