Page last updated: 2024-12-08

isospaglumic acid

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

isospaglumic acid: mediator in the sensitivity of animals to hyperbaric oxygenation; Naaxia is the tradename; apparently can have both a neuroprotective and a neurotoxic effect [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Ac-Asp-Glu : A dipeptide composed of N-acetyl-L-aspartic acid and L-glutamic acid joined by a peptide linkage. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID188803
CHEMBL ID1329032
CHEBI ID73688
SCHEMBL ID288514
MeSH IDM0088582

Synonyms (105)

Synonym
gtpl1405
KBIO1_000662
DIVK1C_000662
SDCCGMLS-0066696.P001
C15544
SPECTRUM_000399
spaglumic acid
tocris-0391
NCGC00016651-01
NCGC00024569-01
BSPBIO_003230
PRESTWICK2_001091
IDI1_000662
SPECTRUM5_001840
BSPBIO_002378
isospaglumic acid
3106-85-2
n-acetylaspartylglutamate
naag
NCGC00024569-02
acide isospaglumique [french]
naaga
isospaglumic acid [inn]
acido isospaglumico [spanish]
acidum isospaglumicum [latin]
n-(n-acetyl-l-alpha-aspartyl)-l-glutamic acid
n-acetyl-1-aspartylglutamic acid
KBIO2_003447
KBIO2_006015
KBIO3_001598
KBIOGR_001565
KBIOSS_000879
KBIO2_000879
SPBIO_001502
SPECTRUM4_000873
SPECTRUM3_000759
SPECTRUM2_001571
NINDS_000662
SPBIO_003051
PRESTWICK0_001091
PRESTWICK1_001091
SPECTRUM1503630
n-ac-d-e
n-acetyl-asp-glu
HMS502B04
HMS1571K04
n-acetyl-a-aspartylglutamic acid
(2s)-2-[[(2s)-2-acetamido-4-hydroxy-4-oxobutanoyl]amino]pentanedioic acid
n-acetylaspartylglutamic acid
unii-1w8m12wxyl
acido isospaglumico
acidum isospaglumicum
acide isospaglumique
1w8m12wxyl ,
nsc758468
pharmakon1600-01503630
n-acetyl-l-aspartyl-l-glutamic acid
ac-asp-glu
n-acetyl-l-alpha-aspartyl-l-glutamic acid
n-acetyl-l-asp-l-glu
CCG-38888
NCGC00016651-02
chebi:73688 ,
CHEMBL1329032
isospaglumic acid [mart.]
isospaglumic acid [who-dd]
n-(n-acetyl-l-.alpha.-aspartyl)-l-glutamic acid
SCHEMBL288514
(2s)-2-[(3s)-3-acetamido-3-formamidopropanoic acid]pentanedioic acid
n-acetylaspartylglutamate (naag)
bdbm17658
[3h]naag
AKOS024457865
W-202283
?-naag
OPVPGKGADVGKTG-BQBZGAKWSA-N
AB00053333_02
DTXSID3091535
mfcd00076652
SR-01000597665-1
SR-01000597665-2
sr-01000597665
SBI-0052840.P002
ac-asp-glu-oh
acetyl-a-l-aspartylglutamic acid
alpha-spaglumic acid
n-acetyl-alpha-l-aspartyl-l-glutamic acid
a-spaglumic acid
acetyl-alpha-l-aspartylglutamic acid
n-acetyl-alpha-aspartylglutamic acid
n-acetyl-a-l-aspartyl-l-glutamic acid
n-(n-acetylaspartyl)glutamic acid
CS-0020591
HY-100921
2-[(2-acetamido-3-carboxy-1-oxopropyl)amino]pentanedioic acid
(s)-2-((s)-2-acetamido-3-carboxypropanamido)pentanedioic acid
HMS3675I03
Q2394106
HMS3411I03
(2s)-2-[[(2s)-2-acetamido-3-carboxypropanoyl]amino]pentanedioic acid
l-glutamic acid, n-acetyl-l-alpha-aspartyl-
spaglumic-acid
n-acetylaspartylglutamic acidnaag
AS-76948
l-glutamic acid, n-acetyl-l-a-aspartyl-

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" Prior incubation with NMDA (MK-801) or non-NMDA (glutamate diethyl ester, (GDEE] receptor antagonists protected the slices against NAAG-mediated neurotoxicity, indicating the possible involvement of both of these classes of receptors in the toxic action of NAAG."( Toxicity of N-acetylaspartylglutamate and its protection by NMDA and non-NMDA receptor antagonists.
Pai, KS; Ravindranath, V, 1991
)
0.28

Compound-Compound Interactions

ExcerptReferenceRelevance
" In this study we examined whether administration of N-acetyl-aspartyl-glutamate (NAAG) in combination with mild hypothermia could improve striatal neuroprotection in the endothelin-1 rat model."( Neuroprotective effect of N-acetyl-aspartyl-glutamate in combination with mild hypothermia in the endothelin-1 rat model of focal cerebral ischaemia.
Ebinger, G; Hachimi-Idrissi, S; Michotte, Y; Sarre, S; Van Hemelrijck, A, 2005
)
0.33

