L-Glutamic acid (T3D4296)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (76)XML
Targets (76)
Record Information
Version2.0
Creation Date2014-08-29 06:16:44 UTC
Update Date2014-12-24 20:26:45 UTC
Accession NumberT3D4296
Identification
Common NameL-Glutamic acid
ClassSmall Molecule
DescriptionGlutamic acid (Glu), also referred to as glutamate (the anion), is one of the 20 proteinogenic amino acids. It is not among the essential amino acids. Glutamate is a key molecule in cellular metabolism. In humans, dietary proteins are broken down by digestion into amino acids, which serves as metabolic fuel or other functional roles in the body. Glutamate is the most abundant fast excitatory neurotransmitter in the mammalian nervous system. At chemical synapses, glutamate is stored in vesicles. Nerve impulses trigger release of glutamate from the pre-synaptic cell. In the opposing post-synaptic cell, glutamate receptors, such as the NMDA receptor, bind glutamate and are activated. Because of its role in synaptic plasticity, it is believed that glutamic acid is involved in cognitive functions like learning and memory in the brain. Glutamate transporters are found in neuronal and glial membranes. They rapidly remove glutamate from the extracellular space. In brain injury or disease, they can work in reverse and excess glutamate can accumulate outside cells. This process causes calcium ions to enter cells via NMDA receptor channels, leading to neuronal damage and eventual cell death, and is called excitotoxicity. The mechanisms of cell death include: * Damage to mitochondria from excessively high intracellular Ca2+. * Glu/Ca2+-mediated promotion of transcription factors for pro-apoptotic genes, or downregulation of transcription factors for anti-apoptotic genes. Excitotoxicity due to glutamate occurs as part of the ischemic cascade and is associated with stroke and diseases like amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease. glutamic acid has been implicated in epileptic seizures. Microinjection of glutamic acid into neurons produces spontaneous depolarization around one second apart, and this firing pattern is similar to what is known as paroxysmal depolarizing shift in epileptic attacks. This change in the resting membrane potential at seizure foci could cause spontaneous opening of voltage activated calcium channels, leading to glutamic acid release and further depolarization.
Compound Type
  • Amine
  • Animal Toxin
  • Dietary Supplement
  • Drug
  • Food Toxin
  • Household Toxin
  • Metabolite
  • Micronutrient
  • Natural Compound
  • Non-Essential Amino Acid
  • Nutraceutical
  • Organic Compound
  • Supplement
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
(2S)-2-Aminopentanedioate
(2S)-2-Aminopentanedioic acid
(S)-(+)-Glutamate
(S)-(+)-Glutamic acid
(S)-2-Aminopentanedioate
(S)-2-Aminopentanedioic acid
(S)-Glutamate
(S)-Glutamic acid
1-Amino-propane-1,3-dicarboxylate
1-Amino-propane-1,3-dicarboxylic acid
1-Aminopropane-1,3-dicarboxylate
1-Aminopropane-1,3-dicarboxylic acid
2-Aminoglutarate
2-Aminoglutaric acid
2-Aminopentanedioate
2-Aminopentanedioic acid
a-Aminoglutarate
a-Aminoglutaric acid
a-Glutamate
a-Glutamic acid
Aciglut
alpha-Aminoglutarate
alpha-Aminoglutaric acid
alpha-Glutamate
alpha-Glutamic acid
Aminoglutarate
Aminoglutaric acid
E
Glt
Glu
Glusate
Glut
Glutacid
Glutamic acid
Glutamicol
Glutamidex
Glutaminate
Glutaminic acid
Glutaminol
Glutaton
L-(+)-Glutamate
L-(+)-Glutamic acid
L-a-Aminoglutarate
L-a-Aminoglutaric acid
L-alpha-Aminoglutarate
L-alpha-Aminoglutaric acid
L-Glu
L-Glutamate
L-Glutaminate
L-Glutaminic acid
Chemical FormulaC5H9NO4
Average Molecular Mass147.129 g/mol
Monoisotopic Mass147.053 g/mol
CAS Registry Number56-86-0
IUPAC Name(2S)-2-aminopentanedioic acid
Traditional NameL-glutamic acid
SMILES[H][C@](N)(CCC(O)=O)C(O)=O
InChI IdentifierInChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/t3-/m0/s1
InChI KeyInChIKey=WHUUTDBJXJRKMK-VKHMYHEASA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as glutamic acid and derivatives. Glutamic acid and derivatives are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentGlutamic acid and derivatives
Alternative Parents
Substituents
  • Glutamic acid or derivatives
  • Alpha-amino acid
  • L-alpha-amino acid
  • Amino fatty acid
  • Dicarboxylic acid or derivatives
  • Fatty acid
  • Fatty acyl
  • Amino acid
  • Carboxylic acid
  • Organic oxide
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Organopnictogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Amine
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Endoplasmic reticulum
  • Extracellular
  • Lysosome
  • Membrane
  • Mitochondria
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Adrenal Medulla
  • Epidermis
  • Fibroblasts
  • Intestine
  • Kidney
  • Muscle
  • Myelin
  • Nerve Cells
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Stratum Corneum
Pathways
NameSMPDB LinkKEGG Link
Alanine MetabolismSMP00055 map00250
Amino Sugar MetabolismSMP00045 map00520
Ammonia RecyclingSMP00009 map00910
Arginine and Proline MetabolismSMP00020 map00330
Cysteine MetabolismSMP00013 map00270
Folate MetabolismSMP00053 map00670
Glucose-Alanine CycleSMP00127 Not Available
Glutamate MetabolismSMP00072 map00250
Glutathione MetabolismSMP00015 map00480
Glycine and Serine MetabolismSMP00004 map00260
Histidine MetabolismSMP00044 map00340
Malate-Aspartate ShuttleSMP00129 Not Available
Transcription/TranslationSMP00019 Not Available
Urea CycleSMP00059 Not Available
Argininosuccinic AciduriaSMP00003 Not Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point224 dec°C
Boiling PointNot Available
Solubility8570 mg/L (at 25°C)
LogP-3.69
Predicted Properties
PropertyValueSource
Water Solubility80.6 g/LALOGPS
logP-3.5ALOGPS
logP-3.2ChemAxon
logS-0.26ALOGPS
pKa (Strongest Acidic)1.88ChemAxon
pKa (Strongest Basic)9.54ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area100.62 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity31.29 m³·mol⁻¹ChemAxon
Polarizability13.32 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-0002-2950000000-2d6edc93ec5f8dee22232014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-002b-0940000000-4e285988bc537825d94d2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-00dj-9630000000-1ecc76aab862838921392014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-001i-8910000000-00f65ced0c55aa4ad1692014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-0032-3980000000-3069de5b6c49e41769682014-06-16View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0002-0790000000-79d3e289c22cb183faa12017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-0002-2950000000-2d6edc93ec5f8dee22232017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-002b-0940000000-4e285988bc537825d94d2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-QQ (Non-derivatized)splash10-00ea-6932100000-30d3f5dcc198a5971e962017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00dj-9630000000-1ecc76aab862838921392017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-001i-8910000000-00f65ced0c55aa4ad1692017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0032-3980000000-3069de5b6c49e41769682017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0znc-9300000000-f88e86b78a4cee99a2d42016-09-22View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00di-8290000000-f99e03763f636e5578872017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_2_4) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, PositiveNot Available2021-11-05View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_2_1) - 70eV, PositiveNot Available2021-11-05View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-003r-6900000000-95b0a084dc076f9c7b912012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-001i-9000000000-c37d4c80a14ec029ef632012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0a59-9000000000-6f1888aa71bcb0adf76c2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004j-0900000000-5fa8a338dcd2f2a6bdd22012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004i-0900000000-16763200aa07f7629ad42012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-03di-3900000000-d9cfc5187aa799f6f9782012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0a4i-0900000000-10ee9a593e13550bec1c2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0002-0900000000-4d045a3c1fc6e56f801b2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-001i-9000000000-c3c7f8f3754109a0c25b2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004i-0900000000-48bfae26c69408b7f0ae2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0002-0900000000-82c2a681e7522a7bb1d12012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-0002-0905010000-af1c9ec4d0062fa6960e2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-01q9-9700000000-2b967b896a6e489145122012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-004i-0900000000-1434321646181ea894a02012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-00di-0900000000-11fadb2530828eedad8a2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-006t-0941100000-07d051890cb1d9e5c8562012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-004i-9200000000-f8619d11f1f54d836bb12012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-004i-0900000000-ea2dd00e79ef06e8dc042012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Negativesplash10-00di-0900000000-3e239d4014c95a2ef8732012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-0002-0900000000-b548959edce39d319cf42012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-0udi-0900000000-40d901f655797db2cd0f2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-0udi-1900000000-f997527a39900ac431c72012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-0udi-7900000000-60816f0601a4e6d25ffb2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-0007-9000000000-6ee821f657c604d1afca2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-000t-0900000000-7c02624abe56da9247a22012-08-31View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR13C NMR Spectrum (1D, 125 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
2D NMR[1H, 1H]-TOCSY. Unexported temporarily by An Chi on Oct 15, 2021 until json or nmrML file is generated. 2D NMR Spectrum (experimental)Not Available2012-12-04View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
Toxicity Profile
Route of ExposureAbsorbed from the lumen of the small intestine into the enterocytes.Absorption is efficient and occurs by an active transport mechanism.
Mechanism of ToxicityGlutamate activates both ionotropic and metabotropic glutamate receptors. The ionotropic ones being non-NMDA (AMPA and kainate) and NMDA receptors. Free glutamic acid cannot cross the blood-brain barrier in appreciable quantities; instead it is converted into L-glutamine, which the brain uses for fuel and protein synthesis. It is conjectured that glutamate is involved in cognitive functions like learning and memory in the brain, though excessive amounts may cause neuronal damage associated in diseases like amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease. Also, the drug phencyclidine (more commonly known as PCP) antagonizes glutamate at the NMDA receptor, causing behavior reminiscent of schizophrenia. Glutamate in action is extremely difficult to study due to its transient nature.
MetabolismHepatic
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesConsidered to be nature's "Brain food" by improving mental capacities; helps speed the healing of ulcers; gives a "lift" from fatigue; helps control alcoholism, schizophrenia and the craving for sugar.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00142
HMDB IDHMDB00148
PubChem Compound ID33032
ChEMBL IDCHEMBL575060
ChemSpider ID30572
KEGG IDC00025
UniProt IDNot Available
OMIM ID
ChEBI ID16015
BioCyc IDGLT
CTD IDNot Available
Stitch IDNot Available
PDB IDGGL
ACToR IDNot Available
Wikipedia LinkL-Glutamic_Acid
References
Synthesis Reference

Nobuharu Tujimoto, Yoshimi Kikuchi, Osamu Kurahashi, Yoshiko Kawahara, “Mutant Escherichia coli capable of enhanced L-glutamic acid production.” U.S. Patent US5393671, issued August, 1960.

