Target Information

Target General Infomation
Target ID
T73495
Former ID
TTDS00122
Target Name
Glutamate receptor, ionotropic kainate 1
Gene Name
GRIK1
Synonyms
EAA3; Excitatory amino acid receptor 3; GluR-5; GluR5; GluR5 kainate receptor; Glutamate receptor 5; GRIK1
Target Type
Successful
Disease Convulsions [ICD9: 780.3; ICD10: R56.0]
Epilepsy; Alcohol use disorders [ICD9:303; ICD10: G40, F10.2]
Epilepsy; Neuropathic pain [ICD9:356.0, 356.8; ICD10: G40, G64, G90.0]
Neurological disease [ICD9: 338, 338.2, 410, 782.3,780; ICD10: I21, I22, R52, R52.1-R52.2, R60.9, G89]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
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 tothe 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.
BioChemical Class
Glutamate-gated ion channel
Target Validation
T73495
UniProt ID
P39086
Sequence
MEHGTLLAQPGLWTRDTSWALLYFLCYILPQTAPQVLRIGGIFETVENEPVNVEELAFKF
AVTSINRNRTLMPNTTLTYDIQRINLFDSFEASRRACDQLALGVAALFGPSHSSSVSAVQ
SICNALEVPHIQTRWKHPSVDNKDLFYINLYPDYAAISRAILDLVLYYNWKTVTVVYEDS
TGLIRLQELIKAPSRYNIKIKIRQLPSGNKDAKPLLKEMKKGKEFYVIFDCSHETAAEIL
KQILFMGMMTEYYHYFFTTLDLFALDLELYRYSGVNMTGFRLLNIDNPHVSSIIEKWSME
RLQAPPRPETGLLDGMMTTEAALMYDAVYMVAIASHRASQLTVSSLQCHRHKPWRLGPRF
MNLIKEARWDGLTGHITFNKTNGLRKDFDLDIISLKEEGTEKAAGEVSKHLYKVWKKIGI
WNSNSGLNMTDSNKDKSSNITDSLANRTLIVTTILEEPYVMYRKSDKPLYGNDRFEGYCL
DLLKELSNILGFIYDVKLVPDGKYGAQNDKGEWNGMVKELIDHRADLAVAPLTITYVREK
VIDFSKPFMTLGISILYRKPNGTNPGVFSFLNPLSPDIWMYVLLACLGVSCVLFVIARFT
PYEWYNPHPCNPDSDVVENNFTLLNSFWFGVGALMQQGSELMPKALSTRIVGGIWWFFTL
IIISSYTANLAAFLTVERMESPIDSADDLAKQTKIEYGAVRDGSTMTFFKKSKISTYEKM
WAFMSSRQQTALVRNSDEGIQRVLTTDYALLMESTSIEYVTQRNCNLTQIGGLIDSKGYG
VGTPIGSPYRDKITIAILQLQEEGKLHMMKEKWWRGNGCPEEDNKEASALGVENIGGIFI
VLAAGLVLSVFVAIGEFIYKSRKNNDIEQAFCFFYGLQCKQTHPTNSTSGTTLSTDLECG
KLIREERGIRKQSSVHTV
Drugs and Mode of Action
Drug(s) Topiramate Drug Info Approved Epilepsy; Alcohol use disorders [1], [2], [3]
LY293558 Drug Info Phase 2 Pain [4], [5]
NS 1209 Drug Info Phase 2 Epilepsy; Neuropathic pain [6], [7]
NBQX Drug Info Phase 1 Neurological disease [8]
YM-90K Drug Info Discontinued in Phase 2 Convulsions [9]
Inhibitor (2S,4R)-4-(3-Methoxy-3-oxopropyl)glutamic Acid Drug Info [10]
(R,S)-AMPA Drug Info [11]
2-(3-(3-bromophenyl)ureido)-4-chlorobenzoic acid Drug Info [12]
2-(3-bromobenzoylamino)-4-chlorobenzoic acid Drug Info [12]
2-AMINO-3-(4-HYDROXY-1,2,5-OXADIAZOL-3-YL)PROPIONIC ACID (STRUCTURAL MIX) Drug Info [13]
2S,4R-4-METHYLGLUTAMATE Drug Info [10]
DIHYDROKAINATE Drug Info [14]
DNQX Drug Info [15]
Domoric acid Drug Info [10]
GLUTAMATE Drug Info [13]
KAINATE Drug Info [10]
NBQX Drug Info [16]
QUISQUALATE Drug Info [10]
S-ATPO Drug Info [17]
TQX-173 Drug Info [18]
UBP-302 Drug Info [19]
YM-90K Drug Info [16]
Agonist (S)-4-AHCP Drug Info [20]
(S)-5-iodowillardiine Drug Info [20]
8-deoxy-neodysiherbaine Drug Info [20]
ATPA Drug Info [20]
domoic acid Drug Info [20]
dysiherbaine Drug Info [20]
LY339434 Drug Info [20]
SYM2081 Drug Info [20]
[3H](2S,4R)-4-methylglutamate Drug Info [20]
[3H]kainate Drug Info [20]
Antagonist 2,4-epi-neodysiherbaine Drug Info [20]
ACET Drug Info [20]
LY382884 Drug Info [20]
LY466195 Drug Info [20]
MSVIII-19 Drug Info [20]
NS3763 Drug Info [20]
Topiramate Drug Info [21]
UBP310 Drug Info [20]
[3H]UBP310 Drug Info [22]
Modulator LY293558 Drug Info [5]
NS 1209 Drug Info [6]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
Glutamatergic synapse
PANTHER Pathway Huntington disease
Ionotropic glutamate receptor pathway
Metabotropic glutamate receptor group III pathway
