Page last updated: 2024-12-05

gabaculine

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

Description

Gabaculine is a potent and selective inhibitor of GABA transaminase, the enzyme responsible for the degradation of GABA in the brain. It was first synthesized in the 1970s and has been extensively studied for its effects on GABAergic neurotransmission. Gabaculine increases GABA levels in the brain, leading to enhanced GABAergic activity. This can result in various effects, including sedation, anxiolysis, and anticonvulsant activity. Researchers are interested in gabaculine due to its potential therapeutic applications in conditions such as epilepsy, anxiety disorders, and neuropathic pain. Gabaculine has been used as a research tool to investigate the role of GABA in various neurological processes, and it has also been explored as a potential drug candidate. However, gabaculine has also been shown to have neurotoxic effects at high doses, and its clinical development has been limited. The synthesis of gabaculine involves a multi-step process starting from readily available starting materials. It is a structurally unique compound that has served as a valuable probe in the study of GABAergic neurotransmission.'

gabaculine: potent inhibitor of aminobutyrate aminotransferase from Streptomyces toyocaensis.; also inhibits a variety of PLP-dependent aminotransferases; structure; RN given refers to cpd without isomeric designation [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

(S)-gabaculine : The (S)-enantiomer of gabaculine. [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]

5-aminocyclohexa-1,3-diene-1-carboxylic acid : An alpha,beta-unsaturated monocarboxylic acid that is cyclohexa-1,3-diene-1-carboxylic acid carrying an amino group at position 5. [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 CID173685
CHEMBL ID1474486
CHEBI ID145084
SCHEMBL ID17742871
MeSH IDM0060407
PubMed CID3445
CHEMBL ID1394922
CHEBI ID29585
SCHEMBL ID2024044
MeSH IDM0060407

Synonyms (65)

Synonym
(-)-5-amino-1,3-cyclohexadiene-1-carboxylic acid
708-b
1,3-cyclohexadiene-1-carboxylic acid, 5-amino-, (-)-
brn 4662689
gabaculin
lopac-a-3539
NCGC00015051-01
gabaculine
(s)-5-amino-1,3-cyclohexadiene-1-carboxylic acid
[s,(-)]-5-amino-1,3-cyclohexadiene-1-carboxylic acid
(-)-gabaculine
59556-29-5
(5s)-5-aminocyclohexa-1,3-diene-1-carboxylic acid
(s)-gabaculine
CHEBI:145084
AKOS006341852
unii-3f3enu341o
1,3-cyclohexadiene-1-carboxylic acid, 5-amino-, (s)-
3f3enu341o ,
CHEMBL1474486
1,3-cyclohexadiene-1-carboxylic acid, 5-amino-, (5s)-
(5s)-5-amino-1,3-cyclohexadiene-1-carboxylic acid
DTXSID70208233
SCHEMBL17742871
(s)-5-aminocyclohexa-1,3-diene-1-carboxylic acid
5-aminocyclohexa-1,3-diene-1-carboxylic acid
gabaculine, d.l-
nsc-329502
nsc329502
dl-gabaculine
59556-18-2
BIOMOL-NT_000232
BPBIO1_000639
3-amino-2,3-dihydrobenzoic acid
87980-11-8
NCGC00162040-02
5-amino-1,3-cyclohexadienylcarboxylic acid
LOPAC0_000006
NCGC00162040-01
CPD0-1467 ,
9755169F-ECDB-4A93-87CD-F7B81C176DAE
benzoic acid, 3-amino-2,3-dihydro-
NCGC00015051-04
CCG-204102
NCGC00015051-02
NCGC00015051-03
CHEMBL1394922
SCHEMBL2024044
5-amino-1,3-cyclohexadiene-1-carboxylic acid
CHEBI:29585
5-amino-1,3-cyclohexadiene-1-carboxylic acid #
KFNRJXCQEJIBER-UHFFFAOYSA-N
(+-)-gabaculine
nsc 329502
3-amino-4,6-cyclohexadienecarboxylic acid
DTXSID90274399
DTXSID50868990
Q1007138
SDCCGSBI-0049995.P002
NCGC00015051-05
3-amino-4,6-cyclohexadienecarboxylicacid
1,3-cyclohexadiene-1-carboxylicacid,5-amino-(9ci)
(+/-)-gabaculine
ZK7T58839G
gabaculine, (+/-)-

