723331-20-2

Basic information

• Product Name: N-[[[(1S)-1-CARBOXY-3-METHYLBUTYL]AMINO]CARBONYL]-L-GLUTAMIC ACID
• Synonyms: N-[[[(1S)-1-CARBOXY-3-METHYLBUTYL]AMINO]CARBONYL]-L-GLUTAMIC ACID;ZJ 43
• CAS NO: 723331-20-2
• Molecular Formula: C12H20N2O7
• Molecular Weight: 304.3
• Mol File: 723331-20-2.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• Storage Temp.: Store at -20°C
• Solubility: Soluble in DMSO (up to at least mg/ml) or in Water (up to at least 25 mg/ml)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or distilled water may be stored at -20° for up to 2 months.
• CAS DataBase Reference: N-[[[(1S)-1-CARBOXY-3-METHYLBUTYL]AMINO]CARBONYL]-L-GLUTAMIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: N-[[[(1S)-1-CARBOXY-3-METHYLBUTYL]AMINO]CARBONYL]-L-GLUTAMIC ACID(723331-20-2)
• EPA Substance Registry System: N-[[[(1S)-1-CARBOXY-3-METHYLBUTYL]AMINO]CARBONYL]-L-GLUTAMIC ACID(723331-20-2)

Safety Data

• Hazardous Substances Data: 723331-20-2(Hazardous Substances Data)

Usage

Description

N-[[[(1S)-1-CARBOXY-3-METHYLBUTYL]AMINO]CARBONYL]-L-GLUTAMIC ACID, also known as ZJ 43, is a potent inhibitor of glutamate carboxypeptidase II (GCPII) and N-acetylaspartylglutamate (NAAG). It is characterized by its ability to reduce the harmful effects of excessive extracellular glutamate by inhibiting the hydrolysis of NAAG, leading to an increase in synaptic levels of group II mGluRs. N-[[[(1S)-1-CARBOXY-3-METHYLBUTYL]AMINO]CARBONYL]-L-GLUTAMIC ACID has demonstrated efficacy in various pain models, including inflammatory pain and peripheral sensory neurites.

Uses

Used in Pharmaceutical Industry:
N-[[[(1S)-1-CARBOXY-3-METHYLBUTYL]AMINO]CARBONYL]-L-GLUTAMIC ACID is used as a therapeutic agent for the treatment of pain and inflammation. Its application is based on its ability to inhibit glutamate carboxypeptidase II, which in turn increases the activation of mGluR3 by NAAG released from peripheral sensory neurites, resulting in analgesia.
Used in Neurological Applications:
In the field of neurology, N-[[[(1S)-1-CARBOXY-3-METHYLBUTYL]AMINO]CARBONYL]-L-GLUTAMIC ACID is used as a modulator of neurotransmission. By inhibiting the hydrolysis of NAAG, it can potentially influence the synaptic levels of group II mGluRs, which may have implications for the treatment of various neurological disorders associated with glutamate dysregulation.
Used in Research and Development:
N-[[[(1S)-1-CARBOXY-3-METHYLBUTYL]AMINO]CARBONYL]-L-GLUTAMIC ACID is also utilized in research and development for the study of glutamate carboxypeptidase II and its role in neurotransmission, as well as the development of new therapeutic strategies targeting this enzyme for the treatment of pain, inflammation, and other related conditions.

Biological Activity

Potent inhibitor of glutamate carboxypeptidase II and III (GCP II and III/NAAG peptidase/NAALADase) (K i values are 0.8 and 23 nM respectively) that inhibits the hydrolysis of NAAG (IC 50 = 2.4 nM) . Does not directly interact with NMDA or metabotropic glutamate receptors. Reduces neuronal degeneration in a rat model of? traumatic brain injury (TBI) and reduces locomotor activity in the PCP-model of schizophrenia.

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].

IC 50

2.4 nm

References

1) Olszewski?et al.?(2004),?NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR; J. Neurochem.?89?876 2) Yamamoto?et al.?(2004),?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.?20?483 3) Yamamoto?et al.?(2007),?Local administration of N-acetylaspartylglutamate (NAAG) peptidase inhibitors is analgesic in peripheral pain in rats; Eur. J. Neurosci.?25?147 4) Yamamoto?et al.?(2008),?Intracerebroventricular administration of N-acetylaspartylglutamate (NAAG) peptidase inhibitors is analgesic in inflammatory pain; Mol. Pain?4?31 5) Nonaka?et al.?(2017),?A role for the locus coeruleus in the analgesic efficacy of N-acetylaspartylglutamate peptidase (GCPII) inhibitors ZJ43 and 2-PMPA; Mol.Pain?13?1

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