Metabotropic glutamate receptor group I pathway
WikiPathways Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
References
REF 1Use of second-generation antiepileptic drugs in the pediatric population. Paediatr Drugs. 2008;10(4):217-54.
REF 2(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6849).
REF 3Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 4(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4245).
REF 5Pharmacogenetics of new analgesics. Br J Pharmacol. 2011 Jun;163(3):447-60.
REF 6The efficacy of the AMPA receptor antagonist NS1209 and lidocaine in nerve injury pain: a randomized, double-blind, placebo-controlled, three-way crossover study. Anesth Analg. 2009 Apr;108(4):1311-9.
REF 7Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007 Sep;12(3):407-22.
REF 8(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4264).
REF 9Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002155)
REF 10J Med Chem. 2008 Jul 24;51(14):4093-103. Epub 2008 Jun 25.Chemo-enzymatic synthesis of a series of 2,4-syn-functionalized (S)-glutamate analogues: new insight into the structure-activity relation ofionotropic glutamate receptor subtypes 5, 6, and 7.
REF 11J Med Chem. 2008 Oct 23;51(20):6614-8. Epub 2008 Sep 24.1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. structure-activity relationships and identification of potent and Selective iGluR5 modulators.
REF 12J Med Chem. 2004 Dec 30;47(27):6948-57.Bioisosteric modifications of 2-arylureidobenzoic acids: selective noncompetitive antagonists for the homomeric kainate receptor subtype GluR5.
REF 13J Med Chem. 2010 May 27;53(10):4110-8.4-hydroxy-1,2,5-oxadiazol-3-yl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and molecular pharmacological characterization at ionotropic glutamate receptors of compounds related to glutamate and its homologues.
REF 14J Med Chem. 2008 Jul 24;51(14):4085-92. Epub 2008 Jun 25.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.
REF 15J Med Chem. 1996 Oct 25;39(22):4430-8.Synthesis of chiral 1-(2'-amino-2'-carboxyethyl)-1,4-dihydro-6,7-quinoxaline-2,3-diones: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor agonists and antagonists.
REF 16Bioorg Med Chem Lett. 2000 May 15;10(10):1133-7.4,10-Dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-carboxylic acid derivatives: highly potent and selective AMPA receptors antagonists with in vivo activity.
REF 17Bioorg Med Chem. 2009 Sep 1;17(17):6390-401. Epub 2009 Jul 16.3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands.
REF 18J Med Chem. 2001 Sep 13;44(19):3157-65.Synthesis, ionotropic glutamate receptor binding affinity, and structure-activity relationships of a new set of 4,5-dihydro-8-heteroaryl-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2-carboxylates analogues of TQX-173.
REF 19J Med Chem. 2006 Oct 5;49(20):6015-26.Structural investigation of the 7-chloro-3-hydroxy-1H-quinazoline-2,4-dione scaffold to obtain AMPA and kainate receptor selective antagonists. Synthesis, pharmacological, and molecular modeling studies.
REF 20(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 450).
REF 21Development of medications for alcohol use disorders: recent advances and ongoing challenges. Expert Opin Emerg Drugs. 2005 May;10(2):323-43.
REF 22Mapping the ligand binding sites of kainate receptors: molecular determinants of subunit-selective binding of the antagonist [3H]UBP310. Mol Pharmacol. 2010 Dec;78(6):1036-45.

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