Compounds > gpi 5693
Page last updated: 2024-11-12

gpi 5693

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Description

2-(3-mercaptopropyl)pentanedioic acid: inhibits glutamate carboxypeptidase II; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID10198171
CHEMBL ID303352
SCHEMBL ID787800
MeSH IDM0493895

Synonyms (22)

Synonym
2-mppa
bdbm17755
2-(3-sulfanylpropyl)pentanedioic acid
chembl303352 ,
2-(3-mercaptopropyl)pentanedioic acid
gpi 5693
unii-tv8f3s5klg
tv8f3s5klg ,
pentanedioic acid, 2-(3-mercaptopropyl)-
254737-29-6
FNLNSQHJKVQCBP-UHFFFAOYSA-N
SCHEMBL787800
AKOS024458465
2-[3-mercaptopropyl]pentanedioic acid
EX-A7083
BCP29740
2-(3-mercaptopropyl)pentanedioic acid;2-(3-sulfanylpropyl)pentanedioic acid
MS-23124
HY-103345
gpi-5693
naal-1
gpi5693

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" Blood samples were collected for pharmacokinetic and biochemical/haematological safety analysis, vital signs, ECG and adverse event checks were performed regularly up to 48 h postdose."( The central nervous system effects, pharmacokinetics and safety of the NAALADase-inhibitor GPI 5693.
Bortey, E; Burak, ES; Cohen, AF; de Kam, ML; de Visser, SJ; Hilt, DC; Limsakun, T; Slusher, BS; van der Post, JP; van Gerven, JM; Vornov, J; Woelfler, M, 2005)		0.55
" Gastro-intestinal (GI) adverse effects were frequent at higher doses."( The central nervous system effects, pharmacokinetics and safety of the NAALADase-inhibitor GPI 5693.
Bortey, E; Burak, ES; Cohen, AF; de Kam, ML; de Visser, SJ; Hilt, DC; Limsakun, T; Slusher, BS; van der Post, JP; van Gerven, JM; Vornov, J; Woelfler, M, 2005)		0.55
"NAALADase inhibition with GPI 5693 was safe and tolerable in healthy subjects."( The central nervous system effects, pharmacokinetics and safety of the NAALADase-inhibitor GPI 5693.
Bortey, E; Burak, ES; Cohen, AF; de Kam, ML; de Visser, SJ; Hilt, DC; Limsakun, T; Slusher, BS; van der Post, JP; van Gerven, JM; Vornov, J; Woelfler, M, 2005)		0.85

Pharmacokinetics

ExcerptReferenceRelevance
" Blood samples were collected for pharmacokinetic and biochemical/haematological safety analysis, vital signs, ECG and adverse event checks were performed regularly up to 48 h postdose."( The central nervous system effects, pharmacokinetics and safety of the NAALADase-inhibitor GPI 5693.
Bortey, E; Burak, ES; Cohen, AF; de Kam, ML; de Visser, SJ; Hilt, DC; Limsakun, T; Slusher, BS; van der Post, JP; van Gerven, JM; Vornov, J; Woelfler, M, 2005)		0.55
" The pharmacokinetic variability was largest after the 300 mg and 750 mg dose, resulting in a SD of approximately 50% of the C(max)."( The central nervous system effects, pharmacokinetics and safety of the NAALADase-inhibitor GPI 5693.
Bortey, E; Burak, ES; Cohen, AF; de Kam, ML; de Visser, SJ; Hilt, DC; Limsakun, T; Slusher, BS; van der Post, JP; van Gerven, JM; Vornov, J; Woelfler, M, 2005)		0.55

