Compounds > (alpha-carboxycyclopropyl)glycine, (1r-(1alpha(s*),2alpha))-isomer
Page last updated: 2024-12-10

(alpha-carboxycyclopropyl)glycine, (1r-(1alpha(s*),2alpha))-isomer

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## (1R-(1α(S*),2α))-(α-Carboxycyclopropyl)glycine: A Powerful Tool for Biological Research

**(1R-(1α(S*),2α))-(α-Carboxycyclopropyl)glycine**, also known as **(α-carboxycyclopropyl)glycine (CCG)**, is a unique and potent amino acid analog. Its significance lies in its ability to act as a **non-hydrolyzable analog of glutamate**, a crucial neurotransmitter in the central nervous system.

**Key Features:**

* **Non-hydrolyzable:** Unlike glutamate, CCG cannot be broken down by the enzymes responsible for glutamate degradation. This allows for sustained activity at glutamate receptors.
* **Selective for NMDA receptors:** CCG exhibits high affinity for the NMDA receptor subtype, a key player in synaptic plasticity, learning, and memory.
* **Stereospecific:** The specific stereoisomer (1R-(1α(S*),2α)) is crucial for its biological activity. Other isomers might have different or no effects.

**Research Importance:**

* **Understanding NMDA Receptor Function:** CCG serves as a powerful tool for investigating the role of NMDA receptors in various biological processes, including:
* **Synaptic plasticity:** CCG can induce long-term potentiation (LTP), a key mechanism for learning and memory.
* **Neurotoxicity:** Overactivation of NMDA receptors can lead to neuronal death, a process implicated in neurodegenerative disorders.
* **Drug development:** CCG can be used to study the effects of potential NMDA receptor modulators, leading to the development of novel therapies for neurological conditions.
* **Probing Glutamate Metabolism:** The non-hydrolyzable nature of CCG allows researchers to dissect the role of glutamate metabolism in various physiological processes, such as:
* **Neurotransmission:** By blocking glutamate degradation, CCG can help elucidate the dynamics of glutamate signaling.
* **Astrocyte function:** Astrocytes are critical for glutamate uptake and recycling. CCG can be used to investigate the impact of altered glutamate metabolism on astrocytic activity.

**Limitations:**

* **Toxicity:** High doses of CCG can be neurotoxic, highlighting the importance of careful dose control in research studies.
* **Limited penetration:** CCG has limited ability to cross the blood-brain barrier, potentially limiting its in vivo applications.

**Overall, (1R-(1α(S*),2α))-(α-Carboxycyclopropyl)glycine is a valuable research tool providing insights into the complex functions of NMDA receptors and glutamate metabolism. Its applications are likely to expand further as research progresses, contributing to our understanding of neurological disorders and potential therapeutic strategies.**

Cross-References

ID SourceID
PubMed CID5310958
CHEMBL ID282842
SCHEMBL ID9078498
MeSH IDM0320316

Synonyms (20)

