GW274150 is a potent, selective, orally active and NADPH-dependent inhibitor of human inducible nitric oxide synthase (iNOS) ( IC 50 =2.19 μM; K d =40 nM) and rat iNOS ( ED 50 =1.15 μM). GW274150 also displays less potency for both humans or rats endothelial NOS ( eNOS ) and neuronal NOS ( nNOS ). GW274150 exerts a protective role in an acute model of lung injury inflammation
In Vitro
GW274150 inhibits intracellular iNOS in J774 cells in a time-dependent manner, reaching IC 50 values of 0.2 μM. 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GW274150 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 (ED 50 =3 mg/kg). GW274150 (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. GW274150 (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). MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: SD-ratDosage: 2.5, 5 and 10 mg/kg; single dose Administration: Intraperitoneal injection 5 min before carrageenan injection Result: Exerted a protective role in an acute model of inflammation, carrageenan-induced lung injury.
IC50& Target:Kd: 40 nM (iNOS), IC50: 2.19 μM (human iNOS),544 μM (human eNOS),177 μM (human nNOS) ED50: 1.15 μM (rat iNOS),252 μM (rat nNOS)
