Details of the Drug Therapeutic Target (DTT)
General Information of Drug Therapeutic Target (DTT) (ID: TTVBPDM)
DTT Name | Metabotropic glutamate receptor 1 (mGluR1) | ||||
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Synonyms | mGLUR1; Glutamate receptor mGLU1; GPRC1A | ||||
Gene Name | GRM1 | ||||
DTT Type |
Discontinued target
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[1] | |||
BioChemical Class |
GPCR glutamate
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UniProt ID | |||||
TTD ID | |||||
3D Structure | |||||
Sequence |
MVGLLLFFFPAIFLEVSLLPRSPGRKVLLAGASSQRSVARMDGDVIIGALFSVHHQPPAE
KVPERKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSI EFIRDSLISIRDEKDGINRCLPDGQSLPPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDI PQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESG MDAFKELAAQEGLCIAHSDKIYSNAGEKSFDRLLRKLRERLPKARVVVCFCEGMTVRGLL SAMRRLGVVGEFSLIGSDGWADRDEVIEGYEVEANGGITIKLQSPEVRSFDDYFLKLRLD TNTRNPWFPEFWQHRFQCRLPGHLLENPNFKRICTGNESLEENYVQDSKMGFVINAIYAM AHGLQNMHHALCPGHVGLCDAMKPIDGSKLLDFLIKSSFIGVSGEEVWFDEKGDAPGRYD IMNLQYTEANRYDYVHVGTWHEGVLNIDDYKIQMNKSGVVRSVCSEPCLKGQIKVIRKGE VSCCWICTACKENEYVQDEFTCKACDLGWWPNADLTGCEPIPVRYLEWSNIESIIAIAFS CLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQ RLLVGLSSAMCYSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVIIASILISVQLTL VVTLIIMEPPMPILSYPSIKEVYLICNTSNLGVVAPLGYNGLLIMSCTYYAFKTRNVPAN FNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCMFTPKMYIIIA KPERNVRSAFTTSDVVRMHVGDGKLPCRSNTFLNIFRRKKAGAGNANSNGKSVSWSEPGG GQVPKGQHMWHRLSVHVKTNETACNQTAVIKPLTKSYQGSGKSLTFSDTSTKTLYNVEEE EDAQPIRFSPPGSPSMVVHRRVPSAATTPPLPSHLTAEETPLFLAEPALPKGLPPPLQQQ QQPPPQQKSLMDQLQGVVSNFSTAIPDFHAVLAGPGGPGNGLRSLYPPPPPPQHLQMLPL QLSTFGEELVSPPADDDDDSERFKLLQEYVYEHEREGNTEEDELEEEEEDLQAASKLTPD DSPALTPPSPFRDSVASGSSVPSSPVSESVLCTPPNVSYASVILRDYKQSSSTL |
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Function |
Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling activates a phosphatidylinositol-calcium second messenger system. May participate in the central action of glutamate in the CNS, such as long-term potentiation in the hippocampus and long-term depression in the cerebellum. G-protein coupled receptor for glutamate.
