Target General Infomation
Target ID
T33584 (Former ID: TTDC00250)
Target Name
Glutamate receptor AMPA 1 (GRIA1)
Synonyms
Glutamate receptor ionotropic, AMPA 1; Glutamate receptor 1; GluR-K1; GluR-A; GluR-1; GluA1; GLUR1; GLUH1; AMPA-selective glutamate receptor 1
Gene Name
GRIA1
Target Type
Successful target
[1]
Disease [+] 1 Target-related Diseases +
1 Neuropathy [ICD-11: 8C0Z]
Function
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. Ionotropic glutamate receptor.
BioChemical Class
Glutamate-gated ion channel
UniProt ID
GRIA1_HUMAN
Sequence
MQHIFAFFCTGFLGAVVGANFPNNIQIGGLFPNQQSQEHAAFRFALSQLTEPPKLLPQID
IVNISDSFEMTYRFCSQFSKGVYAIFGFYERRTVNMLTSFCGALHVCFITPSFPVDTSNQ
FVLQLRPELQDALISIIDHYKWQKFVYIYDADRGLSVLQKVLDTAAEKNWQVTAVNILTT
TEEGYRMLFQDLEKKKERLVVVDCESERLNAILGQIIKLEKNGIGYHYILANLGFMDIDL
NKFKESGANVTGFQLVNYTDTIPAKIMQQWKNSDARDHTRVDWKRPKYTSALTYDGVKVM
AEAFQSLRRQRIDISRRGNAGDCLANPAVPWGQGIDIQRALQQVRFEGLTGNVQFNEKGR
RTNYTLHVIEMKHDGIRKIGYWNEDDKFVPAATDAQAGGDNSSVQNRTYIVTTILEDPYV
MLKKNANQFEGNDRYEGYCVELAAEIAKHVGYSYRLEIVSDGKYGARDPDTKAWNGMVGE
LVYGRADVAVAPLTITLVREEVIDFSKPFMSLGISIMIKKPQKSKPGVFSFLDPLAYEIW
MCIVFAYIGVSVVLFLVSRFSPYEWHSEEFEEGRDQTTSDQSNEFGIFNSLWFSLGAFMQ
QGCDISPRSLSGRIVGGVWWFFTLIIISSYTANLAAFLTVERMVSPIESAEDLAKQTEIA
YGTLEAGSTKEFFRRSKIAVFEKMWTYMKSAEPSVFVRTTEEGMIRVRKSKGKYAYLLES
TMNEYIEQRKPCDTMKVGGNLDSKGYGIATPKGSALRNPVNLAVLKLNEQGLLDKLKNKW
WYDKGECGSGGGDSKDKTSALSLSNVAGVFYILIGGLGLAMLVALIEFCYKSRSESKRMK
GFCLIPQQSINEAIRTSTLPRNSGAGASSGGSGENGRVVSHDFPKSMQSIPCMSHSSGMP
LGATGL
Drugs and Modes of Action
Approved Drug(s) [+] 1 Approved Drugs +
1 E-2007 Drug Info Approved Diabetic neuropathy [2], [3]
Clinical Trial Drug(s) [+] 1 Clinical Trial Drugs +
1 NBQX Drug Info Phase 1 Neurological disorder [4]
Discontinued Drug(s) [+] 4 Discontinued Drugs +
1 YM-90K Drug Info Discontinued in Phase 2 Convulsion [5]
2 Farampator Drug Info Discontinued in Phase 1 Schizophrenia [6]
3 GYKI-52466 Drug Info Terminated Alzheimer disease [7], [8]
4 SORETOLIDE Drug Info Terminated Convulsion [9]
Mode of Action [+] 6 Modes of Action +
Inhibitor [+] 18 Inhibitor drugs +
1 E-2007 Drug Info [1]
2 NBQX Drug Info [10]
3 YM-90K Drug Info [11]
4 GYKI-52466 Drug Info [13]
5 GYKI-53655 Drug Info [14]
6 ZONAMPANEL Drug Info [11]
7 (R,S)-AMPA Drug Info [16], [17]
8 (S)-AMPA Drug Info [18]
9 (S)-WILLARDIINE Drug Info [19]
10 7-chloro-3-hydroxyquinazoline-2,4-dione Drug Info [10]
11 Argiotoxin-636 Drug Info [20]
12 DNQX Drug Info [21]
13 GLUTAMATE Drug Info [17]
14 N-(4-hydroxyphenylpropanyl)-spermine Drug Info [20]
15 Philanthotoxin-343 Drug Info [20]
16 Piriqualone Drug Info [22]
17 RPR-118723 Drug Info [23]
18 [3H]kainate Drug Info [17]
Binder [+] 1 Binder drugs +
1 Farampator Drug Info [12]
Modulator [+] 1 Modulator drugs +
1 SORETOLIDE Drug Info [15]
Agonist [+] 2 Agonist drugs +
1 (S)-5-fluorowillardiine Drug Info [16]
2 [3H]AMPA Drug Info [16]
Antagonist [+] 2 Antagonist drugs +
1 ATPO Drug Info [16]
2 [3H]CNQX Drug Info [16], [24]
Blocker (channel blocker) [+] 1 Blocker (channel blocker) drugs +
1 joro toxin Drug Info [16]
Target Regulators
Target-interacting Proteins
Target Profiles in Patients
Target Expression
 Profile (TEP)
Target Affiliated Biological Pathways
KEGG Pathway [+] 11 KEGG Pathways +
1 cAMP signaling pathway
2 Neuroactive ligand-receptor interaction
3 Circadian entrainment
4 Long-term potentiation
5 Retrograde endocannabinoid signaling
6 Glutamatergic synapse
