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ZL006 is a potent inhibitor of nNOS/PSD-95 interaction, and inhibits NMDA receptor-mediated NO synthesis.

ZL006 presents little cytotoxicity, and a growth inhibition of BCECs is not found at low concentration of 0.001, 0.01, 0.1, 1 and 10 μg/mL. The cytotoxicity of T7-P-LPs/ZL006 is significantly enhanced at the concentration of 10 μg/mL. Cellular uptake of ZL006 loads P-LPs and T7-P-LPs after incubation for 0.5 h at the concentrations range from 100 μg/mL to 600 μg/mL in BCECs[1]. ZL006 does not inhibit the nNOS-PDZ/PSD-95-PDZ interaction, or perturb the nNOS β-finger[2].

Compared with P-LPs/ZL006 and free ZL006, T7-P-LPs/ZL006 exhibits a significant increase of drug accumulation in the brain tissue due to its better brain targeting delivery. Compared with free ZL006, P-LPs/ZL006 and T7-P-LPs/ZL006 exhibit a significant decrease of drug accumulation in the liver and kidney[1].

[1]. Wang Z, et al. Enhanced anti-ischemic stroke of ZL006 by T7-conjugated PEGylated liposomes drug delivery system. Sci Rep. 2015 Jul 29;5:12651. [2]. Bach A, et al. Biochemical investigations of the mechanism of action of small molecules ZL006 and IC87201 as potential inhibitors of the nNOS-PDZ/PSD-95-PDZ interactions. Sci Rep. 2015 Jul 16;5:12157.

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