Research Excerpts

Dosage Studied

ExcerptRelevanceReference
" The relationship held over an extensive range of experimental conditions including different drugs, different dosage levels of the same drug, different time intervals after administration of the same drug, and both single and multiple injections of drugs."( Regulation of the GABAA receptor/ion channel complex by intracellular GABA levels.
Davies, M; Wood, JD, 1991
)
0.28
" Dopa accumulation was significantly inhibited at a high dosage by nipecotic acid alone and by low dosages of nipecotic acid in rats pretreated with either aminooxyacetic acid or gabaculine."( Use of gamma-aminobutyric acid (GABA)-transaminase inhibitors and a GABA uptake inhibitor to investigate the influence of GABA neurons on dopamine-containing amacrine cells of the rat retina.
Morgan, WW; Proll, MA, 1983
)
0.27
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
bacterial metaboliteAny prokaryotic metabolite produced during a metabolic reaction in bacteria.
EC 2.6.1.19 (4-aminobutyrate--2-oxoglutarate transaminase) inhibitorAn EC 2.6.1.* (transaminase) inhibitor that interferes with the action of 4-aminobutyrate--2-oxoglutarate transaminase (EC 2.6.1.19).
[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 (3)

ClassDescription
5-aminocyclohexa-1,3-diene-1-carboxylic acidAn alpha,beta-unsaturated monocarboxylic acid that is cyclohexa-1,3-diene-1-carboxylic acid carrying an amino group at position 5.
gamma-amino acidA non-proteinogenic amino-acid in which the amino group is located on the carbon atom at the position gamma to the carboxy group.
alpha,beta-unsaturated monocarboxylic acidA monocarboxylic acid in which the carbon of the carboxy group is directly attached to a C=C or C#C bond.
[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 (14)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, HADH2 proteinHomo sapiens (human)Potency25.11890.025120.237639.8107AID886
Chain B, HADH2 proteinHomo sapiens (human)Potency25.11890.025120.237639.8107AID886
thyroid stimulating hormone receptorHomo sapiens (human)Potency3.98110.001318.074339.8107AID926
mitogen-activated protein kinase 1Homo sapiens (human)Potency0.00630.039816.784239.8107AID995
muscarinic acetylcholine receptor M1Rattus norvegicus (Norway rat)Potency5.01190.00106.000935.4813AID944
Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASEHomo sapiens (human)Potency12.58930.003245.467312,589.2998AID2517
Chain A, TYROSYL-DNA PHOSPHODIESTERASEHomo sapiens (human)Potency2.55160.004023.8416100.0000AID485290; AID489007
thioredoxin reductaseRattus norvegicus (Norway rat)Potency2.23870.100020.879379.4328AID588453
ATAD5 protein, partialHomo sapiens (human)Potency1.45750.004110.890331.5287AID493106
GLS proteinHomo sapiens (human)Potency31.62280.35487.935539.8107AID624146
regulator of G-protein signaling 4Homo sapiens (human)Potency0.94570.531815.435837.6858AID504845
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency2.37780.035520.977089.1251AID504332
DNA polymerase kappa isoform 1Homo sapiens (human)Potency10.00000.031622.3146100.0000AID588579
histone acetyltransferase KAT2A isoform 1Homo sapiens (human)Potency35.48130.251215.843239.8107AID504327
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (20)

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.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347050Natriuretic polypeptide receptor (hNpr2) antagonism - Pilot subtype selectivity assay2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID588378qHTS for Inhibitors of ATXN expression: Validation
AID1347049Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot screen2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347057CD47-SIRPalpha protein protein interaction - LANCE assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347045Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot counterscreen GloSensor control cell line2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID588349qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347410qHTS for inhibitors of adenylyl cyclases using a fission yeast platform: a pilot screen against the NCATS LOPAC library2019Cellular signalling, 08, Volume: 60A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.
AID1347058CD47-SIRPalpha protein protein interaction - HTRF assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347405qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS LOPAC collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID504836Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation2002The Journal of biological chemistry, Apr-19, Volume: 277, Issue:16
Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells.
AID1347151Optimization of GU AMC qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings 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.
AID1347059CD47-SIRPalpha protein protein interaction - Alpha assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
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 (140)

TimeframeStudies, This Drug (%)All Drugs %
pre-199058 (41.43)18.7374
1990's45 (32.14)18.2507
2000's12 (8.57)29.6817
2010's17 (12.14)24.3611
2020's8 (5.71)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 28.33

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 moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index28.33 (24.57)
Research Supply Index2.48 (2.92)
Research Growth Index5.03 (4.65)
Search Engine Demand Index31.58 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (28.33)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (0.76%)5.53%
Trials0 (0.00%)5.53%
Reviews1 (0.76%)6.00%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Observational0 (0.00%)0.25%
Other130 (98.48%)84.16%
Other11 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]