Target Information

Target General Infomation
Target ID
T33584
Former ID
TTDC00250
Target Name
Glutamate receptor 1
Gene Name
GRIA1
Synonyms
AMPA-selective glutamate receptor 1; GluR-1; GluR-A; GluR-K1; Glutamate receptor ionotropic, AMPA 1; GRIA1
Target Type
Clinical Trial
Disease Alzheimer disease [ICD9: 331; ICD10: G30]
Convulsions [ICD9: 780.3; ICD10: R56.0]
Major depressive disorder; Schizophrenia [ICD9:296.2, 296.3, 710.0, 295; ICD10: F32, F33, M32, F20]
Neurological disease [ICD9: 338, 338.2, 410, 782.3,780; ICD10: I21, I22, R52, R52.1-R52.2, R60.9, G89]
Function
Ionotropic glutamate receptor. L-glutamateacts 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 ofthe 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.
BioChemical Class
Glutamate-gated ion channel
Target Validation
T33584
UniProt ID
P42261
Sequence
MQHIFAFFCTGFLGAVVGANFPNNIQIGGLFPNQQSQEHAAFRFALSQLTEPPKLLPQID
IVNISDSFEMTYRFCSQFSKGVYAIFGFYERRTVNMLTSFCGALHVCFITPSFPVDTSNQ
FVLQLRPELQDALISIIDHYKWQKFVYIYDADRGLSVLQKVLDTAAEKNWQVTAVNILTT
TEEGYRMLFQDLEKKKERLVVVDCESERLNAILGQIIKLEKNGIGYHYILANLGFMDIDL
NKFKESGANVTGFQLVNYTDTIPAKIMQQWKNSDARDHTRVDWKRPKYTSALTYDGVKVM
AEAFQSLRRQRIDISRRGNAGDCLANPAVPWGQGIDIQRALQQVRFEGLTGNVQFNEKGR
RTNYTLHVIEMKHDGIRKIGYWNEDDKFVPAATDAQAGGDNSSVQNRTYIVTTILEDPYV
MLKKNANQFEGNDRYEGYCVELAAEIAKHVGYSYRLEIVSDGKYGARDPDTKAWNGMVGE
LVYGRADVAVAPLTITLVREEVIDFSKPFMSLGISIMIKKPQKSKPGVFSFLDPLAYEIW
MCIVFAYIGVSVVLFLVSRFSPYEWHSEEFEEGRDQTTSDQSNEFGIFNSLWFSLGAFMQ
QGCDISPRSLSGRIVGGVWWFFTLIIISSYTANLAAFLTVERMVSPIESAEDLAKQTEIA
YGTLEAGSTKEFFRRSKIAVFEKMWTYMKSAEPSVFVRTTEEGMIRVRKSKGKYAYLLES
TMNEYIEQRKPCDTMKVGGNLDSKGYGIATPKGSALRNPVNLAVLKLNEQGLLDKLKNKW
WYDKGECGSGGGDSKDKTSALSLSNVAGVFYILIGGLGLAMLVALIEFCYKSRSESKRMK
GFCLIPQQSINEAIRTSTLPRNSGAGASSGGSGENGRVVSHDFPKSMQSIPCMSHSSGMP
LGATGL
Drugs and Mode of Action
Drug(s) NBQX Drug Info Phase 1 Neurological disease [467600]
YM-90K Drug Info Discontinued in Phase 2 Convulsions [545107]
Farampator Drug Info Discontinued in Phase 1 Major depressive disorder; Schizophrenia [547029]
GYKI-52466 Drug Info Terminated Alzheimer disease [467544], [545950]
GYKI-53655 Drug Info Terminated Discovery agent [467543], [546685]
SORETOLIDE Drug Info Terminated Convulsions [545313]
ZONAMPANEL Drug Info Terminated Discovery agent [546621]
Inhibitor (R,S)-AMPA Drug Info [529714]
(S)-AMPA Drug Info [527890]
(S)-WILLARDIINE Drug Info [534502]
6-cyano-7-nitroquinoxaline-2,3-dione Drug Info [528135]
7-chloro-3-hydroxyquinazoline-2,4-dione Drug Info [528453]
Argiotoxin-636 Drug Info [530651]
DNQX Drug Info [534261]
GLUTAMATE Drug Info [529714]
GYKI-52466 Drug Info [527792]
GYKI-53655 Drug Info [534085]
KAINATE Drug Info [529714]
N-(4-hydroxyphenylpropanyl)-spermine Drug Info [530651]
NBQX Drug Info [528453]
Philanthotoxin-343 Drug Info [530651]
Piriqualone Drug Info [525977]
RPR-118723 Drug Info [525816]
YM-90K Drug Info [527219]
ZONAMPANEL Drug Info [527219]
Agonist (S)-5-fluorowillardiine Drug Info [543827]
AMPA Drug Info [543827]
[3H]AMPA Drug Info [543827]
Antagonist ATPO Drug Info [543827]
[3H]CNQX Drug Info [543827]
Binder Farampator Drug Info [536463]
Blocker (channel blocker) joro toxin Drug Info [543827]
Modulator SORETOLIDE Drug Info [532262]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway cAMP signaling pathway
Neuroactive ligand-receptor interaction
Circadian entrainment
Long-term potentiation
Retrograde endocannabinoid signaling
Glutamatergic synapse
Dopaminergic synapse
