1400W is either an irreversible inhibitor or an extremely slowly reversible inhibitor of human iNOS. Inhibition of human iNOS by 1400W is time-dependent. 1400W is competitive with L-arginine. 1400W is not a substrate for iNOS.
In vivo
1400W selectively prevents microvasculature injury in rats. 1400W is greater than 50-fold more potent against iNOS than eNOS in a rat model of endotoxin-induced vascular injury. Moreover, 1400W also dose-dependently reduces LPS-induced vascular leakage associated with iNOS induction in the colon, lung, liver, kidney, and heart. The maximal protection is close to 100% for all organs except the kidney (kidney:54%). 1400W has an ameliorative effect on both oxidative and nitrosative stress in the kidneys against renal I/R injury in rats. Treatment with 1400W can reduce the rate of growth of solid tumors in mice.
