生物活性

• 描述Nitric oxide synthase (NOS) catalyzes the formation of nitric oxide and L-citrulline from L-arginine. 1400W 2HCl is a slow, tight binding, selective inhibitor of human inducible nitric-oxide synthase (iNOS). The apparent binding constant of 1400W 2HCl was 2.3 μM at an L-arginine concentration of 0.5 μM. The substrate L-arginine blocked the binding of 1400W 2HCl to iNOS with a K_s value of 3.0 μM. 1400W 2HCl is also a reversible and relatively inefficient inhibitor of human endothelial NOS (eNOS) and neuronal NOS (nNOS). Inhibition of eNOS and nNOS by 1400W 2HCl was competitive with L-arginine with K_i values of 50 μM and 2.0 μM, respectively. Moreover, 1400W 2HCl showed potent inhibitory activity in rat aortic rings with an EC₅₀ value of 0.8 μM. In RAW264.7 cells treated with LPS/IFNγ for 16h, the increased p53 and GAPDH acetylation was blocked by 1400W 2HCl at the concentration of 100 μM. The augmented p300 acetylation, GAPDH–p300 binding and GAPDH-p53 binding in RAW264.7 cells were also abolished by 100 μM 1400W 2HCl. In a rat model of endotoxin-induced microvascular injury, subcutaneous administration of 1400W 2HCl 3h after endotoxin completely suppressed the leakage into ileum with an ED₅₀ value of 0.16 mg/kg.
• 作用机制1400W 2HCl is a tight binding, selective inhibitor of NOS. It is competitive with the substrate L-arginine.