Page last updated: 2024-09-27

ci 966

Description

CI 966: GABA uptake blocker; RN from Toxlit [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID198693
CHEMBL ID77287
CHEMBL ID542207
CHEBI ID93185
SCHEMBL ID7927078
MeSH IDM0183787

Synonyms (30)

Synonym
CHEMBL77287 ,
110283-79-9
unii-4hve799mej
4hve799mej ,
3-pyridinecarboxylic acid, 1-(2-(bis(4-(trifluoromethyl)phenyl)methoxy)ethyl)-1,2,5,6-tetrahydro-
1-(2-(bis(4-(trifluoromethyl)phenyl)methox)ethyl)-1,2,5,6-tetrahydro-3-pyrdinecarboxylic acid
BRD-K67680372-003-01-8
ci 966
NCGC00025099-01
tocris-1296
ci-966
bdbm50003618
1-{2-[bis-(4-trifluoromethyl-phenyl)-methoxy]-ethyl}-1,2,5,6-tetrahydro-pyridine-3-carboxylic acid; hydrochloride
chembl542207 ,
A802236
1-[2-[bis[4-(trifluoromethyl)phenyl]methoxy]ethyl]-3,6-dihydro-2h-pyridine-5-carboxylic acid
3-pyridinecarboxylicacid, 1-[2-[bis[4-(trifluoromethyl)phenyl]methoxy]ethyl]-1,2,5,6-tetrahydro-
1-(2-{bis[4-(trifluoromethyl)phenyl]methoxy}ethyl)-1,2,5,6-tetrahydropyridine-3-carboxylic acid
gtpl4612
AKOS022180213
ci-966 free base
SCHEMBL7927078
DTXSID90149194
sr-01000597733
SR-01000597733-1
CHEBI:93185
1-(2-(bis(4-(trifluoromethyl)phenyl)methoxy)ethyl)-1,2,5,6-tetrahydropyridine-3-carboxylic acid
Q15410874
ci-966 hydrochloride
cmhqdsbibskhfp-uhfffaoysa-n

Drug Classes (1)

ClassDescription
diarylmethaneAny compound containing two aryl groups connected by a single C atom.
[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 (27)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, CruzipainTrypanosoma cruziPotency25.11890.002014.677939.8107AID1476
15-lipoxygenase, partialHomo sapiens (human)Potency15.84890.012610.691788.5700AID887
TDP1 proteinHomo sapiens (human)Potency21.13600.000811.382244.6684AID686979
cytochrome P450 2C9 precursorHomo sapiens (human)Potency2.51190.00636.904339.8107AID883
cytochrome P450 3A4 isoform 1Homo sapiens (human)Potency39.81070.031610.279239.8107AID884; AID885
lethal factor (plasmid)Bacillus anthracis str. A2012Potency12.58930.020010.786931.6228AID912
Gamma-aminobutyric acid receptor subunit piRattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-1Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit deltaRattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-5Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-3Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-1Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-2Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-4Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit gamma-3Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit alpha-6Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Histamine H2 receptorCavia porcellus (domestic guinea pig)Potency2.51190.00638.235039.8107AID883
Gamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-3Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
GABA theta subunitRattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
Gamma-aminobutyric acid receptor subunit epsilonRattus norvegicus (Norway rat)Potency39.81071.000012.224831.6228AID885
[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)
Sodium- and chloride-dependent GABA transporter 1Homo sapiens (human)IC50 (µMol)0.26000.01013.090310.0000AID205303
Sodium- and chloride-dependent GABA transporter 2Rattus norvegicus (Norway rat)IC50 (µMol)1,280.00000.00321.79008.3000AID205447
Sodium- and chloride-dependent betaine transporterHomo sapiens (human)IC50 (µMol)300.00000.85116.052136.0000AID205304
Sodium- and chloride-dependent GABA transporter 3Homo sapiens (human)IC50 (µMol)333.00001.00004.13318.9200AID72446
[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)
Sodium- and chloride-dependent GABA transporter 1Homo sapiens (human)INH0.26000.04000.12330.2600AID774377
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (28)

Processvia Protein(s)Taxonomy
memorySodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
associative learningSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
synapse organizationSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
chemical synaptic transmissionSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
response to toxic substanceSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
response to sucroseSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
response to inorganic substanceSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
response to lead ionSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
positive regulation of gamma-aminobutyric acid secretionSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
response to purine-containing compoundSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
negative regulation of synaptic transmission, GABAergicSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
response to estradiolSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
response to cocaineSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
response to calcium ionSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
gamma-aminobutyric acid reuptakeSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
gamma-aminobutyric acid importSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
inorganic anion import across plasma membraneSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
sodium ion import across plasma membraneSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
transport across blood-brain barrierSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
chloride transmembrane transportSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
sodium ion transmembrane transportSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
amino acid transportSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
amino acid transmembrane transportSodium- and chloride-dependent betaine transporterHomo sapiens (human)
amino acid transportSodium- and chloride-dependent betaine transporterHomo sapiens (human)
monocarboxylic acid transportSodium- and chloride-dependent betaine transporterHomo sapiens (human)
gamma-aminobutyric acid transportSodium- and chloride-dependent betaine transporterHomo sapiens (human)
glycine betaine transportSodium- and chloride-dependent betaine transporterHomo sapiens (human)
gamma-aminobutyric acid reuptakeSodium- and chloride-dependent betaine transporterHomo sapiens (human)
sodium ion transmembrane transportSodium- and chloride-dependent betaine transporterHomo sapiens (human)
amino acid transmembrane transportSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
response to xenobiotic stimulusSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
monocarboxylic acid transportSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
taurine transmembrane transportSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
gamma-aminobutyric acid reuptakeSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
sodium ion transmembrane transportSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
amino acid transportSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (10)

