Target Information
| Target General Information | Top | |||||
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| Target ID |
T73495
(Former ID: TTDS00122)
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| Target Name |
Glutamate receptor ionotropic kainate 1 (GRIK1)
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| Synonyms |
Glutamate receptor 5; GluR5 kainate receptor; GluR5; GluR-5; GRIK1; Excitatory amino acid receptor 3; EAA3
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| Gene Name |
GRIK1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Epilepsy/seizure [ICD-11: 8A61-8A6Z] | |||||
| 2 | Substance abuse [ICD-11: 6C40] | |||||
| 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.
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| BioChemical Class |
Glutamate-gated ion channel
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| UniProt ID | ||||||
| Sequence |
MEHGTLLAQPGLWTRDTSWALLYFLCYILPQTAPQVLRIGGIFETVENEPVNVEELAFKF
AVTSINRNRTLMPNTTLTYDIQRINLFDSFEASRRACDQLALGVAALFGPSHSSSVSAVQ SICNALEVPHIQTRWKHPSVDNKDLFYINLYPDYAAISRAILDLVLYYNWKTVTVVYEDS TGLIRLQELIKAPSRYNIKIKIRQLPSGNKDAKPLLKEMKKGKEFYVIFDCSHETAAEIL KQILFMGMMTEYYHYFFTTLDLFALDLELYRYSGVNMTGFRLLNIDNPHVSSIIEKWSME RLQAPPRPETGLLDGMMTTEAALMYDAVYMVAIASHRASQLTVSSLQCHRHKPWRLGPRF MNLIKEARWDGLTGHITFNKTNGLRKDFDLDIISLKEEGTEKAAGEVSKHLYKVWKKIGI WNSNSGLNMTDSNKDKSSNITDSLANRTLIVTTILEEPYVMYRKSDKPLYGNDRFEGYCL DLLKELSNILGFIYDVKLVPDGKYGAQNDKGEWNGMVKELIDHRADLAVAPLTITYVREK VIDFSKPFMTLGISILYRKPNGTNPGVFSFLNPLSPDIWMYVLLACLGVSCVLFVIARFT PYEWYNPHPCNPDSDVVENNFTLLNSFWFGVGALMQQGSELMPKALSTRIVGGIWWFFTL IIISSYTANLAAFLTVERMESPIDSADDLAKQTKIEYGAVRDGSTMTFFKKSKISTYEKM WAFMSSRQQTALVRNSDEGIQRVLTTDYALLMESTSIEYVTQRNCNLTQIGGLIDSKGYG VGTPIGSPYRDKITIAILQLQEEGKLHMMKEKWWRGNGCPEEDNKEASALGVENIGGIFI VLAAGLVLSVFVAIGEFIYKSRKNNDIEQAFCFFYGLQCKQTHPTNSTSGTTLSTDLECG KLIREERGIRKQSSVHTV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T39KQU | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Topiramate | Drug Info | Approved | Alcohol dependence | [2], [3], [4] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | LY293558 | Drug Info | Phase 2 | Pain | [5], [6] | |
| 2 | NS 1209 | Drug Info | Phase 2 | Neuropathic pain | [7], [8] | |
| 3 | NBQX | Drug Info | Phase 1 | Neurological disorder | [9] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | YM-90K | Drug Info | Discontinued in Phase 2 | Convulsion | [10] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Antagonist | [+] 8 Antagonist drugs | + | ||||
| 1 | Topiramate | Drug Info | [1] | |||
| 2 | 2,4-epi-neodysiherbaine | Drug Info | [13] | |||
| 3 | ACET | Drug Info | [13] | |||
| 4 | LY382884 | Drug Info | [13] | |||
| 5 | LY466195 | Drug Info | [13] | |||
| 6 | MSVIII-19 | Drug Info | [13] | |||
| 7 | NS3763 | Drug Info | [13] | |||
| 8 | UBP310 | Drug Info | [13], [21] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | LY293558 | Drug Info | [6] | |||
| 2 | NS 1209 | Drug Info | [7] | |||
| Inhibitor | [+] 14 Inhibitor drugs | + | ||||
| 1 | NBQX | Drug Info | [11] | |||
| 2 | YM-90K | Drug Info | [11] | |||
| 3 | (2S,4R)-4-(3-Methoxy-3-oxopropyl)glutamic Acid | Drug Info | [12] | |||
| 4 | 2-(3-(3-bromophenyl)ureido)-4-chlorobenzoic acid | Drug Info | [14] | |||
| 5 | 2-(3-bromobenzoylamino)-4-chlorobenzoic acid | Drug Info | [14] | |||
| 6 | 2-AMINO-3-(4-HYDROXY-1,2,5-OXADIAZOL-3-YL)PROPIONIC ACID (STRUCTURAL MIX) | Drug Info | [15] | |||
| 7 | 2S,4R-4-METHYLGLUTAMATE | Drug Info | [12] | |||
| 8 | DIHYDROKAINATE | Drug Info | [16] | |||
| 9 | DNQX | Drug Info | [17] | |||
| 10 | Domoric acid | Drug Info | [12] | |||
| 11 | S-ATPO | Drug Info | [18] | |||
| 12 | TQX-173 | Drug Info | [19] | |||
| 13 | UBP-302 | Drug Info | [20] | |||
| 14 | [3H]quisqualate | Drug Info | [12] | |||
| Agonist | [+] 9 Agonist drugs | + | ||||
| 1 | (S)-4-AHCP | Drug Info | [13] | |||
| 2 | (S)-5-iodowillardiine | Drug Info | [13] | |||
| 3 | 8-deoxy-neodysiherbaine | Drug Info | [13] | |||
| 4 | ATPA | Drug Info | [13] | |||
| 5 | domoic acid | Drug Info | [13] | |||
| 6 | dysiherbaine | Drug Info | [13] | |||
| 7 | LY339434 | Drug Info | [13] | |||
| 8 | SYM2081 | Drug Info | [13] | |||
| 9 | [3H]kainate | Drug Info | [12], [13] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| 2 | Glutamatergic synapse | |||||
| Panther Pathway | [+] 4 Panther Pathways | + | ||||
| 1 | Huntington disease | |||||
| 2 | Ionotropic glutamate receptor pathway | |||||
| 3 | Metabotropic glutamate receptor group III pathway | |||||
| 4 | Metabotropic glutamate receptor group I pathway | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Development of medications for alcohol use disorders: recent advances and ongoing challenges. Expert Opin Emerg Drugs. 2005 May;10(2):323-43. | |||||
| 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: 6849). | |||||
| REF 3 | Use of second-generation antiepileptic drugs in the pediatric population. Paediatr Drugs. 2008;10(4):217-54. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | 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: 4245). | |||||
| REF 6 | Pharmacogenetics of new analgesics. Br J Pharmacol. 2011 Jun;163(3):447-60. | |||||
| REF 7 | 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. | |||||
| REF 8 | Emerging drugs for epilepsy. Expert Opin Emerg Drugs. 2007 Sep;12(3):407-22. | |||||
| REF 9 | 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 10 | 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 11 | 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. | |||||
| REF 12 | 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. | |||||
| REF 13 | 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). | |||||
| REF 14 | 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. | |||||
| REF 15 | 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. | |||||
| REF 16 | 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. | |||||
| REF 17 | 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 18 | 3-Substituted phenylalanines as selective AMPA- and kainate receptor ligands. Bioorg Med Chem. 2009 Sep 1;17(17):6390-401. | |||||
| REF 19 | 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. | |||||
| REF 20 | 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 21 | Mapping 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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