MSDSLink
General References
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  19. Rizzo V, Anesi A, Montalbetti L, Bellantoni G, Trotti R, Melzi d'Eril GV: Reference values of neuroactive amino acids in the cerebrospinal fluid by high-performance liquid chromatography with electrochemical and fluorescence detection. J Chromatogr A. 1996 Apr 5;729(1-2):181-8. [9004939 ]
  20. Agnati LF, Ferre S, Lluis C, Franco R, Fuxe K: Molecular mechanisms and therapeutical implications of intramembrane receptor/receptor interactions among heptahelical receptors with examples from the striatopallidal GABA neurons. Pharmacol Rev. 2003 Sep;55(3):509-50. Epub 2003 Jul 17. [12869660 ]
  21. Rutten EP, Engelen MP, Wouters EF, Schols AM, Deutz NE: Metabolic effects of glutamine and glutamate ingestion in healthy subjects and in persons with chronic obstructive pulmonary disease. Am J Clin Nutr. 2006 Jan;83(1):115-23. [16400059 ]
  22. Agarwal A, Tripathi LM, Pandey VC: Status of ammonia, glutamate, lactate and pyruvate during Plasmodium yoelii infection and pyrimethamine treatment in mice. J Commun Dis. 1997 Sep;29(3):235-41. [9465528 ]
  23. Heuschen UA, Allemeyer EH, Hinz U, Langer K, Heuschen G, Decker-Baumann C, Herfarth C, Stern J: Glutamine distribution in patients with ulcerative colitis and in patients with familial adenomatous polyposis coli before and after restorative proctocolectomy. Int J Colorectal Dis. 2002 Jul;17(4):245-52. Epub 2001 Dec 18. [12073073 ]
  24. Olson RC: A proposed role for nerve growth factor in the etiology of multiple sclerosis. Med Hypotheses. 1998 Dec;51(6):493-8. [10052870 ]
  25. Nakamura K, Matsumura K, Kobayashi S, Kaneko T: Sympathetic premotor neurons mediating thermoregulatory functions. Neurosci Res. 2005 Jan;51(1):1-8. [15596234 ]
  26. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Glutamate receptor 1
General Function:
Pdz domain binding
Specific Function:
Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
Gene Name:
GRIA1
Uniprot ID:
P42261
Molecular Weight:
101505.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1.36 uMNot AvailableBindingDB 17657
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Stein E, Cox JA, Seeburg PH, Verdoorn TA: Complex pharmacological properties of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subtypes. Mol Pharmacol. 1992 Nov;42(5):864-71. [1279377 ]
  4. Henley JM, Jenkins R, Hunt SP: Localisation of glutamate receptor binding sites and mRNAs to the dorsal horn of the rat spinal cord. Neuropharmacology. 1993 Jan;32(1):37-41. [7679210 ]
  5. Li F, Owens N, Verdoorn TA: Functional effects of mutations in the putative agonist binding region of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Mol Pharmacol. 1995 Jan;47(1):148-54. [7838123 ]
  6. Jane DE, Hoo K, Kamboj R, Deverill M, Bleakman D, Mandelzys A: Synthesis of willardiine and 6-azawillardiine analogs: pharmacological characterization on cloned homomeric human AMPA and kainate receptor subtypes. J Med Chem. 1997 Oct 24;40(22):3645-50. [9357531 ]
  7. Baker SR, Bleakman D, Ezquerra J, Ballyk BA, Deverill M, Ho K, Kamboj RK, Collado I, Dominguez C, Escribano A, Mateo AI, Pedregal C, Rubio A: 4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists. Bioorg Med Chem Lett. 2000 Aug 21;10(16):1807-10. [10969973 ]
Target Details
2. Glutamate receptor 2
General Function:
Ionotropic glutamate receptor activity
Specific Function:
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
Gene Name:
GRIA2
Uniprot ID:
P42262
Molecular Weight:
98820.32 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.94 uMNot AvailableBindingDB 17657
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Henley JM, Jenkins R, Hunt SP: Localisation of glutamate receptor binding sites and mRNAs to the dorsal horn of the rat spinal cord. Neuropharmacology. 1993 Jan;32(1):37-41. [7679210 ]
  4. Stein E, Cox JA, Seeburg PH, Verdoorn TA: Complex pharmacological properties of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subtypes. Mol Pharmacol. 1992 Nov;42(5):864-71. [1279377 ]
  5. Li F, Owens N, Verdoorn TA: Functional effects of mutations in the putative agonist binding region of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Mol Pharmacol. 1995 Jan;47(1):148-54. [7838123 ]
  6. Jane DE, Hoo K, Kamboj R, Deverill M, Bleakman D, Mandelzys A: Synthesis of willardiine and 6-azawillardiine analogs: pharmacological characterization on cloned homomeric human AMPA and kainate receptor subtypes. J Med Chem. 1997 Oct 24;40(22):3645-50. [9357531 ]
  7. Baker SR, Bleakman D, Ezquerra J, Ballyk BA, Deverill M, Ho K, Kamboj RK, Collado I, Dominguez C, Escribano A, Mateo AI, Pedregal C, Rubio A: 4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists. Bioorg Med Chem Lett. 2000 Aug 21;10(16):1807-10. [10969973 ]
Target Details
3. Glutamate receptor 4
General Function:
Ionotropic glutamate receptor activity
Specific Function:
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
Gene Name:
GRIA4
Uniprot ID:
P48058
Molecular Weight:
100870.085 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.868 uMNot AvailableBindingDB 17657
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Linden AM, Yu H, Zarrinmayeh H, Wheeler WJ, Skolnick P: Binding of an AMPA receptor potentiator ([3H]LY395153) to native and recombinant AMPA receptors. Neuropharmacology. 2001 Jun;40(8):1010-8. [11406192 ]
  4. Henley JM, Jenkins R, Hunt SP: Localisation of glutamate receptor binding sites and mRNAs to the dorsal horn of the rat spinal cord. Neuropharmacology. 1993 Jan;32(1):37-41. [7679210 ]
  5. Cristovao AJ, Oliveira CR, Carvalho CM: Expression of AMPA/kainate receptors during development of chick embryo retina cells: in vitro versus in vivo studies. Int J Dev Neurosci. 2002 Feb;20(1):1-9. [12008069 ]
  6. Jane DE, Hoo K, Kamboj R, Deverill M, Bleakman D, Mandelzys A: Synthesis of willardiine and 6-azawillardiine analogs: pharmacological characterization on cloned homomeric human AMPA and kainate receptor subtypes. J Med Chem. 1997 Oct 24;40(22):3645-50. [9357531 ]
  7. Baker SR, Bleakman D, Ezquerra J, Ballyk BA, Deverill M, Ho K, Kamboj RK, Collado I, Dominguez C, Escribano A, Mateo AI, Pedregal C, Rubio A: 4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists. Bioorg Med Chem Lett. 2000 Aug 21;10(16):1807-10. [10969973 ]
Target Details
4. Glutamate carboxypeptidase 2
General Function:
Tetrahydrofolyl-poly(glutamate) polymer binding
Specific Function:
Has both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Has a preference for tri-alpha-glutamate peptides. In the intestine, required for the uptake of folate. In the brain, modulates excitatory neurotransmission through the hydrolysis of the neuropeptide, N-aceylaspartylglutamate (NAAG), thereby releasing glutamate. Isoform PSM-4 and isoform PSM-5 would appear to be physiologically irrelevant. Involved in prostate tumor progression.Also exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC.
Gene Name:
FOLH1
Uniprot ID:
Q04609
Molecular Weight:
84330.015 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50428 uMNot AvailableBindingDB 17657
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Rodriguez CE, Lu H, Martinez AR, Hu Y, Brunelle A, Berkman CE: Inhibition of glutamate carboxypeptidase II by phosphonamidothionate derivatives of glutamic acid. J Enzyme Inhib. 2001 Oct;16(4):359-65. [11916141 ]
  4. Davis MI, Bennett MJ, Thomas LM, Bjorkman PJ: Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase. Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):5981-6. Epub 2005 Apr 18. [15837926 ]
  5. Maung J, Mallari JP, Girtsman TA, Wu LY, Rowley JA, Santiago NM, Brunelle AN, Berkman CE: Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates. Bioorg Med Chem. 2004 Sep 15;12(18):4969-79. [15336276 ]
  6. Barinka C, Rovenska M, Mlcochova P, Hlouchova K, Plechanovova A, Majer P, Tsukamoto T, Slusher BS, Konvalinka J, Lubkowski J: Structural insight into the pharmacophore pocket of human glutamate carboxypeptidase II. J Med Chem. 2007 Jul 12;50(14):3267-73. Epub 2007 Jun 14. [17567119 ]
Target Details
5. Glutamate receptor ionotropic, kainate 1
General Function:
Voltage-gated cation channel activity
Specific Function:
Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.
Gene Name:
GRIK1
Uniprot ID:
P39086
Molecular Weight:
103979.665 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.701 uMNot AvailableBindingDB 17657
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Sahara Y, Noro N, Iida Y, Soma K, Nakamura Y: Glutamate receptor subunits GluR5 and KA-2 are coexpressed in rat trigeminal ganglion neurons. J Neurosci. 1997 Sep 1;17(17):6611-20. [9254673 ]
  4. Valgeirsson J, Christensen JK, Kristensen AS, Pickering DS, Nielsen B, Fischer CH, Brauner-Osborne H, Nielsen EO, Krogsgaard-Larsen P, Madsen U: Synthesis and in vitro pharmacology at AMPA and kainate preferring glutamate receptors of 4-heteroarylmethylidene glutamate analogues. Bioorg Med Chem. 2003 Oct 1;11(20):4341-9. [13129570 ]
  5. Stensbol TB, Borre L, Johansen TN, Egebjerg J, Madsen U, Ebert B, Krogsgaard-Larsen P: Resolution, absolute stereochemistry and molecular pharmacology of the enantiomers of ATPA. Eur J Pharmacol. 1999 Sep 10;380(2-3):153-62. [10513575 ]
  6. Baker SR, Bleakman D, Ezquerra J, Ballyk BA, Deverill M, Ho K, Kamboj RK, Collado I, Dominguez C, Escribano A, Mateo AI, Pedregal C, Rubio A: 4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists. Bioorg Med Chem Lett. 2000 Aug 21;10(16):1807-10. [10969973 ]
Target Details
6. Glutamate receptor ionotropic, kainate 3
General Function:
Kainate selective glutamate receptor activity
Specific Function:
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds domoate > kainate >> L-glutamate = quisqualate >> AMPA = NMDA.