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KEGG Pathway |
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Reactome Pathway | |||||
Molecular Interaction Atlas (MIA) of This DTT
Molecular Interaction Atlas (MIA) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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4 Discontinued Drug(s) Targeting This DTT
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2 Preclinical Drug(s) Targeting This DTT
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84 Investigative Drug(s) Targeting This DTT
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Molecular Expression Atlas (MEA) of This DTT
References
1 | Comparison of the mGluR1 antagonist A-841720 in rat models of pain and cognition. Behav Pharmacol. 2007 Jul;18(4):273-81. | ||||
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2 | Pfizer. Product Development Pipeline. March 31 2009. | ||||
3 | Clinical pipeline report, company report or official report of AstraZeneca (2009). | ||||
4 | Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26. | ||||
5 | Positive and negative modulation of group I metabotropic glutamate receptors. J Med Chem. 2008 Feb 14;51(3):634-47. | ||||
6 | Anticonvulsant actions of LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid). Eur J Pharmacol. 1999 Feb 26;368(1):17-24. | ||||
7 | [3H]R214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists. Mol Pharmacol. 2003 May;63(5):1082-93. | ||||
8 | Characterization of [(3)H]Quisqualate binding to recombinant rat metabotropic glutamate 1a and 5a receptors and to rat and human brain sections. J Neurochem. 2000 Dec;75(6):2590-601. | ||||
9 | Synergism of virtual screening and medicinal chemistry: identification and optimization of allosteric antagonists of metabotropic glutamate recepto... Bioorg Med Chem. 2009 Aug 1;17(15):5708-15. | ||||
10 | Biochemical and electrophysiological studies on (S)-(+)-2-(3'-carboxybicyclo(1.1.1)pentyl)-glycine (CBPG), a novel mGlu5 receptor agonist endowed with mGlu1 receptor antagonist activity. Neuropharmacology. 1999 Jul;38(7):917-26. | ||||
11 | Synthesis and biological evaluation of 2-(3'-(1H-tetrazol-5-yl) bicyclo[1.1.1]pent-1-yl)glycine (S-TBPG), a novel mGlu1 receptor antagonist. Bioorg Med Chem. 2001 Feb;9(2):221-7. | ||||
12 | Carbamoyloximes as novel non-competitive mGlu5 receptor antagonists. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4371-5. | ||||
13 | Synthesis and pharmacological characterisation of 2,4-dicarboxy-pyrroles as selective non-competitive mGluR1 antagonists. Bioorg Med Chem. 2003 Jan 17;11(2):171-83. | ||||
14 | The novel and systemically active metabotropic glutamate 1 (mGlu1) receptor antagonist 3-MATIDA reduces post-ischemic neuronal death. Neuropharmacology. 2002 May;42(6):741-51. | ||||
15 | In vitro and in vivo SAR of pyrido[3,4-d]pyramid-4-ylamine based mGluR1 antagonists. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2190-4. | ||||
16 | Discovery and SAR of 6-substituted-4-anilinoquinazolines as non-competitive antagonists of mGlu5. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6623-6. | ||||
17 | Structure-activity relationship of triazafluorenone derivatives as potent and selective mGluR1 antagonists. J Med Chem. 2005 Nov 17;48(23):7374-88. | ||||
18 | BAY36-7620: a potent non-competitive mGlu1 receptor antagonist with inverse agonist activity. Mol Pharmacol. 2001 May;59(5):965-73. | ||||
19 | Identification of a novel transmembrane domain involved in the negative modulation of mGluR1 using a newly discovered allosteric mGluR1 antagonist, 3-cyclohexyl-5-fluoro-6-methyl-7-(2-morpholin-4-ylethoxy)-4H-chromen-4-one. Neuropharmacology. 2009 Sep;57(4):438-45. | ||||
20 | Unique antipsychotic activities of the selective metabotropic glutamate receptor 1 allosteric antagonist 2-cyclopropyl-5-[1-(2-fluoro-3-pyridinyl)-5-methyl-1H-1,2,3-triazol-4-yl]-2,3-dihydro-1H-isoindol-1-one. J Pharmacol Exp Ther. 2009 Jul;330(1):179-90. | ||||
21 | Synthesis and evaluation of 6-[1-(2-[(18)F]fluoro-3-pyridyl)-5-methyl-1H-1,2,3-triazol-4-yl]quinoline for positron emission tomography imaging of the metabotropic glutamate receptor type 1 in brain. Bioorg Med Chem. 2011 Jan 1;19(1):102-10. | ||||
22 | Pharmacological characterization of a new, orally active and potent allosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fluoropyridin-... J Pharmacol Exp Ther. 2007 Jun;321(3):1144-53. | ||||