Long-term depression
Amyotrophic lateral sclerosis (ALS)
Amphetamine addiction
Nicotine addiction
PANTHER Pathway Ionotropic glutamate receptor pathway
Metabotropic glutamate receptor group III pathway
Pathway Interaction Database EPHB forward signaling
Reactome COPII (Coat Protein 2) Mediated Vesicle Transport
Trafficking of AMPA receptors
Trafficking of GluR2-containing AMPA receptors
Unblocking of NMDA receptor, glutamate binding and activation
Cargo concentration in the ER
WikiPathways Hypothetical Network for Drug Addiction
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
Amyotrophic lateral sclerosis (ALS)
BDNF signaling pathway
References
Ref 467543(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: 4209).
Ref 467544(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: 4210).
Ref 467600(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 545107Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002155)
Ref 545313Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002789)
Ref 545950Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005470)
Ref 546621Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009224)
Ref 546685Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800009633)
Ref 547029Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012259)
Ref 525816J Med Chem. 2000 Jun 15;43(12):2371-81.Indeno[1,2-b]pyrazin-2,3-diones: a new class of antagonists at the glycine site of the NMDA receptor with potent in vivo activity.
Ref 525977Bioorg Med Chem Lett. 2001 Jan 22;11(2):177-81.Atropisomeric quinazolin-4-one derivatives are potent noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists.
Ref 527219Bioorg Med Chem Lett. 2004 Oct 18;14(20):5107-11.Synthesis and AMPA receptor antagonistic activity of a novel 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acid with a substituted phenyl groupand improved its good physicochemical properties by introduced CF3 group.
Ref 527792Bioorg Med Chem Lett. 2006 Jan 1;16(1):167-70. Epub 2005 Oct 10.New 7,8-ethylenedioxy-2,3-benzodiazepines as noncompetitive AMPA receptor antagonists.
Ref 527890J Med Chem. 2005 Dec 1;48(24):7867-81.Synthesis and pharmacology of willardiine derivatives acting as antagonists of kainate receptors.
Ref 528135J Med Chem. 2006 Apr 20;49(8):2579-92.Structure-activity relationship studies on N3-substituted willardiine derivatives acting as AMPA or kainate receptor antagonists.
Ref 528453J 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 529714J 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 530651Bioorg Med Chem. 2010 Feb 15;18(4):1381-7. Epub 2010 Jan 6.Developing a complete pharmacology for AMPA receptors: a perspective on subtype-selective ligands.
Ref 532262Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand Suppl. 2013;(197):19-24.
Ref 534085J Med Chem. 1996 Jan 19;39(2):343-6.Substituted 1,2-dihydrophthalazines: potent, selective, and noncompetitive inhibitors of the AMPA receptor.
Ref 534261J 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 534502J Med Chem. 1997 Oct 24;40(22):3645-50.Synthesis of willardiine and 6-azawillardiine analogs: pharmacological characterization on cloned homomeric human AMPA and kainate receptor subtypes.
Ref 536463The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. Epub 2007 Jul 31.
Ref 543827(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: 444).

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