Uses
ZL006 is a potent inhibitor of nNOS/PSD-95 interaction, and inhibits NMDA receptor-mediated NO synthesis.
Biochem/physiol Actions
ZL006 inhibits the ischemia-induced interaction of nNOS with postsynaptic density protein-95 (PSD-95), preventing glutamate-induced excitotoxicity and cerebral ischemic damage. It does not inhibit nNOS itself. ZL006 is brain penetrant, and has been tested in both rat and mouse models of stroke.
in vivo
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].
References
[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. DOI:
10.1038/srep12651[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. DOI:
10.1038/srep12157