23 | A positron emission tomography radioligand for the in vivo labeling of metabotropic glutamate 1 receptor: (3-ethyl-2-[11C]methyl-6-quinolinyl)(cis- 4-methoxycyclohexyl)methanone. J Med Chem. 2005 Aug11;48(16):5096-9. | ||||
24 | Inhibition of group I metabotropic glutamate receptor responses in vivo in rats by a new generation of carboxyphenylglycine-like amino acid antagon... Neurosci Lett. 2002 Sep 20;330(2):127-30. | ||||
25 | 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: 289). | ||||
26 | Synthesis, characterization, and monkey PET studies of [ ]MK-1312, a PET tracer for quantification of mGluR1 receptor occupancy by MK-5435. Synapse. 2011 Feb;65(2):125-35. | ||||
27 | Structure-activity relationships of novel non-competitive mGluR1 antagonists: a potential treatment for chronic pain. Bioorg Med Chem Lett. 2007 Jan 15;17(2):486-90. | ||||
28 | 9H-Xanthene-9-carboxylic acid [1,2,4]oxadiazol-3-yl- and (2H-tetrazol-5-yl)-amides as potent, orally available mGlu1 receptor enhancers. Bioorg Med Chem Lett. 2005 Oct 15;15(20):4628-31. | ||||
29 | From pyrroles to 1-oxo-2,3,4,9-tetrahydro-1H-beta-carbolines: a new class of orally bioavailable mGluR1 antagonists. Bioorg Med Chem Lett. 2007 Apr 15;17(8):2254-9. | ||||
30 | Rapid hit to lead evaluation of pyrazolo[3,4-d]pyrimidin-4-one as selective and orally bioavailable mGluR1 antagonists. Bioorg Med Chem Lett. 2007 Aug 1;17(15):4303-7. | ||||
31 | Discovery of orally efficacious tetracyclic metabotropic glutamate receptor 1 (mGluR1) antagonists for the treatment of chronic pain. J Med Chem. 2007 Nov 15;50(23):5550-3. | ||||
32 | Tricyclic thienopyridine-pyrimidones/thienopyrimidine-pyrimidones as orally efficacious mGluR1 antagonists for neuropathic pain. Bioorg Med Chem Lett. 2009 Jun 15;19(12):3199-203. | ||||
33 | A-ring modifications on the triazafluorenone core structure and their mGluR1 antagonist properties. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2474-7. | ||||
34 | Fused tricyclic mGluR1 antagonists for the treatment of neuropathic pain. Bioorg Med Chem Lett. 2012 Feb 15;22(4):1575-8. | ||||
35 | Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7223-6. | ||||
36 | Positive allosteric modulators of metabotropic glutamate 1 receptor: characterization, mechanism of action, and binding site. Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):13402-7. | ||||
37 | Fluorinated 9H-xanthene-9-carboxylic acid oxazol-2-yl-amides as potent, orally available mGlu1 receptor enhancers. Bioorg Med Chem Lett. 2009 Mar 15;19(6):1666-9. | ||||
38 | Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4): Part I. Discovery of pyrazolo[3,4-d]pyrimidines as novel ... Bioorg Med Chem Lett. 2008 Oct 15;18(20):5626-30. | ||||
39 | N-Acyl-N'-arylpiperazines as negative allosteric modulators of mGlu1: identification of VU0469650, a potent and selective tool compound with CNS exposure in rats. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3713-8. | ||||
40 | Neuroprotective effects of the selective type 1 metabotropic glutamate receptor antagonist YM-202074 in rat stroke models. Brain Res. 2008 Jan 29;1191:168-79. | ||||
41 | Radioligand binding properties and pharmacological characterization of 6-amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-a]benzimidazole-2-carboxamide ... J Pharmacol Exp Ther. 2005 Oct;315(1):163-9. | ||||
42 | Synthesis, in vitro and in vivo evaluation of [11C]MMTP: a potential PET ligand for mGluR1 receptors. Bioorg Med Chem Lett. 2010 Jun 15;20(12):3499-501. | ||||
43 | Radiosynthesis and preliminary evaluation of 4-[18F]fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide as a new positron emission tomography ligand for metabotropic glutamate receptor subtype 1. Bioorg Med Chem Lett. 2011 May 15;21(10):2998-3001. | ||||
44 | Characterization of 1-(2-[18F] fluoro-3-pyridyl)-4-(2-isopropyl-1-oxo- isoindoline-5-yl)-5-methyl-1H-1,2,3-triazole, a PET ligand for imaging the metabotropic glutamate receptor type 1 in rat and monkey brains. J Neurochem. 2012 Apr;121(1):115-24. | ||||
45 | Mutational analysis and molecular modeling of the allosteric binding site of a novel, selective, noncompetitive antagonist of the metabotropic glut... J Biol Chem. 2003 Mar 7;278(10):8340-7. | ||||