Bioavailability

ExcerptReferenceRelevance
" The most potent thiol-based inhibitor, 2-(3-mercaptopropyl)pentanedioic acid (IC(50) = 90 nM), was found to be orally bioavailable in rats and exhibited efficacy in an animal model of neuropathic pain following oral administration."( Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
Burak, E; Delahanty, G; Grella, BS; Jackson, PF; Ko, YS; Li, W; Limsakun, T; Liu, Q; Maclin, KM; Majer, P; Poláková, J; Rojas, C; Shaffer, KA; Slusher, BS; Stoermer, D; Tsukamoto, T; Vitharana, D; Wang, EY; Wozniak, KM; Zakrzewski, A, 2003)		0.32
" 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
" In addition, E2072 was found to be orally available with an absolute bioavailability of ∼30% in rats and ∼39% in monkeys."( Reversible disulfide formation of the glutamate carboxypeptidase II inhibitor E2072 results in prolonged systemic exposures in vivo.
Alt, J; Hoover, R; Rais, R; Rojas, C; Rudek, MA; Slusher, BS; Tsukamoto, T; Wozniak, K, 2012)		0.38
" The potent, orally bioavailable GCP II inhibitor 2-(3-mercaptopropyl) pentanedioic acid (2-MPPA) is effective in preclinical models of diseases where excess glutamate release is implicated, including neuropathic pain, and was the first GCP II inhibitor to be administered to man."( Pharmacokinetics and pharmacodynamics of the glutamate carboxypeptidase II inhibitor 2-MPPA show prolonged alleviation of neuropathic pain through an indirect mechanism.
Rais, R; Rojas, C; Slusher, BS; Vornov, JJ; Wozniak, KM; Wu, Y, 2013)		0.39
" An orally bioavailable GCP II inhibitor, 2-(3-mercaptopropyl) pentanedioic acid (2-MPPA), was administered daily at a dose of 30 mg/kg starting from the onset of pyridoxine injections."( Glutamate carboxypeptidase II inhibition behaviorally and physiologically improves pyridoxine-induced neuropathy in rats.
Callizot, N; Potter, MC; Slusher, BS; Wozniak, KM, 2014)		0.4
" Unfortunately no GCP-II inhibitor has advanced clinically, largely due to their highly polar nature resulting in insufficient oral bioavailability and limited brain penetration."( Selective CNS Uptake of the GCP-II Inhibitor 2-PMPA following Intranasal Administration.
Alt, J; Giroux, M; Niwa, M; Rais, R; Rojas, C; Sawa, A; Slusher, BS; Stathis, M; Wozniak, K; Wu, Y, 2015)		0.42

Dosage Studied

ExcerptRelevanceReference
" The relationships between dosing regimen, pharmacokinetics, and analgesia in a neuropathic pain model were examined in rats to aid development of clinical dosing."( Pharmacokinetics and pharmacodynamics of the glutamate carboxypeptidase II inhibitor 2-MPPA show prolonged alleviation of neuropathic pain through an indirect mechanism.
Rais, R; Rojas, C; Slusher, BS; Vornov, JJ; Wozniak, KM; Wu, Y, 2013)		0.39
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Cytochrome P450 1A2Homo sapiens (human)IC50 (µMol)0.09000.00011.774010.0000AID540096
Glutamate carboxypeptidase 2Homo sapiens (human)IC50 (µMol)0.09000.00030.83169.5000AID1067872; AID1210717; AID1797656; AID1797657; AID540096; AID690661; AID74530; AID74531
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Glutamate carboxypeptidase 2Homo sapiens (human)EC50 (µMol)0.01300.00060.00680.0130AID74529
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (27)

Processvia Protein(s)Taxonomy
steroid catabolic processCytochrome P450 1A2Homo sapiens (human)
porphyrin-containing compound metabolic processCytochrome P450 1A2Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 1A2Homo sapiens (human)
cholesterol metabolic processCytochrome P450 1A2Homo sapiens (human)
estrogen metabolic processCytochrome P450 1A2Homo sapiens (human)
toxin biosynthetic processCytochrome P450 1A2Homo sapiens (human)
post-embryonic developmentCytochrome P450 1A2Homo sapiens (human)
alkaloid metabolic processCytochrome P450 1A2Homo sapiens (human)
regulation of gene expressionCytochrome P450 1A2Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 1A2Homo sapiens (human)
dibenzo-p-dioxin metabolic processCytochrome P450 1A2Homo sapiens (human)
epoxygenase P450 pathwayCytochrome P450 1A2Homo sapiens (human)
lung developmentCytochrome P450 1A2Homo sapiens (human)
methylationCytochrome P450 1A2Homo sapiens (human)
monocarboxylic acid metabolic processCytochrome P450 1A2Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 1A2Homo sapiens (human)
retinol metabolic processCytochrome P450 1A2Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 1A2Homo sapiens (human)
cellular respirationCytochrome P450 1A2Homo sapiens (human)
aflatoxin metabolic processCytochrome P450 1A2Homo sapiens (human)
hydrogen peroxide biosynthetic processCytochrome P450 1A2Homo sapiens (human)
oxidative demethylationCytochrome P450 1A2Homo sapiens (human)
cellular response to cadmium ionCytochrome P450 1A2Homo sapiens (human)
omega-hydroxylase P450 pathwayCytochrome P450 1A2Homo sapiens (human)
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 (21)

