GW274150 PHOSPHATE

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)

GW274150 phosphate inhibits intracellular iNOS in J774 cells in a time-dependent manner, reaching IC ₅₀ values of 0.2±0.04 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.

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 (ED ₅₀ =3 mg/kg).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.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).