IC50: 2.4 nM
ZJ-43 is a N-acetylaspartylglutamate (NAAG) peptidase inhibitor.
The peptide neurotransmitter N-acetylaspartylglutamate (NAAG) is reported to act as an agonist at group II metabotropic glutamate receptors. NAAG is inactivated by extracellular peptidase activity leading to yielding glutamate and N-acetylaspartate.
In vitro: As a potent inhibitor of glutamate carboxypeptidase II and III (GCP II and III) with Kivalues of 0.8 and 23 nM respectively, ZJ-43 inhibited the hydrolysis of NAAG via indirect interactions with NMDA or metabotropic glutamate receptors [1].
In vivo: Intravenous injection of ZJ-43 coiuld suppress both phases of the agitation behaviour induced by paw formalin injection in the rat neuropathic pain model. Moreover, intravenous administration of ZJ-43 attenuated the level of mechanical allodynia induced by the nerve ligation. These effects of ZJ-43 in both the formalin test and the partial sciatic nerve ligation model were completely antagonized by pretreatment with LY-341495, which was a highly selective group II mGluR antagonist [1].
Clinical trial: N/A
Reference:
[1] Yamamoto T1,Hirasawa S,Wroblewska B,Grajkowska E,Zhou J,Kozikowski A,Wroblewski J,Neale JH. Antinociceptive effects of N-acetylaspartylglutamate (NAAG) peptidase inhibitors ZJ-11, ZJ-17 and ZJ-43 in the rat formalin test and in the rat neuropathic pain model. Eur J Neurosci.2004 Jul;20(2):483-94.