7 Dopaminergic synapse
8 Long-term depression
9 Amyotrophic lateral sclerosis (ALS)
10 Amphetamine addiction
11 Nicotine addiction
Panther Pathway [+] 2 Panther Pathways +
1 Ionotropic glutamate receptor pathway
2 Metabotropic glutamate receptor group III pathway
PID Pathway [+] 1 PID Pathways +
1 EPHB forward signaling
Reactome [+] 5 Reactome Pathways +
1 COPII (Coat Protein 2) Mediated Vesicle Transport
2 Trafficking of AMPA receptors
3 Trafficking of GluR2-containing AMPA receptors
4 Unblocking of NMDA receptor, glutamate binding and activation
5 Cargo concentration in the ER
WikiPathways [+] 4 WikiPathways +
1 Hypothetical Network for Drug Addiction
2 Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
3 Amyotrophic lateral sclerosis (ALS)
4 BDNF signaling pathway
Target-Related Models and Studies
Target Validation
References
REF 1 Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
REF 2 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. (Ligand id: 7050).
REF 3 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
REF 4 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. (Ligand id: 4264).
REF 5 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002155)
REF 6 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012259)
REF 7 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. (Ligand id: 4210).
REF 8 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005470)
REF 9 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002789)
REF 10 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.
REF 11 Synthesis and AMPA receptor antagonistic activity of a novel 7-imidazolyl-6-trifluoromethyl quinoxalinecarboxylic acid with a substituted phenyl gr... Bioorg Med Chem Lett. 2004 Oct 18;14(20):5107-11.
REF 12 The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
REF 13 New 7,8-ethylenedioxy-2,3-benzodiazepines as noncompetitive AMPA receptor antagonists. Bioorg Med Chem Lett. 2006 Jan 1;16(1):167-70.
REF 14 Substituted 1,2-dihydrophthalazines: potent, selective, and noncompetitive inhibitors of the AMPA receptor. J Med Chem. 1996 Jan 19;39(2):343-6.
REF 15 Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist. Acta Neurol Scand Suppl. 2013;(197):19-24.
REF 16 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: 444).
REF 17 1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. structure-activity relationships and identification of pot... J Med Chem. 2008 Oct 23;51(20):6614-8.
REF 18 Synthesis and pharmacology of willardiine derivatives acting as antagonists of kainate receptors. J Med Chem. 2005 Dec 1;48(24):7867-81.
REF 19 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.
REF 20 Developing a complete pharmacology for AMPA receptors: a perspective on subtype-selective ligands. Bioorg Med Chem. 2010 Feb 15;18(4):1381-7.
REF 21 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.
REF 22 Atropisomeric quinazolin-4-one derivatives are potent noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antag... Bioorg Med Chem Lett. 2001 Jan 22;11(2):177-81.
REF 23 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. J Med Chem. 2000 Jun 15;43(12):2371-81.
REF 24 Structure-activity relationship studies on N3-substituted willardiine derivatives acting as AMPA or kainate receptor antagonists. J Med Chem. 2006 Apr 20;49(8):2579-92.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Wang and Dr. Li.