Gene Name:
GRIK3
Uniprot ID:
Q13003
Molecular Weight:
104036.06 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.789 uMNot AvailableBindingDB 17657
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Bettler B, Egebjerg J, Sharma G, Pecht G, Hermans-Borgmeyer I, Moll C, Stevens CF, Heinemann S: Cloning of a putative glutamate receptor: a low affinity kainate-binding subunit. Neuron. 1992 Feb;8(2):257-65. [1371217 ]
  4. Takeda M, Haga M, Yamada H, Kinoshita M, Otsuka M, Tsuboi S, Moriyama Y: Ionotropic glutamate receptors expressed in human retinoblastoma Y79 cells. Neurosci Lett. 2000 Nov 17;294(2):97-100. [11058796 ]
  5. Stuhmer T, Amar M, Harvey RJ, Bermudez I, van Minnen J, Darlison MG: Structure and pharmacological properties of a molluscan glutamate-gated cation channel and its likely role in feeding behavior. J Neurosci. 1996 May 1;16(9):2869-80. [8622118 ]
  6. Baker SR, Bleakman D, Ezquerra J, Ballyk BA, Deverill M, Ho K, Kamboj RK, Collado I, Dominguez C, Escribano A, Mateo AI, Pedregal C, Rubio A: 4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists. Bioorg Med Chem Lett. 2000 Aug 21;10(16):1807-10. [10969973 ]
Target Details
7. Glutamate receptor ionotropic, kainate 5
General Function:
Kainate selective glutamate receptor activity
Specific Function:
Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. This receptor binds kainate > quisqualate > domoate > L-glutamate >> AMPA >> NMDA = 1S,3R-ACPD.
Gene Name:
GRIK5
Uniprot ID:
Q16478
Molecular Weight:
109263.695 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.701 uMNot AvailableBindingDB 17657
Inhibitory0.75 uMNot AvailableBindingDB 17657
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Takeda M, Haga M, Yamada H, Kinoshita M, Otsuka M, Tsuboi S, Moriyama Y: Ionotropic glutamate receptors expressed in human retinoblastoma Y79 cells. Neurosci Lett. 2000 Nov 17;294(2):97-100. [11058796 ]
  4. Murphy DE, Hutchison AJ, Hurt SD, Williams M, Sills MA: Characterization of the binding of [3H]-CGS 19755: a novel N-methyl-D-aspartate antagonist with nanomolar affinity in rat brain. Br J Pharmacol. 1988 Nov;95(3):932-8. [2850065 ]
  5. Jane DE, Hoo K, Kamboj R, Deverill M, Bleakman D, Mandelzys A: Synthesis of willardiine and 6-azawillardiine analogs: pharmacological characterization on cloned homomeric human AMPA and kainate receptor subtypes. J Med Chem. 1997 Oct 24;40(22):3645-50. [9357531 ]
  6. Baker SR, Bleakman D, Ezquerra J, Ballyk BA, Deverill M, Ho K, Kamboj RK, Collado I, Dominguez C, Escribano A, Mateo AI, Pedregal C, Rubio A: 4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists. Bioorg Med Chem Lett. 2000 Aug 21;10(16):1807-10. [10969973 ]
Target Details
8. Metabotropic glutamate receptor 1
General Function:
Glutamate receptor activity
Specific Function:
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system. May participate in the central action of glutamate in the CNS, such as long-term potentiation in the hippocampus and long-term depression in the cerebellum.
Gene Name:
GRM1
Uniprot ID:
Q13255
Molecular Weight:
132355.855 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.25 uMNot AvailableBindingDB 17657
Inhibitory0.57 uMNot AvailableBindingDB 17657
Inhibitory10 uMNot AvailableBindingDB 17657
References
  1. Suzuki G, Kimura T, Satow A, Kaneko N, Fukuda J, Hikichi H, Sakai N, Maehara S, Kawagoe-Takaki H, Hata M, Azuma T, Ito S, Kawamoto H, Ohta H: Pharmacological characterization of a new, orally active and potent allosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl- 3,6-dihydropyridine-1(2H)-carboxamide (FTIDC). J Pharmacol Exp Ther. 2007 Jun;321(3):1144-53. Epub 2007 Mar 14. [17360958 ]
  2. Chiocchetti A, Miglio G, Mesturini R, Varsaldi F, Mocellin M, Orilieri E, Dianzani C, Fantozzi R, Dianzani U, Lombardi G: Group I mGlu receptor stimulation inhibits activation-induced cell death of human T lymphocytes. Br J Pharmacol. 2006 Jul;148(6):760-8. Epub 2006 Jun 5. [16751798 ]
  3. San Gabriel AM, Maekawa T, Uneyama H, Yoshie S, Torii K: mGluR1 in the fundic glands of rat stomach. FEBS Lett. 2007 Mar 20;581(6):1119-23. Epub 2007 Feb 22. [17331504 ]
  4. Pellicciari R, Marinozzi M, Macchiarulo A, Fulco MC, Gafarova J, Serpi M, Giorgi G, Nielsen S, Thomsen C: Synthesis, molecular modeling studies, and preliminary pharmacological characterization of all possible 2-(2'-sulfonocyclopropyl)glycine stereoisomers as conformationally constrained L-homocysteic acid analogs. J Med Chem. 2007 Sep 20;50(19):4630-41. Epub 2007 Aug 29. [17725337 ]
  5. Filosa R, Carmela Fulco M, Marinozzi M, Giacche N, Macchiarulo A, Peduto A, Massa A, de Caprariis P, Thomsen C, Christoffersen CT, Pellicciari R: Design, synthesis and biological evaluation of novel bicyclo[1.1.1]pentane-based omega-acidic amino acids as glutamate receptors ligands. Bioorg Med Chem. 2009 Jan 1;17(1):242-50. doi: 10.1016/j.bmc.2008.11.015. Epub 2008 Nov 14. [19042134 ]
  6. Brauner-Osborne H, Egebjerg J, Nielsen EO, Madsen U, Krogsgaard-Larsen P: Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000 Jul 13;43(14):2609-45. [10893301 ]
Target Details
9. 4-aminobutyrate aminotransferase, mitochondrial
General Function:
Succinate-semialdehyde dehydrogenase binding
Specific Function:
Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine.
Gene Name:
ABAT
Uniprot ID:
P80404
Molecular Weight:
56438.405 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Imai H, Okuno T, Wu JY, Lee TJ: GABAergic innervation in cerebral blood vessels: an immunohistochemical demonstration of L-glutamic acid decarboxylase and GABA transaminase. J Cereb Blood Flow Metab. 1991 Jan;11(1):129-34. [1983997 ]
  4. Happola O, Paivarinta H, Soinila S, Wu JY, Panula P: Localization of L-glutamate decarboxylase and GABA transaminase immunoreactivity in the sympathetic ganglia of the rat. Neuroscience. 1987 Apr;21(1):271-81. [3299141 ]
  5. Far SR, Millimoria FR: Levels of glutamic acid decarboxylase (GAD), gamma amino butyric acid transaminase (GABA-T), glutamic acid dehydrogenase (GLDH) and proteins in cerebrospinal fluid of certain neurological disorders. Indian J Med Sci. 1996 Apr;50(4):99-102. [8979623 ]
Target Details
10. 5-oxoprolinase
General Function:
Atp binding
Specific Function:
Catalyzes the cleavage of 5-oxo-L-proline to form L-glutamate coupled to the hydrolysis of ATP to ADP and inorganic phosphate.
Gene Name:
OPLAH
Uniprot ID:
O14841
Molecular Weight:
137456.195 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Nishimura A, Itoh H, Oyama H, Murao S, Oda K: A simultaneous assay method for L-glutamate and L-pyroglutamate contents in soy sauce using a 5-oxoprolinase (without ATP hydrolyzing activity). Biosci Biotechnol Biochem. 2001 Feb;65(2):477-9. [11302195 ]
  4. Van der Werf P, Stephani RA, Orlowski M, Meister A: Inhibition of 5-oxoprolinase by 2-imidazolidone-4-carboxylic acid. Proc Natl Acad Sci U S A. 1973 Mar;70(3):759-61. [4514988 ]
  5. Seddon AP, Li LY, Meister A: Resolution of 5-oxo-L-prolinase into a 5-oxo-L-proline-dependent ATPase and a coupling protein. J Biol Chem. 1984 Jul 10;259(13):8091-4. [6145710 ]
Target Details
11. Alpha-aminoadipic semialdehyde synthase, mitochondrial
General Function:
Saccharopine dehydrogenase (nadp+, l-lysine-forming) activity
Specific Function:
Bifunctional enzyme that catalyzes the first two steps in lysine degradation. The N-terminal and the C-terminal contain lysine-ketoglutarate reductase and saccharopine dehydrogenase activity, respectively.
Gene Name:
AASS
Uniprot ID:
Q9UDR5
Molecular Weight:
102130.895 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Gaziola SA, Teixeira CM, Lugli J, Sodek L, Azevedo RA: The enzymology of lysine catabolism in rice seeds--isolation, characterization, and regulatory properties of a lysine 2-oxoglutarate reductase/saccharopine dehydrogenase bifunctional polypeptide. Eur J Biochem. 1997 Jul 1;247(1):364-71. [9249048 ]
  4. Goncalves-Butruille M, Szajner P, Torigoi E, Leite A, Arruda P: Purification and Characterization of the Bifunctional Enzyme Lysine-Ketoglutarate Reductase-Saccharopine Dehydrogenase from Maize. Plant Physiol. 1996 Mar;110(3):765-771. [12226216 ]
  5. Noda C, Ichihara A: Purification and properties of L-lysine-alpha-ketoglutarate reductase from rat liver mitochondria. Biochim Biophys Acta. 1978 Aug 7;525(2):307-13. [687635 ]
Target Details
12. Delta-1-pyrroline-5-carboxylate synthase
General Function:
Poly(a) rna binding
Specific Function:
Bifunctional enzyme that converts glutamate to glutamate 5-semialdehyde, an intermediate in the biosynthesis of proline, ornithine and arginine.