Processvia Protein(s)Taxonomy
monooxygenase activityCytochrome P450 1A2Homo sapiens (human)
iron ion bindingCytochrome P450 1A2Homo sapiens (human)
protein bindingCytochrome P450 1A2Homo sapiens (human)
electron transfer activityCytochrome P450 1A2Homo sapiens (human)
oxidoreductase activityCytochrome P450 1A2Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygenCytochrome P450 1A2Homo sapiens (human)
enzyme bindingCytochrome P450 1A2Homo sapiens (human)
heme bindingCytochrome P450 1A2Homo sapiens (human)
demethylase activityCytochrome P450 1A2Homo sapiens (human)
caffeine oxidase activityCytochrome P450 1A2Homo sapiens (human)
aromatase activityCytochrome P450 1A2Homo sapiens (human)
estrogen 16-alpha-hydroxylase activityCytochrome P450 1A2Homo sapiens (human)
estrogen 2-hydroxylase activityCytochrome P450 1A2Homo sapiens (human)
hydroperoxy icosatetraenoate dehydratase activityCytochrome P450 1A2Homo sapiens (human)
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 (7)

Processvia Protein(s)Taxonomy
endoplasmic reticulum membraneCytochrome P450 1A2Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 1A2Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 1A2Homo sapiens (human)
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 (46)