Processvia Protein(s)Taxonomy
gamma-aminobutyric acid:sodium:chloride symporter activitySodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
protein bindingSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
gamma-aminobutyric acid transmembrane transporter activitySodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
sodium:chloride symporter activitySodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
identical protein bindingSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
metal ion bindingSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
gamma-aminobutyric acid:sodium:chloride symporter activitySodium- and chloride-dependent betaine transporterHomo sapiens (human)
protein bindingSodium- and chloride-dependent betaine transporterHomo sapiens (human)
monocarboxylic acid transmembrane transporter activitySodium- and chloride-dependent betaine transporterHomo sapiens (human)
amino acid transmembrane transporter activitySodium- and chloride-dependent betaine transporterHomo sapiens (human)
gamma-aminobutyric acid:sodium:chloride symporter activitySodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
taurine:sodium symporter activitySodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
monocarboxylic acid transmembrane transporter activitySodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
amino acid bindingSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (11)

Processvia Protein(s)Taxonomy
plasma membraneGamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)
plasma membraneSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
plasma membraneSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
membraneSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
axonSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
presynaptic membraneSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
neuronal cell bodySodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
postsynaptic membraneSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
GABA-ergic synapseSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
axonSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
cell surfaceSodium- and chloride-dependent GABA transporter 1Homo sapiens (human)
plasma membraneSodium- and chloride-dependent betaine transporterHomo sapiens (human)
membraneSodium- and chloride-dependent betaine transporterHomo sapiens (human)
basolateral plasma membraneSodium- and chloride-dependent betaine transporterHomo sapiens (human)
presynapseSodium- and chloride-dependent betaine transporterHomo sapiens (human)
cell projectionSodium- and chloride-dependent betaine transporterHomo sapiens (human)
plasma membraneSodium- and chloride-dependent betaine transporterHomo sapiens (human)
plasma membraneSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
membraneSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
presynaptic membraneSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
postsynaptic membraneSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
GABA-ergic synapseSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
plasma membraneSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
cell projectionSodium- and chloride-dependent GABA transporter 3Homo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (9)

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.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS 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.
AID1346940Human GAT1 (GABA transporter subfamily)1994European journal of pharmacology, Oct-14, Volume: 269, Issue:2
Tiagabine, SK&F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1.
AID72446Inhibitory activity against human sodium and chloride dependent GABA transporter 31994Journal of medicinal chemistry, Jul-22, Volume: 37, Issue:15
Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3.
AID205304Inhibition of human GABA transporter (hBGT-1) activity.1994Journal of medicinal chemistry, Jul-22, Volume: 37, Issue:15
Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3.
AID205303Inhibitory activity against human GABA transporter-1 (hGAT1)1994Journal of medicinal chemistry, Jul-22, Volume: 37, Issue:15
Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3.
AID205447Inhibitory activity against rat GABA transporter-2 (rGAT2)1994Journal of medicinal chemistry, Jul-22, Volume: 37, Issue:15
Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3.
AID774377Inhibition of GAT-1 (unknown origin)2013Journal of natural products, Oct-25, Volume: 76, Issue:10
The lignan (-)-hinokinin displays modulatory effects on human monoamine and GABA transporter activities.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (13)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's8 (61.54)18.2507
2000's1 (7.69)29.6817
2010's1 (7.69)24.3611
2020's3 (23.08)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

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%
Other14 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research Highlights

Pharmacokinetics (1)

ArticleYear
Pharmacokinetics, mass balance, and induction potential of a novel GABA uptake inhibitor, CI-966 HCl, in laboratory animals.
Pharmaceutical research, Volume: 10, Issue: 10
1993
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioavailability (1)

ArticleYear
Pharmacokinetics, mass balance, and induction potential of a novel GABA uptake inhibitor, CI-966 HCl, in laboratory animals.
Pharmaceutical research, Volume: 10, Issue: 10
1993
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Dosage (1)

ArticleYear
Pharmacokinetics, mass balance, and induction potential of a novel GABA uptake inhibitor, CI-966 HCl, in laboratory animals.
Pharmaceutical research, Volume: 10, Issue: 10
1993
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]