Gene Name:
ALDH18A1
Uniprot ID:
P54886
Molecular Weight:
87301.53 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Morita Y, Nakamori S, Takagi H: L-proline accumulation and freeze tolerance of Saccharomyces cerevisiae are caused by a mutation in the PRO1 gene encoding gamma-glutamyl kinase. Appl Environ Microbiol. 2003 Jan;69(1):212-9. [12513997 ]
  4. Krishna RV, Beilstein P, Leisinger T: Biosynthesis of proline in Pseudomonas aeruginosa. Properties of gamma-glutamyl phosphate reductase and 1-pyrroline-5-carboxylate reductase. Biochem J. 1979 Jul 1;181(1):223-30. [114173 ]
  5. Kamoun P, Aral B, Saudubray JM: [A new inherited metabolic disease: delta1-pyrroline 5-carboxylate synthetase deficiency]. Bull Acad Natl Med. 1998;182(1):131-7; discussion 138-9. [9622938 ]
Target Details
13. Excitatory amino acid transporter 2
General Function:
Sodium:dicarboxylate symporter activity
Specific Function:
Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium.
Gene Name:
SLC1A2
Uniprot ID:
P43004
Molecular Weight:
62103.665 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory62 uMNot AvailableBindingDB 17657
References
  1. King N, Lin H, McGivan JD, Suleiman MS: Expression and activity of the glutamate transporter EAAT2 in cardiac hypertrophy: implications for ischaemia reperfusion injury. Pflugers Arch. 2006 Sep;452(6):674-82. Epub 2006 May 23. [16718509 ]
  2. Nickell J, Salvatore MF, Pomerleau F, Apparsundaram S, Gerhardt GA: Reduced plasma membrane surface expression of GLAST mediates decreased glutamate regulation in the aged striatum. Neurobiol Aging. 2007 Nov;28(11):1737-48. Epub 2006 Sep 7. [16959378 ]
  3. Beart PM, O'Shea RD: Transporters for L-glutamate: an update on their molecular pharmacology and pathological involvement. Br J Pharmacol. 2007 Jan;150(1):5-17. Epub 2006 Nov 6. [17088867 ]
  4. Glowatzki E, Cheng N, Hiel H, Yi E, Tanaka K, Ellis-Davies GC, Rothstein JD, Bergles DE: The glutamate-aspartate transporter GLAST mediates glutamate uptake at inner hair cell afferent synapses in the mammalian cochlea. J Neurosci. 2006 Jul 19;26(29):7659-64. [16855093 ]
  5. Sagot E, Jensen AA, Pickering DS, Pu X, Umberti M, Stensbol TB, Nielsen B, Assaf Z, Aboab B, Bolte J, Gefflaut T, Bunch L: Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid: a novel selective inhibitor of human excitatory amino acid transporter subtype 2. J Med Chem. 2008 Jul 24;51(14):4085-92. doi: 10.1021/jm800091e. Epub 2008 Jun 25. [18578477 ]
Target Details
14. Excitatory amino acid transporter 3
General Function:
Sodium:dicarboxylate symporter activity
Specific Function:
Transports L-glutamate, L- and D-aspartate and L-cystein (PubMed:21123949). Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium. Negatively regulated by ARL6IP5 (By similarity).
Gene Name:
SLC1A1
Uniprot ID:
P43005
Molecular Weight:
57099.835 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.051 uMNot AvailableBindingDB 17657
References
  1. Menaker D, Bendahan A, Kanner BI: The substrate specificity of a neuronal glutamate transporter is determined by the nature of the coupling ion. J Neurochem. 2006 Oct;99(1):20-8. Epub 2006 Jul 11. [16831195 ]
  2. Yun JY, Park KS, Kim JH, Do SH, Zuo Z: Propofol reverses oxidative stress-attenuated glutamate transporter EAAT3 activity: evidence of protein kinase C involvement. Eur J Pharmacol. 2007 Jun 22;565(1-3):83-8. Epub 2007 Mar 3. [17382927 ]
  3. Tao Z, Grewer C: Cooperation of the conserved aspartate 439 and bound amino acid substrate is important for high-affinity Na+ binding to the glutamate transporter EAAC1. J Gen Physiol. 2007 Apr;129(4):331-44. [17389249 ]
  4. Nickell J, Salvatore MF, Pomerleau F, Apparsundaram S, Gerhardt GA: Reduced plasma membrane surface expression of GLAST mediates decreased glutamate regulation in the aged striatum. Neurobiol Aging. 2007 Nov;28(11):1737-48. Epub 2006 Sep 7. [16959378 ]
  5. Sagot E, Jensen AA, Pickering DS, Pu X, Umberti M, Stensbol TB, Nielsen B, Assaf Z, Aboab B, Bolte J, Gefflaut T, Bunch L: Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid: a novel selective inhibitor of human excitatory amino acid transporter subtype 2. J Med Chem. 2008 Jul 24;51(14):4085-92. doi: 10.1021/jm800091e. Epub 2008 Jun 25. [18578477 ]
Target Details
15. GMP synthase [glutamine-hydrolyzing]
General Function:
Pyrophosphatase activity
Specific Function:
Involved in the de novo synthesis of guanine nucleotides which are not only essential for DNA and RNA synthesis, but also provide GTP, which is involved in a number of cellular processes important for cell division.
Gene Name:
GMPS
Uniprot ID:
P49915
Molecular Weight:
76714.79 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Ravasio S, Dossena L, Martin-Figueroa E, Florencio FJ, Mattevi A, Morandi P, Curti B, Vanoni MA: Properties of the recombinant ferredoxin-dependent glutamate synthase of Synechocystis PCC6803. Comparison with the Azospirillum brasilense NADPH-dependent enzyme and its isolated alpha subunit. Biochemistry. 2002 Jun 25;41(25):8120-33. [12069605 ]
  4. Myers RS, Amaro RE, Luthey-Schulten ZA, Davisson VJ: Reaction coupling through interdomain contacts in imidazole glycerol phosphate synthase. Biochemistry. 2005 Sep 13;44(36):11974-85. [16142895 ]
  5. Boehlein SK, Richards NG, Schuster SM: Glutamine-dependent nitrogen transfer in Escherichia coli asparagine synthetase B. Searching for the catalytic triad. J Biol Chem. 1994 Mar 11;269(10):7450-7. [7907328 ]
Target Details
16. Glutamate decarboxylase 1
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the production of GABA.
Gene Name:
GAD1
Uniprot ID:
Q99259
Molecular Weight:
66896.065 Da
References
  1. Akama K, Takaiwa F: C-terminal extension of rice glutamate decarboxylase (OsGAD2) functions as an autoinhibitory domain and overexpression of a truncated mutant results in the accumulation of extremely high levels of GABA in plant cells. J Exp Bot. 2007;58(10):2699-707. Epub 2007 Jun 11. [17562689 ]
  2. Tueting P, Doueiri MS, Guidotti A, Davis JM, Costa E: Reelin down-regulation in mice and psychosis endophenotypes. Neurosci Biobehav Rev. 2006;30(8):1065-77. [16769115 ]
  3. Manto MU, Laute MA, Aguera M, Rogemond V, Pandolfo M, Honnorat J: Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases. Ann Neurol. 2007 Jun;61(6):544-51. [17600364 ]
  4. Wang FY, Zhu RM, Maemura K, Hirata I, Katsu K, Watanabe M: Expression of gamma-aminobutyric acid and glutamic acid decarboxylases in rat descending colon and their relation to epithelial differentiation. Chin J Dig Dis. 2006;7(2):103-8. [16643338 ]
  5. Tronci E, Simola N, Borsini F, Schintu N, Frau L, Carminati P, Morelli M: Characterization of the antiparkinsonian effects of the new adenosine A2A receptor antagonist ST1535: acute and subchronic studies in rats. Eur J Pharmacol. 2007 Jul 2;566(1-3):94-102. Epub 2007 Mar 24. [17445798 ]
Target Details
17. Glutamate decarboxylase 2
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the production of GABA.
Gene Name:
GAD2
Uniprot ID:
Q05329
Molecular Weight:
65410.77 Da
References
  1. Wei J, Lin CH, Wu H, Jin Y, Lee YH, Wu JY: Activity-dependent cleavage of brain glutamic acid decarboxylase 65 by calpain. J Neurochem. 2006 Sep;98(5):1688-95. Epub 2006 Jul 31. [16879709 ]
  2. Manto MU, Laute MA, Aguera M, Rogemond V, Pandolfo M, Honnorat J: Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases. Ann Neurol. 2007 Jun;61(6):544-51. [17600364 ]
  3. Pop SM, Wong CP, He Q, Wang Y, Wallet MA, Goudy KS, Tisch R: The type and frequency of immunoregulatory CD4+ T-cells govern the efficacy of antigen-specific immunotherapy in nonobese diabetic mice. Diabetes. 2007 May;56(5):1395-402. Epub 2007 Feb 22. [17317763 ]
  4. Wang FY, Zhu RM, Maemura K, Hirata I, Katsu K, Watanabe M: Expression of gamma-aminobutyric acid and glutamic acid decarboxylases in rat descending colon and their relation to epithelial differentiation. Chin J Dig Dis. 2006;7(2):103-8. [16643338 ]
  5. Castelli MP, Piras AP, Melis T, Succu S, Sanna F, Melis MR, Collu S, Ennas MG, Diaz G, Mackie K, Argiolas A: Cannabinoid CB1 receptors in the paraventricular nucleus and central control of penile erection: immunocytochemistry, autoradiography and behavioral studies. Neuroscience. 2007 Jun 15;147(1):197-206. Epub 2007 May 15. [17507169 ]
Target Details
18. Glutamate receptor ionotropic, NMDA 2A
General Function:
Zinc ion binding
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits.