Bioavailability

ExcerptReferenceRelevance
" However, the poor oral bioavailability of NAAG and 2-PMPA limits their practical use in humans."( Oral administration of the NAALADase inhibitor GPI-5693 attenuates cocaine-induced reinstatement of drug-seeking behavior in rats.
Ashby, CR; Gardner, EL; Li, J; Peng, XQ; Slusher, BS; Thomas, A; Wozniak, K; Xi, ZX, 2010
)
0.36
" Therefore, this study highlights a potential role for nuclear ASPA expression in GSC malignancy and suggests that the use of NAA or NAAG is not an appropriate therapeutic approach to increase acetate bioavailability in glioma."( N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) promote growth and inhibit differentiation of glioma stem-like cells.
Jaworski, DM; Lawler, SE; Long, PM; Moffett, JR; Namboodiri, AMA; Viapiano, MS, 2013
)
0.39

Dosage Studied

ExcerptRelevanceReference
" Both treatments were used at a dosage of 1 drop 4 times per day."( [N-acetyl-aspartylglutamic acid eye drops in allergic-type conjuctivitis. Double-blind comparative clinical study].
Bonnet, M; Ducournau, D; Lumbroso, P; Serpin, G, 1985
)
0.27
" At similar dosage conditions (one puff per nostril, four times daily, for 3 weeks), no significant differences between the treatments were discernible in the primary efficacy parameters (scores, patients' and physicians' opinion)."( Clinical efficacy of N-acetyl-aspartyl-glutamic acid nasal spray in children suffering from pollinosis: a double-blind multicentre study.
Bertrand, B; Dab, R; Daele, J; van Cauwenberge, P; van den Broeck, R, 1995
)
0.29
" The glutamate- or NAAG-mediated blockage of calcium channels showed indistinguishable dose-response curves, with K1/2 = 388 and 350 nM for glutamate and NAAG, respectively."( Glutamate and N-acetylaspartylglutamate block HVA calcium currents in frog olfactory bulb interneurons via an mGluR2/3-like receptor.
Bischofberger, J; Schild, D, 1996
)
0.29
"Ten patients with allergic seasonal rhinitis were included in this randomized double-blind crossover trial of a 6% wt/vol solution of NAAGA (daily dosage 84 mg) versus placebo (lactose)."( N-acetyl-aspartyl-glutamic acid inhibits cellular recruitment and mediator release during the late allergen-induced nasal reaction.
Cottini, M; Lorini, M; Miadonna, A; Milazzo, N; Salmaso, C; Tedeschi, A, 1998
)
0.3
" Inhibition of the neuropeptidase glutamate carboxypeptidase II (GCPII) has previously been shown to ameliorate cognitive impairment in EAE, but dosing has not yet been optimized and only a prevention treatment paradigm has been explored."( Dose-dependent inhibition of GCPII to prevent and treat cognitive impairment in the EAE model of multiple sclerosis.
Alt, J; Hollinger, KR; Kaplin, AI; Riehm, AM; Slusher, BS, 2016
)
0.43
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
human metaboliteAny mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
dipeptideAny molecule that contains two amino-acid residues connected by peptide linkages.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (10)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASEHomo sapiens (human)Potency3.54810.003245.467312,589.2998AID2517
Chain A, TYROSYL-DNA PHOSPHODIESTERASEHomo sapiens (human)Potency20.48390.004023.8416100.0000AID485290; AID489007
Chain A, ATP-DEPENDENT DNA HELICASE Q1Homo sapiens (human)Potency7.94330.125919.1169125.8920AID2549
phosphopantetheinyl transferaseBacillus subtilisPotency56.23410.141337.9142100.0000AID1490
aldehyde dehydrogenase 1 family, member A1Homo sapiens (human)Potency37.65050.011212.4002100.0000AID1030
potassium voltage-gated channel subfamily H member 2 isoform dHomo sapiens (human)Potency14.12540.01789.637444.6684AID588834
DNA polymerase kappa isoform 1Homo sapiens (human)Potency12.58930.031622.3146100.0000AID588579
lamin isoform A-delta10Homo sapiens (human)Potency0.50120.891312.067628.1838AID1487
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Glutamate carboxypeptidase 2Homo sapiens (human)Km11.02501.20001.20001.2000AID291424; AID636705; AID636708; AID636710
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (3)

Processvia Protein(s)Taxonomy
proteolysisGlutamate carboxypeptidase 2Homo sapiens (human)
folic acid-containing compound metabolic processGlutamate carboxypeptidase 2Homo sapiens (human)
C-terminal protein deglutamylationGlutamate carboxypeptidase 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (7)

Processvia Protein(s)Taxonomy
metallocarboxypeptidase activityGlutamate carboxypeptidase 2Homo sapiens (human)
peptidase activityGlutamate carboxypeptidase 2Homo sapiens (human)
dipeptidase activityGlutamate carboxypeptidase 2Homo sapiens (human)
metal ion bindingGlutamate carboxypeptidase 2Homo sapiens (human)
Ac-Asp-Glu bindingGlutamate carboxypeptidase 2Homo sapiens (human)
tetrahydrofolyl-poly(glutamate) polymer bindingGlutamate carboxypeptidase 2Homo sapiens (human)
carboxypeptidase activityGlutamate carboxypeptidase 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (5)