Synonym
tocris-0333
NCGC00024541-01
tocris-0332
NCGC00024540-01
l-ccg-iv
CHEMBL282842 ,
SCHEMBL9078498
2-(amino-carboxy-methyl)-cyclopropanecarboxylic acid (d-cga-c)
bdbm50220152
(1s,2r)-2-((s)-amino(carboxy)methyl)cyclopropanecarboxylic acid
(1s,2r)-2-((s)-amino-carboxy-methyl)-cyclopropanecarboxylic acid
(2s,3r,4s)-ccg
DTXSID00415498
117857-96-2
J-003678
(2s,3r,4s)-alpha-(carboxycyclopropyl)glycine, solid
(2s,3r,4s)-alpha-(carboxycyclopropyl)glycine
(1s,2r)-2-[(s)-amino(carboxy)methyl]cyclopropane-1-carboxylic acid
BL168614
(1s,2r)-2-((s)-amino(carboxy)methyl)cyclopropane-1-carboxylic acid
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (10)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, 2-oxoglutarate OxygenaseHomo sapiens (human)Potency35.48130.177814.390939.8107AID2147
phosphopantetheinyl transferaseBacillus subtilisPotency89.12510.141337.9142100.0000AID1490
muscarinic acetylcholine receptor M1Rattus norvegicus (Norway rat)Potency0.03980.00106.000935.4813AID943
[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)
Glutamate receptor ionotropic, NMDA 1 Rattus norvegicus (Norway rat)Ki0.00900.00030.86666.6900AID298026
Glutamate receptor ionotropic, NMDA 2A Rattus norvegicus (Norway rat)Ki0.00900.00030.68056.6900AID298026
Glutamate receptor ionotropic, NMDA 2BRattus norvegicus (Norway rat)Ki0.00900.00030.70716.6900AID298026
Glutamate receptor ionotropic, NMDA 2CRattus norvegicus (Norway rat)Ki0.00900.00030.81966.6900AID298026
Glutamate receptor ionotropic, NMDA 2DRattus norvegicus (Norway rat)Ki0.00900.00030.70726.6900AID298026
Glutamate receptor ionotropic, NMDA 3BRattus norvegicus (Norway rat)Ki0.00900.00030.70726.6900AID298026
Glutamate receptor ionotropic, NMDA 3ARattus norvegicus (Norway rat)Ki0.00900.00030.70726.6900AID298026
[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 receptor ionotropic, NMDA 1 Rattus norvegicus (Norway rat)EC50 (µMol)0.12020.00301.29038.3000AID739720; AID739721; AID739722; AID739723
Glutamate receptor ionotropic, NMDA 2A Rattus norvegicus (Norway rat)EC50 (µMol)0.18600.00301.02226.8600AID739721; AID739722
Glutamate receptor ionotropic, NMDA 2BRattus norvegicus (Norway rat)EC50 (µMol)0.09650.00300.86696.8600AID739721; AID739723
Glutamate receptor ionotropic, NMDA 2CRattus norvegicus (Norway rat)EC50 (µMol)0.11000.00301.11276.8600AID739721
Glutamate receptor ionotropic, NMDA 2DRattus norvegicus (Norway rat)EC50 (µMol)0.07300.00301.39378.3000AID739720; AID739721
Glutamate receptor ionotropic, NMDA 3BRattus norvegicus (Norway rat)EC50 (µMol)0.11000.00300.90516.8600AID739721
Glutamate receptor ionotropic, NMDA 3ARattus norvegicus (Norway rat)EC50 (µMol)0.11000.00300.90516.8600AID739721
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 1 Rattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 1 Rattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 2A Rattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 2A Rattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 2BRattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 2BRattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 2CRattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 2CRattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 2DRattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 2DRattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 3BRattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 3BRattus norvegicus (Norway rat)
endoplasmic reticulum membraneGlutamate receptor ionotropic, NMDA 3ARattus norvegicus (Norway rat)
plasma membraneGlutamate receptor ionotropic, NMDA 3ARattus norvegicus (Norway rat)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (20)