Gene Name:
GRIN2A
Uniprot ID:
Q12879
Molecular Weight:
165281.215 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Rutter AR, Freeman FM, Stephenson FA: Further characterization of the molecular interaction between PSD-95 and NMDA receptors: the effect of the NR1 splice variant and evidence for modulation of channel gating. J Neurochem. 2002 Jun;81(6):1298-307. [12068077 ]
  4. Rutter AR, Stephenson FA: Coexpression of postsynaptic density-95 protein with NMDA receptors results in enhanced receptor expression together with a decreased sensitivity to L-glutamate. J Neurochem. 2000 Dec;75(6):2501-10. [11080203 ]
  5. Bresink I, Benke TA, Collett VJ, Seal AJ, Parsons CG, Henley JM, Collingridge GL: Effects of memantine on recombinant rat NMDA receptors expressed in HEK 293 cells. Br J Pharmacol. 1996 Sep;119(2):195-204. [8886398 ]
Target Details
19. Glutamate receptor ionotropic, NMDA 2C
General Function:
Nmda glutamate receptor activity
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name:
GRIN2C
Uniprot ID:
Q14957
Molecular Weight:
134207.77 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Kuner T, Schoepfer R, Korpi ER: Ethanol inhibits glutamate-induced currents in heteromeric NMDA receptor subtypes. Neuroreport. 1993 Dec 13;5(3):297-300. [7905294 ]
  4. Olmos G, DeGregorio-Rocasolano N, Paz Regalado M, Gasull T, Assumpcio Boronat M, Trullas R, Villarroel A, Lerma J, Garcia-Sevilla JA: Protection by imidazol(ine) drugs and agmatine of glutamate-induced neurotoxicity in cultured cerebellar granule cells through blockade of NMDA receptor. Br J Pharmacol. 1999 Jul;127(6):1317-26. [10455281 ]
  5. Sundstrom E, Whittemore S, Mo LL, Seiger A: Analysis of NMDA receptors in the human spinal cord. Exp Neurol. 1997 Dec;148(2):407-13. [9417820 ]
Target Details
20. Glutamate receptor ionotropic, NMDA 2D
General Function:
Nmda glutamate receptor activity
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name:
GRIN2D
Uniprot ID:
O15399
Molecular Weight:
143750.685 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Pliss L, Jezova D, Mares V, Balcar VJ, St'astny F: N-Acetyl-L-aspartyl-L-glutamate changes functional and structural properties of rat blood-brain barrier. Neurosci Lett. 2002 Jan 11;317(2):85-8. [11755246 ]
  4. Bresink I, Benke TA, Collett VJ, Seal AJ, Parsons CG, Henley JM, Collingridge GL: Effects of memantine on recombinant rat NMDA receptors expressed in HEK 293 cells. Br J Pharmacol. 1996 Sep;119(2):195-204. [8886398 ]
  5. Sundstrom E, Whittemore S, Mo LL, Seiger A: Analysis of NMDA receptors in the human spinal cord. Exp Neurol. 1997 Dec;148(2):407-13. [9417820 ]
Target Details
21. Glutaminase kidney isoform, mitochondrial
General Function:
Glutaminase activity
Specific Function:
Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate in the brain. Isoform 2 lacks catalytic activity.
Gene Name:
GLS
Uniprot ID:
O94925
Molecular Weight:
73460.56 Da
References
  1. Karmaker S, Saha TK, Yoshikawa Y, Yasui H, Sakurai H: A novel drug delivery system for type 1 diabetes: insulin-mimetic vanadyl-poly(gamma-glutamic acid) complex. J Inorg Biochem. 2006 Sep;100(9):1535-46. Epub 2006 May 24. [16824605 ]
  2. Shi F, Xu Z, Cen P: Efficient production of poly-gamma-glutamic acid by Bacillus subtilis ZJU-7. Appl Biochem Biotechnol. 2006 Jun;133(3):271-82. [16720907 ]
  3. Yang XX, Hu ZP, Xu AL, Duan W, Zhu YZ, Huang M, Sheu FS, Zhang Q, Bian JS, Chan E, Li X, Wang JC, Zhou SF: A mechanistic study on reduced toxicity of irinotecan by coadministered thalidomide, a tumor necrosis factor-alpha inhibitor. J Pharmacol Exp Ther. 2006 Oct;319(1):82-104. Epub 2006 Jun 30. [16815871 ]
  4. Ashiuchi M, Shimanouchi K, Horiuchi T, Kamei T, Misono H: Genetically engineered poly-gamma-glutamate producer from Bacillus subtilis ISW1214. Biosci Biotechnol Biochem. 2006 Jul;70(7):1794-7. [16861819 ]
  5. Ashiuchi M, Nakamura H, Yamamoto M, Misono H: Novel poly-gamma-glutamate-processing enzyme catalyzing gamma-glutamyl DD-amidohydrolysis. J Biosci Bioeng. 2006 Jul;102(1):60-5. [16952838 ]
Target Details
22. Glutamyl aminopeptidase
General Function:
Zinc ion binding
Specific Function:
Appears to have a role in the catabolic pathway of the renin-angiotensin system. Probably plays a role in regulating growth and differentiation of early B-lineage cells.
Gene Name:
ENPEP
Uniprot ID:
Q07075
Molecular Weight:
109243.58 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Tobe H, Kojima F, Aoyagi T, Umezawa H: Purification by affinity chromatography using amastatin and properties of aminopeptidase A from pig kidney. Biochim Biophys Acta. 1980 Jun 13;613(2):459-68. [7448199 ]
  4. Acarturk F, Parlatan ZI, Saracoglu OF: Comparison of vaginal aminopeptidase enzymatic activities in various animals and in humans. J Pharm Pharmacol. 2001 Nov;53(11):1499-504. [11732752 ]
  5. Sasaki M, Bosman BW, Tan PS: Comparison of proteolytic activities in various lactobacilli. J Dairy Res. 1995 Nov;62(4):601-10. [8568030 ]
Target Details
23. Metabotropic glutamate receptor 4
General Function:
Group iii metabotropic glutamate receptor activity
Specific Function:
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity.
Gene Name:
GRM4
Uniprot ID:
Q14833
Molecular Weight:
101866.835 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1.4 uMNot AvailableBindingDB 17657
Inhibitory2.4 uMNot AvailableBindingDB 17657
Inhibitory3 uMNot AvailableBindingDB 17657
Inhibitory17 uMNot AvailableBindingDB 17657
References
  1. Suzuki G, Kimura T, Satow A, Kaneko N, Fukuda J, Hikichi H, Sakai N, Maehara S, Kawagoe-Takaki H, Hata M, Azuma T, Ito S, Kawamoto H, Ohta H: Pharmacological characterization of a new, orally active and potent allosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl- 3,6-dihydropyridine-1(2H)-carboxamide (FTIDC). J Pharmacol Exp Ther. 2007 Jun;321(3):1144-53. Epub 2007 Mar 14. [17360958 ]
  2. Filosa R, Carmela Fulco M, Marinozzi M, Giacche N, Macchiarulo A, Peduto A, Massa A, de Caprariis P, Thomsen C, Christoffersen CT, Pellicciari R: Design, synthesis and biological evaluation of novel bicyclo[1.1.1]pentane-based omega-acidic amino acids as glutamate receptors ligands. Bioorg Med Chem. 2009 Jan 1;17(1):242-50. doi: 10.1016/j.bmc.2008.11.015. Epub 2008 Nov 14. [19042134 ]
  3. Pellicciari R, Marinozzi M, Macchiarulo A, Fulco MC, Gafarova J, Serpi M, Giorgi G, Nielsen S, Thomsen C: Synthesis, molecular modeling studies, and preliminary pharmacological characterization of all possible 2-(2'-sulfonocyclopropyl)glycine stereoisomers as conformationally constrained L-homocysteic acid analogs. J Med Chem. 2007 Sep 20;50(19):4630-41. Epub 2007 Aug 29. [17725337 ]
  4. Conn PJ, Pin JP: Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol. 1997;37:205-37. [9131252 ]
  5. Brauner-Osborne H, Egebjerg J, Nielsen EO, Madsen U, Krogsgaard-Larsen P: Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000 Jul 13;43(14):2609-45. [10893301 ]
Target Details
24. Aspartate aminotransferase, mitochondrial
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). Plays a key role in amino acid metabolism. Important for metabolite exchange between mitochondria and cytosol. Facilitates cellular uptake of long-chain free fatty acids.
Gene Name:
GOT2
Uniprot ID:
P00505
Molecular Weight:
47517.285 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Recasens M, Mandel P: Similarities between cysteinesulphinate transaminase and aspartate aminotransferase. Ciba Found Symp. 1979;(72):259-70. [261660 ]
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
Target Details
25. Bifunctional glutamate/proline--tRNA ligase
General Function:
Rna stem-loop binding
Specific Function:
Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.
Gene Name:
EPRS
Uniprot ID:
P07814
Molecular Weight:
170589.705 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Cerini C, Semeriva M, Gratecos D: Evolution of the aminoacyl-tRNA synthetase family and the organization of the Drosophila glutamyl-prolyl-tRNA synthetase gene. Intron/exon structure of the gene, control of expression of the two mRNAs, selective advantage of the multienzyme complex. Eur J Biochem. 1997 Feb 15;244(1):176-85. [9063462 ]
  4. Ting SM, Dignam JD: Post-transcriptional regulation of glutamyl-prolyl-tRNA synthetase in rat salivary gland. J Biol Chem. 1994 Mar 25;269(12):8993-8. [8132637 ]
Target Details
26. Excitatory amino acid transporter 1
General Function:
Sodium:dicarboxylate symporter activity
Specific Function:
Transports L-glutamate and also L- and D-aspartate. Essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. Acts as a symport by cotransporting sodium.
Gene Name:
SLC1A3
Uniprot ID:
P43003
Molecular Weight:
59571.855 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory35 uMNot AvailableBindingDB 17657
References
  1. Glowatzki E, Cheng N, Hiel H, Yi E, Tanaka K, Ellis-Davies GC, Rothstein JD, Bergles DE: The glutamate-aspartate transporter GLAST mediates glutamate uptake at inner hair cell afferent synapses in the mammalian cochlea. J Neurosci. 2006 Jul 19;26(29):7659-64. [16855093 ]
  2. Beart PM, O'Shea RD: Transporters for L-glutamate: an update on their molecular pharmacology and pathological involvement. Br J Pharmacol. 2007 Jan;150(1):5-17. Epub 2006 Nov 6. [17088867 ]
  3. Nickell J, Salvatore MF, Pomerleau F, Apparsundaram S, Gerhardt GA: Reduced plasma membrane surface expression of GLAST mediates decreased glutamate regulation in the aged striatum. Neurobiol Aging. 2007 Nov;28(11):1737-48. Epub 2006 Sep 7. [16959378 ]
  4. Sagot E, Jensen AA, Pickering DS, Pu X, Umberti M, Stensbol TB, Nielsen B, Assaf Z, Aboab B, Bolte J, Gefflaut T, Bunch L: Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid: a novel selective inhibitor of human excitatory amino acid transporter subtype 2. J Med Chem. 2008 Jul 24;51(14):4085-92. doi: 10.1021/jm800091e. Epub 2008 Jun 25. [18578477 ]
Target Details
27. Excitatory amino acid transporter 4
General Function:
Sodium:dicarboxylate symporter activity
Specific Function:
Transports L-glutamate and also L- and D-aspartate. Seems to act as a symport by cotransporting sodium.