Processvia Protein(s)Taxonomy
cytoplasmGlutamate carboxypeptidase 2Homo sapiens (human)
plasma membraneGlutamate carboxypeptidase 2Homo sapiens (human)
cell surfaceGlutamate carboxypeptidase 2Homo sapiens (human)
membraneGlutamate carboxypeptidase 2Homo sapiens (human)
extracellular exosomeGlutamate carboxypeptidase 2Homo sapiens (human)
plasma membraneGlutamate carboxypeptidase 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (17)

Assay IDTitleYearJournalArticle
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID540299A screen for compounds that inhibit the MenB enzyme of Mycobacterium tuberculosis2010Bioorganic & medicinal chemistry letters, Nov-01, Volume: 20, Issue:21
Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: novel antibacterial agents against Mycobacterium tuberculosis.
AID588519A screen for compounds that inhibit viral RNA polymerase binding and polymerization activities2011Antiviral research, Sep, Volume: 91, Issue:3
High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors.
AID1159550Human Phosphogluconate dehydrogenase (6PGD) Inhibitor Screening2015Nature cell biology, Nov, Volume: 17, Issue:11
6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling.
AID636708Activity of recombinant human glutamate carboxypeptidase 2 K699S mutant expressed in Drosophila Schneider's S2 cells using [3H]NAAG as substrate after 30 mins2011Journal of medicinal chemistry, Nov-10, Volume: 54, Issue:21
Novel substrate-based inhibitors of human glutamate carboxypeptidase II with enhanced lipophilicity.
AID636714Ratio of Km recombinant human glutamate carboxypeptidase 2 K699S mutant to Km for wild type recombinant human glutamate carboxypeptidase 22011Journal of medicinal chemistry, Nov-10, Volume: 54, Issue:21
Novel substrate-based inhibitors of human glutamate carboxypeptidase II with enhanced lipophilicity.
AID636710Activity of recombinant human glutamate carboxypeptidase 2 expressed in Drosophila Schneider's S2 cells using [3H]NAAG as substrate after 30 mins2011Journal of medicinal chemistry, Nov-10, Volume: 54, Issue:21
Novel substrate-based inhibitors of human glutamate carboxypeptidase II with enhanced lipophilicity.
AID636709Ratio of Kcat to Km recombinant human glutamate carboxypeptidase 2 K699S mutant expressed in Drosophila Schneider's S2 cells using [3H]NAAG as substrate after 30 mins2011Journal of medicinal chemistry, Nov-10, Volume: 54, Issue:21
Novel substrate-based inhibitors of human glutamate carboxypeptidase II with enhanced lipophilicity.
AID636705Activity of recombinant human glutamate carboxypeptidase 22011Journal of medicinal chemistry, Nov-10, Volume: 54, Issue:21
Novel substrate-based inhibitors of human glutamate carboxypeptidase II with enhanced lipophilicity.
AID636711Ratio of Kcat to Km recombinant human glutamate carboxypeptidase 2 expressed in Drosophila Schneider's S2 cells using [3H]NAAG as substrate after 30 mins2011Journal of medicinal chemistry, Nov-10, Volume: 54, Issue:21
Novel substrate-based inhibitors of human glutamate carboxypeptidase II with enhanced lipophilicity.
AID291424Inhibition of human recombinant glutamate carboxypeptidase 2 by radioenzymatic assay2007Journal of medicinal chemistry, Jul-12, Volume: 50, Issue:14
Structural insight into the pharmacophore pocket of human glutamate carboxypeptidase II.
AID678882TP_TRANSPORTER: inhibition of Gly-Sar uptake (Gly-Sar: 10 uM) in PEPT2-expressing SK-N-SH cells1998The American journal of physiology, 10, Volume: 275, Issue:4
Electrophysiological characteristics of the proton-coupled peptide transporter PEPT2 cloned from rat brain.
AID636707Ratio of Kcat to Km for recombinant human glutamate carboxypeptidase 22011Journal of medicinal chemistry, Nov-10, Volume: 54, Issue:21
Novel substrate-based inhibitors of human glutamate carboxypeptidase II with enhanced lipophilicity.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (459)

TimeframeStudies, This Drug (%)All Drugs %
pre-199067 (14.60)18.7374
1990's117 (25.49)18.2507
2000's143 (31.15)29.6817
2010's112 (24.40)24.3611
2020's20 (4.36)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 8.43

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index8.43 (24.57)
Research Supply Index6.22 (2.92)
Research Growth Index4.65 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (8.43)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials31 (6.61%)5.53%
Reviews33 (7.04%)6.00%
Case Studies6 (1.28%)4.05%
Observational1 (0.21%)0.25%
Other398 (84.86%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Study of the Clinical and Biological Efficacity of NAAXIA SINEĀ® in Vernal Keratoconjunctivitis [NCT00357019]Phase 40 participants Interventional2001-04-30Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]