Assay IDTitleYearJournalArticle
AID739722Agonist activity at rat recombinant wild type GluN1/GluN2A receptor expressed in Xenopus laevis oocytes by two electrode voltage clamp technique2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists.
AID26367pKa value by 1H NMR titration experiments; pK31996Journal of medicinal chemistry, Jan-19, Volume: 39, Issue:2
Syntheses and conformational analyses of glutamate analogs: 2-(2-carboxy-3-substituted-cyclopropyl)glycines as useful probes for excitatory amino acid receptors.
AID739716Ratio of compound Imax to glutamate Imax for rat recombinant wild type GluN1/GluN2D receptor2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists.
AID739717Ratio of compound Imax to glutamate Imax for rat recombinant wild type GluN1/GluN2C receptor2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists.
AID739718Ratio of compound Imax to glutamate Imax for rat recombinant wild type GluN1/GluN2B receptor2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists.
AID144456Displacement of [3H]CPP from N-methyl-D-aspartate glutamate receptor in rat brain membrane1992Journal of medicinal chemistry, Apr-17, Volume: 35, Issue:8
Generation of N-methyl-D-aspartate agonist and competitive antagonist pharmacophore models. Design and synthesis of phosphonoalkyl-substituted tetrahydroisoquinolines as novel antagonists.
AID739720Agonist activity at rat recombinant wild type GluN1/GluN2D receptor expressed in Xenopus laevis oocytes by two electrode voltage clamp technique2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists.
AID739721Agonist activity at rat recombinant wild type GluN1/GluN2C receptor expressed in Xenopus laevis oocytes by two electrode voltage clamp technique2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists.
AID739723Agonist activity at rat recombinant wild type GluN1/GluN2B receptor expressed in Xenopus laevis oocytes by two electrode voltage clamp technique2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists.
AID26366pKa value by 1H NMR titration experiments; pK21996Journal of medicinal chemistry, Jan-19, Volume: 39, Issue:2
Syntheses and conformational analyses of glutamate analogs: 2-(2-carboxy-3-substituted-cyclopropyl)glycines as useful probes for excitatory amino acid receptors.
AID739719Ratio of compound Imax to glutamate Imax for rat recombinant wild type GluN1/GluN2A receptor2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists.
AID739724Displacement of [3H]CGP39653 from NMDA receptor in rat cortical synaptosomes2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists.
AID196268Depolarizing potency in new born rat spinal cord1996Journal of medicinal chemistry, Jan-19, Volume: 39, Issue:2
Syntheses and conformational analyses of glutamate analogs: 2-(2-carboxy-3-substituted-cyclopropyl)glycines as useful probes for excitatory amino acid receptors.
AID739725Displacement of [3H]KA from KA receptor in rat cortical synaptosomes2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists.
AID298026Displacement of [3H]CGP-39653 from rat NMDA receptor expressed in BHK cells2007Journal of medicinal chemistry, Sep-20, Volume: 50, Issue:19
Synthesis, molecular modeling studies, and preliminary pharmacological characterization of all possible 2-(2'-sulfonocyclopropyl)glycine stereoisomers as conformationally constrained L-homocysteic acid analogs.
AID26365pKa value by 1H NMR titration experiments; pK11996Journal of medicinal chemistry, Jan-19, Volume: 39, Issue:2
Syntheses and conformational analyses of glutamate analogs: 2-(2-carboxy-3-substituted-cyclopropyl)glycines as useful probes for excitatory amino acid receptors.
AID91444Depolarizing potency in Ionotropic glutamate receptor kainate sensitive neurons in the immature rat dorsal roots1996Journal of medicinal chemistry, Jan-19, Volume: 39, Issue:2
Syntheses and conformational analyses of glutamate analogs: 2-(2-carboxy-3-substituted-cyclopropyl)glycines as useful probes for excitatory amino acid receptors.
AID739726Displacement of [3H]AMPA from AMPA receptor in rat cortical synaptosomes2013Journal of medicinal chemistry, May-23, Volume: 56, Issue:10
Development of 2'-substituted (2S,1'R,2'S)-2-(carboxycyclopropyl)glycine analogues as potent N-methyl-d-aspartic acid receptor agonists.
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.
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.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (6)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's2 (33.33)18.2507
2000's1 (16.67)29.6817
2010's1 (16.67)24.3611
2020's2 (33.33)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 12.85