Gene Name:
SLC1A6
Uniprot ID:
P48664
Molecular Weight:
61564.875 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Gegelashvili G, Schousboe A: High affinity glutamate transporters: regulation of expression and activity. Mol Pharmacol. 1997 Jul;52(1):6-15. [9224806 ]
  4. Lin CL, Tzingounis AV, Jin L, Furuta A, Kavanaugh MP, Rothstein JD: Molecular cloning and expression of the rat EAAT4 glutamate transporter subtype. Brain Res Mol Brain Res. 1998 Dec 10;63(1):174-9. [9838098 ]
Target Details
28. Excitatory amino acid transporter 5
General Function:
Sodium:dicarboxylate symporter activity
Specific Function:
Transports L-glutamate; the L-glutamate uptake is sodium- and voltage-dependent and chloride-independent. Its associated chloride conductance may participate in visual processing.
Gene Name:
SLC1A7
Uniprot ID:
O00341
Molecular Weight:
60657.825 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Takarada T, Hinoi E, Balcar VJ, Taniura H, Yoneda Y: Possible expression of functional glutamate transporters in the rat testis. J Endocrinol. 2004 May;181(2):233-44. [15128272 ]
  4. Arriza JL, Eliasof S, Kavanaugh MP, Amara SG: Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4155-60. [9108121 ]
Target Details
29. Glutamine synthetase
General Function:
Manganese ion binding
Specific Function:
This enzyme has 2 functions: it catalyzes the production of glutamine and 4-aminobutanoate (gamma-aminobutyric acid, GABA), the latter in a pyridoxal phosphate-independent manner (By similarity). Essential for proliferation of fetal skin fibroblasts.
Gene Name:
GLUL
Uniprot ID:
P15104
Molecular Weight:
42064.15 Da
References
  1. Re DB, Nafia I, Melon C, Shimamoto K, Kerkerian-Le Goff L, Had-Aissouni L: Glutamate leakage from a compartmentalized intracellular metabolic pool and activation of the lipoxygenase pathway mediate oxidative astrocyte death by reversed glutamate transport. Glia. 2006 Jul;54(1):47-57. [16673373 ]
  2. Singh U, Sarkar D: Development of a simple high-throughput screening protocol based on biosynthetic activity of Mycobacterium tuberculosis glutamine synthetase for the identification of novel Inhibitors. J Biomol Screen. 2006 Dec;11(8):1035-42. Epub 2006 Sep 14. [16973920 ]
  3. Yamamoto S, Wakayama M, Tachiki T: Characterization of theanine-forming enzyme from Methylovorus mays no. 9 in respect to utilization of theanine production. Biosci Biotechnol Biochem. 2007 Feb;71(2):545-52. Epub 2007 Feb 7. [17284842 ]
  4. Scaraffia PY, Zhang Q, Wysocki VH, Isoe J, Wells MA: Analysis of whole body ammonia metabolism in Aedes aegypti using [15N]-labeled compounds and mass spectrometry. Insect Biochem Mol Biol. 2006 Aug;36(8):614-22. Epub 2006 May 19. [16876704 ]
Target Details
30. Metabotropic glutamate receptor 2
General Function:
Group ii metabotropic glutamate receptor activity
Specific Function:
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization.
Gene Name:
GRM2
Uniprot ID:
Q14416
Molecular Weight:
95566.715 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory4 uMNot AvailableBindingDB 17657
Inhibitory6.4 uMNot AvailableBindingDB 17657
Inhibitory11 uMNot AvailableBindingDB 17657
Inhibitory12 uMNot AvailableBindingDB 17657
References
  1. Conn PJ, Pin JP: Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol. 1997;37:205-37. [9131252 ]
  2. Filosa R, Carmela Fulco M, Marinozzi M, Giacche N, Macchiarulo A, Peduto A, Massa A, de Caprariis P, Thomsen C, Christoffersen CT, Pellicciari R: Design, synthesis and biological evaluation of novel bicyclo[1.1.1]pentane-based omega-acidic amino acids as glutamate receptors ligands. Bioorg Med Chem. 2009 Jan 1;17(1):242-50. doi: 10.1016/j.bmc.2008.11.015. Epub 2008 Nov 14. [19042134 ]
  3. Pellicciari R, Marinozzi M, Macchiarulo A, Fulco MC, Gafarova J, Serpi M, Giorgi G, Nielsen S, Thomsen C: Synthesis, molecular modeling studies, and preliminary pharmacological characterization of all possible 2-(2'-sulfonocyclopropyl)glycine stereoisomers as conformationally constrained L-homocysteic acid analogs. J Med Chem. 2007 Sep 20;50(19):4630-41. Epub 2007 Aug 29. [17725337 ]
  4. Brauner-Osborne H, Egebjerg J, Nielsen EO, Madsen U, Krogsgaard-Larsen P: Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000 Jul 13;43(14):2609-45. [10893301 ]
Target Details
31. Metabotropic glutamate receptor 8
General Function:
Group iii metabotropic glutamate receptor activity
Specific Function:
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.
Gene Name:
GRM8
Uniprot ID:
O00222
Molecular Weight:
101739.575 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory9.5 uMNot AvailableBindingDB 17657
IC500.0057 uMNot AvailableBindingDB 17657
References
  1. Suzuki G, Kimura T, Satow A, Kaneko N, Fukuda J, Hikichi H, Sakai N, Maehara S, Kawagoe-Takaki H, Hata M, Azuma T, Ito S, Kawamoto H, Ohta H: Pharmacological characterization of a new, orally active and potent allosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl- 3,6-dihydropyridine-1(2H)-carboxamide (FTIDC). J Pharmacol Exp Ther. 2007 Jun;321(3):1144-53. Epub 2007 Mar 14. [17360958 ]
  2. Morimoto R, Uehara S, Yatsushiro S, Juge N, Hua Z, Senoh S, Echigo N, Hayashi M, Mizoguchi T, Ninomiya T, Udagawa N, Omote H, Yamamoto A, Edwards RH, Moriyama Y: Secretion of L-glutamate from osteoclasts through transcytosis. EMBO J. 2006 Sep 20;25(18):4175-86. Epub 2006 Sep 7. [16957773 ]
  3. Wheeler WJ, Clodfelter DK, Collado I, Kulanthaivel P, Pedregal C, Stoddard EA, Wright RA, Schoepp DD: (2S,1'S,2'R,3'R)-2(2'-Carboxy-3'-hydroxymethylcyclopropyl)glycine-[3H], a potent and selective radioligand for labeling group 2 and 3 metabotropic glutamate receptors. Bioorg Med Chem Lett. 2005 Jan 17;15(2):349-51. [15603952 ]
  4. Brauner-Osborne H, Egebjerg J, Nielsen EO, Madsen U, Krogsgaard-Larsen P: Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000 Jul 13;43(14):2609-45. [10893301 ]
Target Details
32. Phosphoserine aminotransferase
General Function:
O-phospho-l-serine:2-oxoglutarate aminotransferase activity
Specific Function:
Catalyzes the reversible conversion of 3-phosphohydroxypyruvate to phosphoserine and of 3-hydroxy-2-oxo-4-phosphonooxybutanoate to phosphohydroxythreonine.
Gene Name:
PSAT1
Uniprot ID:
Q9Y617
Molecular Weight:
40422.355 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Hester G, Stark W, Moser M, Kallen J, Markovic-Housley Z, Jansonius JN: Crystal structure of phosphoserine aminotransferase from Escherichia coli at 2.3 A resolution: comparison of the unligated enzyme and a complex with alpha-methyl-l-glutamate. J Mol Biol. 1999 Feb 26;286(3):829-50. [10024454 ]
  4. Katsura Y, Shirouzu M, Yamaguchi H, Ishitani R, Nureki O, Kuramitsu S, Hayashi H, Yokoyama S: Crystal structure of a putative aspartate aminotransferase belonging to subgroup IV. Proteins. 2004 May 15;55(3):487-92. [15103612 ]
Target Details
33. Aspartyl aminopeptidase
General Function:
Zinc ion binding
Specific Function:
Aminopeptidase with specificity towards an acidic amino acid at the N-terminus. Likely to play an important role in intracellular protein and peptide metabolism.
Gene Name:
DNPEP
Uniprot ID:
Q9ULA0
Molecular Weight:
52427.87 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Watanabe J, Tanaka H, Akagawa T, Mogi Y, Yamazaki T: Characterization of Aspergillus oryzae aspartyl aminopeptidase expressed in Escherichia coli. Biosci Biotechnol Biochem. 2007 Oct;71(10):2557-60. Epub 2007 Oct 7. [17928682 ]
Target Details
34. Carboxypeptidase Q
General Function:
Protein homodimerization activity
Specific Function:
Carboxypeptidase that may play an important role in the hydrolysis of circulating peptides. Catalyzes the hydrolysis of dipeptides with unsubstituted terminals into amino acids. May play a role in the liberation of thyroxine hormone from its thyroglobulin (Tg) precursor.
Gene Name:
CPQ
Uniprot ID:
Q9Y646
Molecular Weight:
51887.185 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
Target Details
35. Formimidoyltransferase-cyclodeaminase
General Function:
Microtubule binding
Specific Function:
Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool.Binds and promotes bundling of vimentin filaments originating from the Golgi.
Gene Name:
FTCD
Uniprot ID:
O95954
Molecular Weight:
58925.93 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Gao YS, Alvarez C, Nelson DS, Sztul E: Molecular cloning, characterization, and dynamics of rat formiminotransferase cyclodeaminase, a Golgi-associated 58-kDa protein. J Biol Chem. 1998 Dec 11;273(50):33825-34. [9837973 ]
Target Details
36. Glutamate dehydrogenase 1, mitochondrial
General Function:
Nad+ binding
Specific Function:
Mitochondrial glutamate dehydrogenase that converts L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle. May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity).
Gene Name:
GLUD1
Uniprot ID:
P00367
Molecular Weight:
61397.315 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Anagnou NP, Seuanez H, Modi W, O'Brien SJ, Papamatheakis J, Moschonas NK: Chromosomal mapping of two members of the human glutamate dehydrogenase (GLUD) gene family to chromosomes 10q22.3-q23 and Xq22-q23. Hum Hered. 1993 Nov-Dec;43(6):351-6. [8288265 ]
Target Details
37. Glutamate receptor 3
General Function:
Extracellular-glutamate-gated ion channel activity
Specific Function:
Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.
Gene Name:
GRIA3
Uniprot ID:
P42263
Molecular Weight:
101155.975 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Henley JM, Jenkins R, Hunt SP: Localisation of glutamate receptor binding sites and mRNAs to the dorsal horn of the rat spinal cord. Neuropharmacology. 1993 Jan;32(1):37-41. [7679210 ]
Target Details
38. Glutamate receptor ionotropic, kainate 4
General Function:
Kainate selective glutamate receptor activity
Specific Function:
Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists.
