General Information of Drug Therapeutic Target (DTT) (ID: TT0MYE2)

DTT Name Glutamate receptor ionotropic kainate 1 (GRIK1)
Synonyms Glutamate receptor 5; GluR5 kainate receptor; GluR5; GluR-5; GRIK1; Excitatory amino acid receptor 3; EAA3
Gene Name GRIK1
DTT Type
Successful target
[1]
BioChemical Class
Glutamate-gated ion channel
UniProt ID
GRIK1_HUMAN
TTD ID
T73495
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MEHGTLLAQPGLWTRDTSWALLYFLCYILPQTAPQVLRIGGIFETVENEPVNVEELAFKF
AVTSINRNRTLMPNTTLTYDIQRINLFDSFEASRRACDQLALGVAALFGPSHSSSVSAVQ
SICNALEVPHIQTRWKHPSVDNKDLFYINLYPDYAAISRAILDLVLYYNWKTVTVVYEDS
TGLIRLQELIKAPSRYNIKIKIRQLPSGNKDAKPLLKEMKKGKEFYVIFDCSHETAAEIL
KQILFMGMMTEYYHYFFTTLDLFALDLELYRYSGVNMTGFRLLNIDNPHVSSIIEKWSME
RLQAPPRPETGLLDGMMTTEAALMYDAVYMVAIASHRASQLTVSSLQCHRHKPWRLGPRF
MNLIKEARWDGLTGHITFNKTNGLRKDFDLDIISLKEEGTEKAAGEVSKHLYKVWKKIGI
WNSNSGLNMTDSNKDKSSNITDSLANRTLIVTTILEEPYVMYRKSDKPLYGNDRFEGYCL
DLLKELSNILGFIYDVKLVPDGKYGAQNDKGEWNGMVKELIDHRADLAVAPLTITYVREK
VIDFSKPFMTLGISILYRKPNGTNPGVFSFLNPLSPDIWMYVLLACLGVSCVLFVIARFT
PYEWYNPHPCNPDSDVVENNFTLLNSFWFGVGALMQQGSELMPKALSTRIVGGIWWFFTL
IIISSYTANLAAFLTVERMESPIDSADDLAKQTKIEYGAVRDGSTMTFFKKSKISTYEKM
WAFMSSRQQTALVRNSDEGIQRVLTTDYALLMESTSIEYVTQRNCNLTQIGGLIDSKGYG
VGTPIGSPYRDKITIAILQLQEEGKLHMMKEKWWRGNGCPEEDNKEASALGVENIGGIFI
VLAAGLVLSVFVAIGEFIYKSRKNNDIEQAFCFFYGLQCKQTHPTNSTSGTTLSTDLECG
KLIREERGIRKQSSVHTV
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.
KEGG Pathway
Neuroactive ligand-receptor interaction (hsa04080 )
Glutamatergic synapse (hsa04724 )
Reactome Pathway
Activation of Ca-permeable Kainate Receptor (R-HSA-451308 )
Activation of Na-permeable kainate receptors (R-HSA-451307 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Topiramate DM82Z30 Alcohol dependence 6C40.2 Approved [1]
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3 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
LY293558 DM4N6EK Pain MG30-MG3Z Phase 2 [2]
NS 1209 DM9EFH0 Epilepsy 8A60-8A68 Phase 2 [3]
NBQX DMPHZI5 Neurological disorder 6B60 Phase 1 [4]
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1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
YM-90K DMWRT4L Convulsion 8A68.Z Discontinued in Phase 2 [4]
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28 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(2S,4R)-4-(3-Methoxy-3-oxopropyl)glutamic Acid DMTQF2G Discovery agent N.A. Investigative [5]
(S)-4-AHCP DMN9YXL Discovery agent N.A. Investigative [6]
(S)-5-iodowillardiine DM1DNRP Discovery agent N.A. Investigative [6]
2,4-epi-neodysiherbaine DMZRY0Q Discovery agent N.A. Investigative [6]
2-(3-(3-bromophenyl)ureido)-4-chlorobenzoic acid DMRX4HM Discovery agent N.A. Investigative [7]
2-(3-bromobenzoylamino)-4-chlorobenzoic acid DMX4DUR Discovery agent N.A. Investigative [7]
2-AMINO-3-(4-HYDROXY-1,2,5-OXADIAZOL-3-YL)PROPIONIC ACID (STRUCTURAL MIX) DMQKGL3 Discovery agent N.A. Investigative [8]
2S,4R-4-METHYLGLUTAMATE DMNU1YR Discovery agent N.A. Investigative [5]
8-deoxy-neodysiherbaine DM7YW3B Discovery agent N.A. Investigative [6]
ACET DMB2463 Discovery agent N.A. Investigative [6]
ATPA DM2DAFS Discovery agent N.A. Investigative [6]
DIHYDROKAINATE DM9NO6F Discovery agent N.A. Investigative [9]
DNQX DMQXPA5 Discovery agent N.A. Investigative [10]
domoic acid DMYPVO0 Discovery agent N.A. Investigative [6]
Domoric acid DMOJF6D Discovery agent N.A. Investigative [5]
dysiherbaine DM0EBAF Discovery agent N.A. Investigative [6]
LY339434 DM8S7AO Discovery agent N.A. Investigative [6]
LY382884 DMWKYFO Discovery agent N.A. Investigative [6]
LY466195 DM97NBO Discovery agent N.A. Investigative [6]
MSVIII-19 DM4KM91 Discovery agent N.A. Investigative [6]
NS3763 DMVL5KS Discovery agent N.A. Investigative [6]
S-ATPO DMJQVAG Discovery agent N.A. Investigative [11]
SYM2081 DM30WDL Discovery agent N.A. Investigative [6]
TQX-173 DMZA6X3 Discovery agent N.A. Investigative [12]
UBP-302 DMSJLX0 Discovery agent N.A. Investigative [13]
UBP310 DMVQL3J Discovery agent N.A. Investigative [6]
[3H]kainate DMMK7XU Discovery agent N.A. Investigative [6]
[3H]quisqualate DMDQBTX Discovery agent N.A. Investigative [5]
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⏷ Show the Full List of 28 Investigative Drug(s)

