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1400W Dihydrochloride

CAS No. : 214358-33-5

產(chǎn)品活性：1400W dihydrochloride is a potent and selective inhibitor of human inducible NO synthase with K_i values of 7 nM.

研究領(lǐng)域：Immunology/Inflammation

作用靶點(diǎn)：NO Synthase

In Vitro: 1400W is a slow, tight binding inhibitor of human inducible nitric- oxide synthase (iNOS). The slow onset of inhibition by 1400W shows saturation kinetics with a maximal rate constant of 0.028 s^-1 and a binding constant of 2.0 μM. Inhibition is dependent on the cofactor NADPH. 1400W is at least 5000-fold selective for iNOS versus eNOS. In contrast, inhibition of human neuronal NOS and endothelial NOS (eNOS) is relatively weaker, rapidly reversible, and competitive with L-arginine, with K_i values of 2 μM and 50 μM, respectively. 1400W treatment inhibits iNOS expression without affecting nNOS or eNOS. 1400W also reduces NO, 3-NT and MDA production, and prevents neuronal cell apoptosis in cerebral cortex.

In Vivo: 1400W potently (ED₅₀=0.3 mg/kg) reduces the delayed vascular injury in rats attributable to LPS-induced iNOS but fails to exacerbate acute vascular leakage when given concurrently with LPS. Administration of 1400W lowers NOx levels in all the experimental groups. In addition, lipid peroxidation, the percentage of apoptotic cells, and nitrated protein expression fall in the late post-hypoxia period (48 h and 5 days).

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