Gene Name:
GRIK4
Uniprot ID:
Q16099
Molecular Weight:
107244.485 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Korczak B, Nutt SL, Fletcher EJ, Hoo KH, Elliott CE, Rampersad V, McWhinnie EA, Kamboj RK: cDNA cloning and functional properties of human glutamate receptor EAA3 (GluR5) in homomeric and heteromeric configuration. Receptors Channels. 1995;3(1):41-9. [8589992 ]
Target Details
39. Glutaminase liver isoform, mitochondrial
General Function:
Glutaminase activity
Specific Function:
Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation.
Gene Name:
GLS2
Uniprot ID:
Q9UI32
Molecular Weight:
66322.225 Da
References
  1. Dossena L, Curti B, Vanoni MA: Activation and coupling of the glutaminase and synthase reaction of glutamate synthase is mediated by E1013 of the ferredoxin-dependent enzyme, belonging to loop 4 of the synthase domain. Biochemistry. 2007 Apr 17;46(15):4473-85. Epub 2007 Mar 21. [17373776 ]
  2. Kita K, Suzuki T, Ochi T: Down-regulation of glutaminase C in human hepatocarcinoma cell by diphenylarsinic acid, a degradation product of chemical warfare agents. Toxicol Appl Pharmacol. 2007 May 1;220(3):262-70. Epub 2007 Jan 24. [17321558 ]
  3. Yoshimune K, Shirakihara Y, Shiratori A, Wakayama M, Chantawannakul P, Moriguchi M: Crystal structure of a major fragment of the salt-tolerant glutaminase from Micrococcus luteus K-3. Biochem Biophys Res Commun. 2006 Aug 11;346(4):1118-24. Epub 2006 Jun 6. [16793004 ]
Target Details
40. Kynurenine/alpha-aminoadipate aminotransferase, mitochondrial
General Function:
Pyridoxal phosphate binding
Specific Function:
Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro).
Gene Name:
AADAT
Uniprot ID:
Q8N5Z0
Molecular Weight:
47351.17 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Kocki T, Luchowski P, Luchowska E, Wielosz M, Turski WA, Urbanska EM: L-cysteine sulphinate, endogenous sulphur-containing amino acid, inhibits rat brain kynurenic acid production via selective interference with kynurenine aminotransferase II. Neurosci Lett. 2003 Jul 31;346(1-2):97-100. [12850557 ]
Target Details
41. Phosphoribosylformylglycinamidine synthase
General Function:
Phosphoribosylformylglycinamidine synthase activity
Specific Function:
Phosphoribosylformylglycinamidine synthase involved in the purines biosynthetic pathway. Catalyzes the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) and glutamine to yield formylglycinamidine ribonucleotide (FGAM) and glutamate (By similarity).
Gene Name:
PFAS
Uniprot ID:
O15067
Molecular Weight:
144733.165 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Jayaram HN, Lui MS, Plowman J, Pillwein K, Reardon MA, Elliott WL, Weber G: Oncolytic activity and mechanism of action of a novel L-cysteine derivative, L-cysteine, ethyl ester, S-(N-methylcarbamate) monohydrochloride. Cancer Chemother Pharmacol. 1990;26(2):88-92. [2347042 ]
Target Details
42. Alanine aminotransferase 2
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate.
Gene Name:
GPT2
Uniprot ID:
Q8TD30
Molecular Weight:
57903.11 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
43. Asparagine synthetase [glutamine-hydrolyzing]
General Function:
Protein homodimerization activity
Specific Function:
Not Available
Gene Name:
ASNS
Uniprot ID:
P08243
Molecular Weight:
64369.39 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
44. Aspartate aminotransferase
General Function:
Pyridoxal phosphate binding
Specific Function:
Not Available
Gene Name:
GIG18
Uniprot ID:
Q2TU84
Molecular Weight:
46319.2 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
45. Branched-chain-amino-acid aminotransferase, mitochondrial
General Function:
L-valine transaminase activity
Specific Function:
Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine. May also function as a transporter of branched chain alpha-keto acids.
Gene Name:
BCAT2
Uniprot ID:
O15382
Molecular Weight:
44287.445 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
46. Folylpolyglutamate synthase, mitochondrial
General Function:
Tetrahydrofolylpolyglutamate synthase activity
Specific Function:
Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis. Unsubstituted reduced folates are the preferred substrates. Metabolizes methotrexate (MTX) to polyglutamates.
Gene Name:
FPGS
Uniprot ID:
Q05932
Molecular Weight:
64608.53 Da
References
  1. DeMartino JK, Hwang I, Xu L, Wilson IA, Boger DL: Discovery of a potent, nonpolyglutamatable inhibitor of glycinamide ribonucleotide transformylase. J Med Chem. 2006 May 18;49(10):2998-3002. [16686541 ]
  2. Gangjee A, Yang J, McGuire JJ, Kisliuk RL: Synthesis and evaluation of a classical 2,4-diamino-5-substituted-furo[2,3-d]pyrimidine and a 2-amino-4-oxo-6-substituted-pyrrolo[2,3-d]pyrimidine as antifolates. Bioorg Med Chem. 2006 Dec 15;14(24):8590-8. Epub 2006 Sep 20. [16990006 ]
Target Details
47. Glutamate dehydrogenase 2, mitochondrial
General Function:
Leucine binding
Specific Function:
Important for recycling the chief excitatory neurotransmitter, glutamate, during neurotransmission.
Gene Name:
GLUD2
Uniprot ID:
P49448
Molecular Weight:
61433.465 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
48. Glutamate receptor ionotropic, NMDA 2B
General Function:
Zinc ion binding
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity).
Gene Name:
GRIN2B
Uniprot ID:
Q13224
Molecular Weight:
166365.885 Da
References
  1. Verkhratsky A, Kirchhoff F: NMDA Receptors in glia. Neuroscientist. 2007 Feb;13(1):28-37. [17229973 ]
  2. Miglio G, Dianzani C, Fallarini S, Fantozzi R, Lombardi G: Stimulation of N-methyl-D-aspartate receptors modulates Jurkat T cell growth and adhesion to fibronectin. Biochem Biophys Res Commun. 2007 Sep 21;361(2):404-9. Epub 2007 Jul 20. [17662248 ]
Target Details
49. Glutamate receptor ionotropic, NMDA 3A
General Function:
Protein phosphatase 2a binding
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism (By similarity).
Gene Name:
GRIN3A
Uniprot ID:
Q8TCU5
Molecular Weight:
125464.07 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
50. Glutamate receptor ionotropic, NMDA 3B
General Function:
Nmda glutamate receptor activity
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name:
GRIN3B
Uniprot ID:
O60391
Molecular Weight:
112990.98 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
51. Glutamate receptor ionotropic, delta-1
General Function:
Ionotropic glutamate receptor activity
Specific Function:
Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists.
Gene Name:
GRID1
Uniprot ID:
Q9ULK0
Molecular Weight:
112129.96 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
52. Glutamate receptor ionotropic, delta-2
General Function:
Scaffold protein binding
Specific Function:
Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists.
Gene Name:
GRID2
Uniprot ID:
O43424
Molecular Weight:
113355.16 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
53. Glutamate receptor ionotropic, kainate 2
General Function:
Kainate selective glutamate receptor activity
Specific Function:
Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus. Modulates cell surface expression of NETO2 (By similarity).
Gene Name:
GRIK2
Uniprot ID:
Q13002
Molecular Weight:
102582.475 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1.106 uMNot AvailableBindingDB 17657
References
  1. Wong AY, MacLean DM, Bowie D: Na+/Cl- dipole couples agonist binding to kainate receptor activation. J Neurosci. 2007 Jun 20;27(25):6800-9. [17581967 ]
  2. Baker SR, Bleakman D, Ezquerra J, Ballyk BA, Deverill M, Ho K, Kamboj RK, Collado I, Dominguez C, Escribano A, Mateo AI, Pedregal C, Rubio A: 4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists. Bioorg Med Chem Lett. 2000 Aug 21;10(16):1807-10. [10969973 ]
Target Details
54. Glutamate--cysteine ligase catalytic subunit
General Function:
Magnesium ion binding
Specific Function:
Not Available
Gene Name:
GCLC
Uniprot ID:
P48506
Molecular Weight:
72765.14 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
55. Glutamine-dependent NAD(+) synthetase
General Function:
Nad+ synthase (glutamine-hydrolyzing) activity
Specific Function:
Not Available
Gene Name:
NADSYN1
Uniprot ID:
Q6IA69
Molecular Weight:
79283.945 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
56. Glutamyl-tRNA(Gln) amidotransferase subunit B, mitochondrial
General Function:
Translation factor activity, rna binding
Specific Function:
Allows the formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria. The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln).
Gene Name:
GATB
Uniprot ID:
O75879
Molecular Weight:
61863.57 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
57. Kynurenine--oxoglutarate transaminase 3
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). May catalyze the beta-elimination of S-conjugates and Se-conjugates of L-(seleno)cysteine, resulting in the cleavage of the C-S or C-Se bond (By similarity). Has transaminase activity towards L-kynurenine, tryptophan, phenylalanine, serine, cysteine, methionine, histidine, glutamine and asparagine with glyoxylate as an amino group acceptor (in vitro). Has lower activity with 2-oxoglutarate as amino group acceptor (in vitro) (By similarity).
Gene Name:
CCBL2
Uniprot ID:
Q6YP21
Molecular Weight:
51399.855 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
58. Lengsin
General Function:
Glutamate-ammonia ligase activity
Specific Function:
May act as a component of the cytoskeleton or as a chaperone for the reorganization of intermediate filament proteins during terminal differentiation in the lens. Does not seem to have enzymatic activity (By similarity).
Gene Name:
LGSN
Uniprot ID:
Q5TDP6
Molecular Weight:
57277.46 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
59. Metabotropic glutamate receptor 6
General Function:
Protein homodimerization activity
Specific Function:
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity (By similarity). Signaling stimulates TRPM1 channel activity and Ca(2+) uptake. Required for normal vision.
Gene Name:
GRM6
Uniprot ID:
O15303
Molecular Weight:
95466.77 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory38 uMNot AvailableBindingDB 17657
Inhibitory>10 uMNot AvailableBindingDB 17657
References
  1. Brauner-Osborne H, Egebjerg J, Nielsen EO, Madsen U, Krogsgaard-Larsen P: Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000 Jul 13;43(14):2609-45. [10893301 ]
  2. Conn PJ, Pin JP: Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol. 1997;37:205-37. [9131252 ]
Target Details
60. Metabotropic glutamate receptor 7
General Function:
Voltage-gated calcium channel activity
Specific Function:
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.