Assay IDTitleYearJournalArticle
AID234098Selectivity for zinc metalloprotease over matrix metalloprotease 2(MMP-2) for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234099Selectivity for zinc metalloprotease over matrix metalloprotease 2(MMP-2) for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID26209Pharmacokinetic constant Area under curve(AUC) was determined after orally administered dose of 10 mgkg in rats2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234101Selectivity for zinc metalloprotease over matrix metalloprotease 3(MMP-3) for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234094Selectivity for zinc metalloprotease over angiotensin converting enzyme(ACE) for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234062Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate AMPA(phencyclidine) receptor for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID29059Half life after orally administered dose of 10 mgkg in rats2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234264Selectivity for zinc metalloprotease over neutral endopeptidase (NEP) for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID690661Inhibition of human recombinant GCP2 using N-acetyl-L-aspartyl-[3H]-L-glutamate as substrate by microplate assay2012Journal of medicinal chemistry, Jun-28, Volume: 55, Issue:12
Design, synthesis, and pharmacological evaluation of glutamate carboxypeptidase II (GCPII) inhibitors based on thioalkylbenzoic acid scaffolds.
AID1210717Inhibition of GCP-2 (unknown origin)2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Reversible disulfide formation of the glutamate carboxypeptidase II inhibitor E2072 results in prolonged systemic exposures in vivo.
AID29450Bioavailability after orally administered dose of 10 mgkg in rats2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234071Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate kainate receptor for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID74531Inhibition of Glutamate carboxypeptidase II2003Bioorganic & medicinal chemistry letters, Jul-07, Volume: 13, Issue:13
Synthesis and biological evaluation of hydroxamate-Based inhibitors of glutamate carboxypeptidase II.
AID234097Selectivity for zinc metalloprotease over matrix metalloprotease 1(MMP-1) for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234095Selectivity for zinc metalloprotease over angiotensin converting enzyme(ACE) for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234263Selectivity for zinc metalloprotease over matrix metalloprotease 9(MMP-9) for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID74530Inhibition of N-acetyl-L-aspartyl-[3H]L-glutamate binding to glutamate carboxypeptidase II (GCP II)2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234102Selectivity for zinc metalloprotease over matrix metalloprotease 7(MMP-7) for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234068Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate NMDA(glycine) receptor for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID540096Inhibition of GCP2 by top scintillation counter in presence of 30 nM NAA[3]G2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
The discovery and structure-activity relationships of indole-based inhibitors of glutamate carboxypeptidase II.
AID234103Selectivity for zinc metalloprotease over matrix metalloprotease 7(MMP-7) for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234061Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate AMPA receptor for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234100Selectivity for zinc metalloprotease over matrix metalloprotease 3(MMP-3) for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID1067869Prodrug conversion in rat liver microsomes assessed as 2-MPPA formation at 10 uM by LC/MS/MS analysis2014Journal of medicinal chemistry, Jan-09, Volume: 57, Issue:1
δ-Thiolactones as prodrugs of thiol-based glutamate carboxypeptidase II (GCPII) inhibitors.
AID234066Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate NMDA(agonist) receptor for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID74529Concentration required for the neuroprotective effect determined by inhibition of GCP II2003Bioorganic & medicinal chemistry letters, Jul-07, Volume: 13, Issue:13
Synthesis and biological evaluation of hydroxamate-Based inhibitors of glutamate carboxypeptidase II.
AID234063Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate AMPA(phencyclidine) receptor for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234065Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate AMPA(polyamine) receptor for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234060Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate AMPA receptor for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID242379In vitro inhibition of N-acetyl-L-aspartyl-[3H]L-glutamate binding to Glutamate carboxypeptidase II2005Journal of medicinal chemistry, Apr-07, Volume: 48, Issue:7
Enantiospecificity of glutamate carboxypeptidase II inhibition.
AID1067872Inhibition of GCP2 (unknown origin)2014Journal of medicinal chemistry, Jan-09, Volume: 57, Issue:1
δ-Thiolactones as prodrugs of thiol-based glutamate carboxypeptidase II (GCPII) inhibitors.
AID234069Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate NMDA(glycine) receptor for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234262Selectivity for zinc metalloprotease over matrix metalloprotease 9(MMP-9) for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234067Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate NMDA(agonist) receptor for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234070Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate kainate receptor for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID28499Plasma concentration was determined after orally administered dose of 10 mgkg in rats2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID690671AUC (0 to infinity) in fasted rat at 10 mg/kg, po2012Journal of medicinal chemistry, Jun-28, Volume: 55, Issue:12
Design, synthesis, and pharmacological evaluation of glutamate carboxypeptidase II (GCPII) inhibitors based on thioalkylbenzoic acid scaffolds.
AID234064Selectivity for glutamate carboxypeptidase II (GCP II) over glutamate AMPA(polyamine) receptor for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID26208Pharmacokinetic constant Area under curve(AUC) was determined after intravenously administered dose of 10 mgkg in rats2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID29058Half life after intravenously administered dose of 10 mgkg in rats2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID246302Neuroprotective effect against ischemic injury with median effective concentration in in rat2005Journal of medicinal chemistry, Apr-07, Volume: 48, Issue:7
Enantiospecificity of glutamate carboxypeptidase II inhibition.
AID234265Selectivity for zinc metalloprotease over neutral endopeptidase (NEP) for >=50% stimulation2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID234096Selectivity for zinc metalloprotease over matrix metalloprotease 1(MMP-1) for >=50% inhibition2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID29546Pharmacokinetic constant(Tmax) after orally administered dose of 10 mgkg in rats2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Synthesis and biological evaluation of thiol-based inhibitors of glutamate carboxypeptidase II: discovery of an orally active GCP II inhibitor.
AID1797657Microplate GCPII Radioactivity-Based Assay from Article 10.1021/jm051019l: \\Structural optimization of thiol-based inhibitors of glutamate carboxypeptidase II by modification of the P1' side chain.\\2006Journal of medicinal chemistry, May-18, Volume: 49, Issue:10
Structural optimization of thiol-based inhibitors of glutamate carboxypeptidase II by modification of the P1' side chain.
AID1797656Microplate GCPII Radioactivity-Based Assay from Article 10.1021/jm049258g: \\Enantiospecificity of glutamate carboxypeptidase II inhibition.\\2005Journal of medicinal chemistry, Apr-07, Volume: 48, Issue:7
Enantiospecificity of glutamate carboxypeptidase II inhibition.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (18)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's8 (44.44)29.6817
2010's9 (50.00)24.3611
2020's1 (5.56)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 11.48