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 Index12.85 (24.57)
Research Supply Index1.95 (2.92)
Research Growth Index4.80 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (12.85)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other6 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
2-aminoadipic acid
2-Aminoadipic Acid: A metabolite in the principal biochemical pathway of lysine. It antagonizes neuroexcitatory activity modulated by the glutamate receptor, N-METHYL-D-ASPARTATE; (NMDA).. 2-aminoadipic acid : An alpha-amino acid that is adipic acid bearing a single amino substituent at position 2. An intermediate in the formation of lysine.		1.9810amino dicarboxylic acid;
dicarboxylic fatty acid;
non-proteinogenic alpha-amino acid		Caenorhabditis elegans metabolite;
mammalian metabolite
quinolinic acid
Quinolinic Acid: A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are correlated with the severity of neuropsychological deficits in patients who have AIDS.. pyridinedicarboxylic acid : Any member of the class of pyridines carrying two carboxy groups.. quinolinic acid : A pyridinedicarboxylic acid that is pyridine substituted by carboxy groups at positions 2 and 3. It is a metabolite of tryptophan.		1.9810pyridinedicarboxylic acidEscherichia coli metabolite;
human metabolite;
mouse metabolite;
NMDA receptor agonist
2-amino-5-phosphonovalerate
2-Amino-5-phosphonovalerate: The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.		1.9810non-proteinogenic alpha-amino acidNMDA receptor antagonist
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid: An IBOTENIC ACID homolog and glutamate agonist. The compound is the defining agonist for the AMPA subtype of glutamate receptors (RECEPTORS, AMPA). It has been used as a radionuclide imaging agent but is more commonly used as an experimental tool in cell biological studies.		1.9910non-proteinogenic alpha-amino acid
3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid: structure given in first source; NMDA receptor antagonist		1.9810
ibotenic acid
Ibotenic Acid: A neurotoxic isoxazole (similar to KAINIC ACID and MUSCIMOL) found in AMANITA mushrooms. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist.		1.9810non-proteinogenic alpha-amino acidneurotoxin
2-amino-4-phosphonobutyric acid
2-amino-4-phosphonobutyric acid: glutamate antagonist in locust muscle; structure; do not confuse with L-AP4, which is the propionic acid version		1.9810
2-amino-6-phosphonohexanoic acid
2-amino-6-phosphonohexanoic acid: RN given refers to DL-isomer		1.9810
2-amino-7-phosphonoheptanoic acid
2-amino-7-phosphonoheptanoic acid: (D)-isomer active as an antagonist of N-methyl-D-aspartate excitation of central neurons; (L)-isomer inactive; RN given refers to cpd without isomeric designation		1.9810
aspartic acid
Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.. aspartic acid : An alpha-amino acid that consists of succinic acid bearing a single alpha-amino substituent. L-aspartic acid : The L-enantiomer of aspartic acid.		1.9810aspartate family amino acid;
aspartic acid;
L-alpha-amino acid;
proteinogenic amino acid		Escherichia coli metabolite;
mouse metabolite;
neurotransmitter
kainic acid
Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.		1.9910dicarboxylic acid;
L-proline derivative;
non-proteinogenic L-alpha-amino acid;
pyrrolidinecarboxylic acid		antinematodal drug;
excitatory amino acid agonist
glutamic acid
Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.. glutamic acid : An alpha-amino acid that is glutaric acid bearing a single amino substituent at position 2.		2.6930glutamic acid;
glutamine family amino acid;
L-alpha-amino acid;
proteinogenic amino acid		Escherichia coli metabolite;
ferroptosis inducer;
micronutrient;
mouse metabolite;
neurotransmitter;
nutraceutical
selfotel
selfotel: a N-methyl-D-aspartate (NMDA) antagonist; used to treat stroke-induced impairment		1.9810non-proteinogenic alpha-amino acid
d-aspartic acid
[no description available]		1.9810aspartic acid;
D-alpha-amino acid		mouse metabolite
alpha-amino-3-(hydroxy)-5-methyl-4-isoxazoleacetic acid
alpha-amino-3-(hydroxy)-5-methyl-4-isoxazoleacetic acid: RN given refers to cpd without isomeric designation; structure given in first source		1.9810
homocysteic acid
homocysteic acid: promotes growth in hypophysectomized rats; RN given refers to parent cpd. homocysteic acid : A non-proteinogenic alpha-amino acid that is homocysteine in which the thiol group has benn oxidised to the corresponding sulfonic acid.. L-homocysteic acid : A homocysteic acid with L-configuration.		2.0310homocysteic acidNMDA receptor agonist
alpha,alpha'-diaminosuberic acid
alpha,alpha'-diaminosuberic acid: RN given refers to cpd with unspecified isomeric designation		1.9810
homoquinolinic acid
homoquinolinic acid: structure given in first source		1.9810
l-2-(carboxypropyl)glycine
[no description available]		1.9910
l-ccg iii
[no description available]		2.3920
cgp 37849
2-amino-4-methyl-5-phosphono-3-pentenoic acid: N-methyl-D-aspartate receptor antagonist; structure given in first source; RN given refers to cpd without isomeric designation; CGP-40116 is the (R)-enantiomer of CGP-37849; CGP-40017 is the L-isomer		1.9810
1-amino-1,3-dicarboxycyclopentane, cis-(1s,3s)-isomer
[no description available]		1.9810
ConditionIndicatedRelationship StrengthStudiesTrials
Congenital Zika Syndrome
[description not available]		02.2510
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.2510
Zika Virus Infection
A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.		02.2510