Gene Name:
GRM7
Uniprot ID:
Q14831
Molecular Weight:
102250.06 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory5400 uMNot AvailableBindingDB 17657
References
  1. Suzuki G, Kimura T, Satow A, Kaneko N, Fukuda J, Hikichi H, Sakai N, Maehara S, Kawagoe-Takaki H, Hata M, Azuma T, Ito S, Kawamoto H, Ohta H: Pharmacological characterization of a new, orally active and potent allosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl- 3,6-dihydropyridine-1(2H)-carboxamide (FTIDC). J Pharmacol Exp Ther. 2007 Jun;321(3):1144-53. Epub 2007 Mar 14. [17360958 ]
  2. Brauner-Osborne H, Egebjerg J, Nielsen EO, Madsen U, Krogsgaard-Larsen P: Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000 Jul 13;43(14):2609-45. [10893301 ]
Target Details
61. Mitochondrial glutamate carrier 1
General Function:
Symporter activity
Specific Function:
Involved in the transport of glutamate across the inner mitochondrial membrane. Glutamate is cotransported with H(+).
Gene Name:
SLC25A22
Uniprot ID:
Q9H936
Molecular Weight:
34469.85 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
62. Mitochondrial glutamate carrier 2
General Function:
Symporter activity
Specific Function:
Involved in the transport of glutamate across the inner mitochondrial membrane. Glutamate is cotransported with H(+).
Gene Name:
SLC25A18
Uniprot ID:
Q9H1K4
Molecular Weight:
33848.44 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
63. Vitamin K-dependent gamma-carboxylase
General Function:
Gamma-glutamyl carboxylase activity
Specific Function:
Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vitamin K to vitamin K epoxide.
Gene Name:
GGCX
Uniprot ID:
P38435
Molecular Weight:
87560.065 Da
References
  1. Zhu A, Sun H, Raymond RM Jr, Furie BC, Furie B, Bronstein M, Kaufman RJ, Westrick R, Ginsburg D: Fatal hemorrhage in mice lacking gamma-glutamyl carboxylase. Blood. 2007 Jun 15;109(12):5270-5. Epub 2007 Feb 27. [17327402 ]
  2. Lal S, Jada SR, Xiang X, Lim WT, Lee EJ, Chowbay B: Pharmacogenetics of target genes across the warfarin pharmacological pathway. Clin Pharmacokinet. 2006;45(12):1189-200. [17112295 ]
Target Details
64. Adenosine receptor A3
General Function:
G-protein coupled adenosine receptor activity
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. Possible role in reproduction.
Gene Name:
ADORA3
Uniprot ID:
P0DMS8
Molecular Weight:
36184.175 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.613 uMNot AvailableBindingDB 17657
References
  1. Minetti P, Tinti MO, Carminati P, Castorina M, Di Cesare MA, Di Serio S, Gallo G, Ghirardi O, Giorgi F, Giorgi L, Piersanti G, Bartoccini F, Tarzia G: 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and analogues as A2A adenosine receptor antagonists. Design, synthesis, and pharmacological characterization. J Med Chem. 2005 Nov 3;48(22):6887-96. [16250647 ]
Target Details
65. Alanine aminotransferase 1
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with precursors transported from skeletal muscles (By similarity).
Gene Name:
GPT
Uniprot ID:
P24298
Molecular Weight:
54636.415 Da
References
  1. Ohgami N, Upadhyay S, Kabata A, Morimoto K, Kusakabe H, Suzuki H: Determination of the activities of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in a microfluidic system. Biosens Bioelectron. 2007 Feb 15;22(7):1330-6. Epub 2006 Jul 18. [16854580 ]
Target Details
66. Alpha-ketoglutarate-dependent dioxygenase FTO
General Function:
Oxidative rna demethylase activity
Specific Function:
Dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. Has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. Has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine (PubMed:18775698, PubMed:20376003). Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:22002720, PubMed:26458103). Has no activity towards 1-methylguanine. Has no detectable activity towards double-stranded DNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. Contributes to the regulation of body size and body fat accumulation (PubMed:18775698, PubMed:20376003).
Gene Name:
FTO
Uniprot ID:
Q9C0B1
Molecular Weight:
58281.53 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>1000 uMNot AvailableBindingDB 17657
References
  1. Aik W, Demetriades M, Hamdan MK, Bagg EA, Yeoh KK, Lejeune C, Zhang Z, McDonough MA, Schofield CJ: Structural basis for inhibition of the fat mass and obesity associated protein (FTO). J Med Chem. 2013 May 9;56(9):3680-8. doi: 10.1021/jm400193d. Epub 2013 Apr 23. [23547775 ]
Target Details
67. Aspartate aminotransferase, cytoplasmic
General Function:
Pyridoxal phosphate binding
Specific Function:
Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain.
Gene Name:
GOT1
Uniprot ID:
P17174
Molecular Weight:
46247.14 Da
References
  1. Yudkoff M, Daikhin Y, Melo TM, Nissim I, Sonnewald U, Nissim I: The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect. Annu Rev Nutr. 2007;27:415-30. [17444813 ]
Target Details
68. Branched-chain-amino-acid aminotransferase, cytosolic
General Function:
L-valine transaminase activity
Specific Function:
Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine.
Gene Name:
BCAT1
Uniprot ID:
P54687
Molecular Weight:
42965.815 Da
References
  1. Smirnov SV, Samsonova NN, Novikova AE, Matrosov NG, Rushkevich NY, Kodera T, Ogawa J, Yamanaka H, Shimizu S: A novel strategy for enzymatic synthesis of 4-hydroxyisoleucine: identification of an enzyme possessing HMKP (4-hydroxy-3-methyl-2-keto-pentanoate) aldolase activity. FEMS Microbiol Lett. 2007 Aug;273(1):70-7. Epub 2007 Jun 6. [17559390 ]
Target Details
69. Cystine/glutamate transporter
General Function:
Cystine:glutamate antiporter activity
Specific Function:
Sodium-independent, high-affinity exchange of anionic amino acids with high specificity for anionic form of cystine and glutamate.
Gene Name:
SLC7A11
Uniprot ID:
Q9UPY5
Molecular Weight:
55422.44 Da
References
  1. Natale NR, Magnusson KR, Nelson JK: Can selective ligands for glutamate binding proteins be rationally designed? Curr Top Med Chem. 2006;6(8):823-47. [16719820 ]
Target Details
70. Glutamate receptor ionotropic, NMDA 1
General Function:
Voltage-gated cation channel activity
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors (By similarity).
Gene Name:
GRIN1
Uniprot ID:
Q05586
Molecular Weight:
105371.945 Da
References
  1. Miglio G, Dianzani C, Fallarini S, Fantozzi R, Lombardi G: Stimulation of N-methyl-D-aspartate receptors modulates Jurkat T cell growth and adhesion to fibronectin. Biochem Biophys Res Commun. 2007 Sep 21;361(2):404-9. Epub 2007 Jul 20. [17662248 ]
Target Details
71. Glutamate--cysteine ligase regulatory subunit
General Function:
Glutamate-cysteine ligase catalytic subunit binding
Specific Function:
Not Available
Gene Name:
GCLM
Uniprot ID:
P48507
Molecular Weight:
30726.745 Da
References
  1. Giordano G, White CC, McConnachie LA, Fernandez C, Kavanagh TJ, Costa LG: Neurotoxicity of domoic Acid in cerebellar granule neurons in a genetic model of glutathione deficiency. Mol Pharmacol. 2006 Dec;70(6):2116-26. Epub 2006 Sep 25. [17000861 ]
Target Details
72. Glutathione reductase, mitochondrial
General Function:
Nadp binding
Specific Function:
Maintains high levels of reduced glutathione in the cytosol.
Gene Name:
GSR
Uniprot ID:
P00390
Molecular Weight:
56256.565 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory42.7 uMNot AvailableBindingDB 17657
IC5053.7 uMNot AvailableBindingDB 17657
References
  1. Cakmak R, Durdagi S, Ekinci D, Senturk M, Topal G: Design, synthesis and biological evaluation of novel nitroaromatic compounds as potent glutathione reductase inhibitors. Bioorg Med Chem Lett. 2011 Sep 15;21(18):5398-402. doi: 10.1016/j.bmcl.2011.07.002. Epub 2011 Jul 13. [21795044 ]
Target Details
73. Metabotropic glutamate receptor 3
General Function:
Group ii metabotropic glutamate receptor activity
Specific Function:
G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity.
Gene Name:
GRM3
Uniprot ID:
Q14832
Molecular Weight:
98878.05 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory9 uMNot AvailableBindingDB 17657
References
  1. Brauner-Osborne H, Egebjerg J, Nielsen EO, Madsen U, Krogsgaard-Larsen P: Ligands for glutamate receptors: design and therapeutic prospects. J Med Chem. 2000 Jul 13;43(14):2609-45. [10893301 ]
Target Details
74. N-acetylglutamate synthase, mitochondrial
General Function:
Arginine binding
Specific Function:
Plays a role in the regulation of ureagenesis by producing the essential cofactor N-acetylglutamate (NAG), thus modulating carbamoylphosphate synthase I (CPSI) activity.
Gene Name:
NAGS
Uniprot ID:
Q8N159
Molecular Weight:
58155.835 Da
References
  1. Xu Y, Labedan B, Glansdorff N: Surprising arginine biosynthesis: a reappraisal of the enzymology and evolution of the pathway in microorganisms. Microbiol Mol Biol Rev. 2007 Mar;71(1):36-47. [17347518 ]
Target Details
75. Probable glutamate--tRNA ligase, mitochondrial
General Function:
Trna binding
Specific Function:
Catalyzes the attachment of glutamate to tRNA(Glu) in a two-step reaction: glutamate is first activated by ATP to form Glu-AMP and then transferred to the acceptor end of tRNA(Glu).
Gene Name:
EARS2
Uniprot ID:
Q5JPH6
Molecular Weight:
58688.1 Da
References
  1. Sekine S, Shichiri M, Bernier S, Chenevert R, Lapointe J, Yokoyama S: Structural bases of transfer RNA-dependent amino acid recognition and activation by glutamyl-tRNA synthetase. Structure. 2006 Dec;14(12):1791-9. [17161369 ]
Target Details
76. Tyrosine aminotransferase
General Function:
Pyridoxal phosphate binding
Specific Function:
Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity towards phenylalanine.
Gene Name:
TAT
Uniprot ID:
P17735
Molecular Weight:
50398.895 Da
References
  1. Ozturk M, Chiu CY, Akdeniz N, Jenq SF, Chang SC, Hsa CY, Jap TS: Two novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1. J Endocrinol Invest. 2006 Jun;29(6):523-7. [16840830 ]