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 Index11.48 (24.57)
Research Supply Index3.00 (2.92)
Research Growth Index4.48 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (11.48)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (5.56%)5.53%
Reviews1 (5.56%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other16 (88.89%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
pyridoxine
4,5-bis(hydroxymethyl)-2-methylpyridin-3-ol: structure in first source. vitamin B6 : Any member of the group of pyridines that exhibit biological activity against vitamin B6 deficiency. Vitamin B6 deficiency is associated with microcytic anemia, electroencephalographic abnormalities, dermatitis with cheilosis (scaling on the lips and cracks at the corners of the mouth) and glossitis (swollen tongue), depression and confusion, and weakened immune function. Vitamin B6 consists of the vitamers pyridoxine, pyridoxal, and pyridoxamine and their respective 5'-phosphate esters (and includes their corresponding ionized and salt forms).		2.110hydroxymethylpyridine;
methylpyridines;
monohydroxypyridine;
vitamin B6		cofactor;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
sucrose
Saccharum: A plant genus of the family POACEAE widely cultivated in the tropics for the sweet cane that is processed into sugar.		2.0510glycosyl glycosidealgal metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
osmolyte;
Saccharomyces cerevisiae metabolite;
sweetening agent
xanthenes
Xanthenes: Compounds with three aromatic rings in linear arrangement with an OXYGEN in the center ring.		2.7330xanthene
isospaglumic acid
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. Ac-Asp-Glu : A dipeptide composed of N-acetyl-L-aspartic acid and L-glutamic acid joined by a peptide linkage.		2.4620dipeptidehuman metabolite
sq 14,603
2-benzyl-3-mercaptopropanoic acid: structure; carboxypeptidase inhibitor		2.0110
eglumetad
eglumetad: LY-354740 is the active isomer, LY-366563 is the inactive isomer, and LY 314582 is the racemate; structure given in first source		2.0610L-alpha-amino acid
cocaine
Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.. cocaine : A tropane alkaloid obtained from leaves of the South American shrub Erythroxylon coca.		2.0510benzoate ester;
methyl ester;
tertiary amino compound;
tropane alkaloid		adrenergic uptake inhibitor;
central nervous system stimulant;
dopamine uptake inhibitor;
environmental contaminant;
local anaesthetic;
mouse metabolite;
plant metabolite;
serotonin uptake inhibitor;
sodium channel blocker;
sympathomimetic agent;
vasoconstrictor agent;
xenobiotic
gamma-glutamyl hydroxamate
glutamine hydroxamate : A hydroxamic acid that is L-glutamine hydroxylated at N-5.		2.0110amino acid zwitterion;
glutamic acid derivative;
hydroxamic acid
leucine hydroxamate
leucine hydroxamate: RN given refers to (S)-isomer		2.0110
dizocilpine maleate
Dizocilpine Maleate: A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.. dizocilpine maleate : A maleate salt obtained by reaction of dizocilpine with one equivalent of maleic acid.		2.0610maleate salt;
tetracyclic antidepressant		anaesthetic;
anticonvulsant;
neuroprotective agent;
nicotinic antagonist;
NMDA receptor antagonist
phenobarbital sodium
2-(phosphonomethyl)pentanedioic acid: an N-acetylated alpha-linked acidic dipeptidase (NAALADase) antagonist		4.5270
ly 341495
LY 341495: structure in first source		2.7330
ConditionIndicatedRelationship StrengthStudiesTrials
Constriction, Pathological
[description not available]		02.9540
Allodynia
[description not available]		02.4420
Ache
[description not available]		03.1350
Peripheral Nerve Diseases
[description not available]		02.9540
Constriction, Pathologic
The condition of an anatomical structure's being constricted beyond normal dimensions.		02.9540
Pain
An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.		03.1350
Peripheral Nervous System Diseases
Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.		02.9540
Cerebral Ischemia
[description not available]		02.4220
Brain Ischemia
Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.		02.4220
Cerebral Infarction, Middle Cerebral Artery
[description not available]		02.0210
Infarction, Middle Cerebral Artery
NECROSIS occurring in the MIDDLE CEREBRAL ARTERY distribution system which brings blood to the entire lateral aspects of each CEREBRAL HEMISPHERE. Clinical signs include impaired cognition; APHASIA; AGRAPHIA; weak and numbness in the face and arms, contralaterally or bilaterally depending on the infarction.		02.0210
Chronic Illness
[description not available]		02.0310
Chronic Disease
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).		02.0310
Nerve Pain
[description not available]		02.7830
Neuralgia
Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.		02.7830
Anoxia-Ischemia, Brain
[description not available]		02.3110
Hypoxia-Ischemia, Brain
A disorder characterized by a reduction of oxygen in the blood combined with reduced blood flow (ISCHEMIA) to the brain from a localized obstruction of a cerebral artery or from systemic hypoperfusion. Prolonged hypoxia-ischemia is associated with ISCHEMIC ATTACK, TRANSIENT; BRAIN INFARCTION; BRAIN EDEMA; COMA; and other conditions.		02.3110
Degenerative Diseases, Central Nervous System
[description not available]		02.110
Neurodegenerative Diseases
Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.		02.110
Cocaine Abuse
[description not available]		02.0510
Cocaine-Related Disorders
Disorders related or resulting from use of cocaine.		02.0510
Dementia Praecox
[description not available]		02.0610
Schizophrenia
A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.		02.0610
Cholera Infantum
[description not available]		03.4111
Asymmetric Diabetic Proximal Motor Neuropathy
[description not available]		02.0310
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.0310
Diabetic Neuropathies
Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)		02.0310