References

1 Development of medications for alcohol use disorders: recent advances and ongoing challenges. Expert Opin Emerg Drugs. 2005 May;10(2):323-43.
2 Pharmacogenetics of new analgesics. Br J Pharmacol. 2011 Jun;163(3):447-60.
3 The 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.
4 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... Bioorg Med Chem Lett. 2000 May 15;10(10):1133-7.
5 Chemo-enzymatic synthesis of a series of 2,4-syn-functionalized (S)-glutamate analogues: new insight into the structure-activity relation of ionotr... J Med Chem. 2008 Jul 24;51(14):4093-103.
6 URL: 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).
7 Bioisosteric modifications of 2-arylureidobenzoic acids: selective noncompetitive antagonists for the homomeric kainate receptor subtype GluR5. J Med Chem. 2004 Dec 30;47(27):6948-57.
8 4-hydroxy-1,2,5-oxadiazol-3-yl moiety as bioisoster of the carboxy function. Synthesis, ionization constants, and molecular pharmacological charact... J Med Chem. 2010 May 27;53(10):4110-8.
9 Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid: a novel selective inhibitor of human exci... J Med Chem. 2008 Jul 24;51(14):4085-92.
10 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 recep... J Med Chem. 1996 Oct 25;39(22):4430-8.
11 3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands. Bioorg Med Chem. 2009 Sep 1;17(17):6390-401.
12 Synthesis, ionotropic glutamate receptor binding affinity, and structure-activity relationships of a new set of 4,5-dihydro-8-heteroaryl-4-oxo-1,2,... J Med Chem. 2001 Sep 13;44(19):3157-65.
13 Structural investigation of the 7-chloro-3-hydroxy-1H-quinazoline-2,4-dione scaffold to obtain AMPA and kainate receptor selective antagonists. Syn... J Med Chem. 2006 Oct 5;49(20):6015-26.