Target Information
Target General Infomation | |||||
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Target ID |
T02719
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Former ID |
TTDC00126
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Target Name |
Metabotropic glutamate receptor3
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Gene Name |
GRM3
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Synonyms |
Group III metabotropic glutamate receptor; mGLUR3; GRM3
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Target Type |
Clinical Trial
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Disease | Anxiety disorder [ICD9: 300, 311; ICD10: F32, F40-F42] | ||||
Alzheimer disease; Major depressive disorder [ICD9:331, 296.2, 296.3, 710.0; ICD10: G30, F32, F33, M32] | |||||
Mood disorder [ICD10: F30-F39] | |||||
Major depressive disorder [ICD9: 296.2, 296.3, 710.0; ICD10: F32, F33, M32] | |||||
Schizophrenia [ICD9: 295; ICD10: F20] | |||||
Function |
G-protein coupled receptor for glutamate. 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 inhibits adenylate cyclase activity.
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BioChemical Class |
GPCR glutamate
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Target Validation |
T02719
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UniProt ID | |||||
Sequence |
MKMLTRLQVLTLALFSKGFLLSLGDHNFLRREIKIEGDLVLGGLFPINEKGTGTEECGRI
NEDRGIQRLEAMLFAIDEINKDDYLLPGVKLGVHILDTCSRDTYALEQSLEFVRASLTKV DEAEYMCPDGSYAIQENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSD KSRYDYFARTVPPDFYQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLRNIC IATAEKVGRSNIRKSYDSVIRELLQKPNARVVVLFMRSDDSRELIAAASRANASFTWVAS DGWGAQESIIKGSEHVAYGAITLELASQPVRQFDRYFQSLNPYNNHRNPWFRDFWEQKFQ CSLQNKRNHRRVCDKHLAIDSSNYEQESKIMFVVNAVYAMAHALHKMQRTLCPNTTKLCD AMKILDGKKLYKDYLLKINFTAPFNPNKDADSIVKFDTFGDGMGRYNVFNFQNVGGKYSY LKVGHWAETLSLDVNSIHWSRNSVPTSQCSDPCAPNEMKNMQPGDVCCWICIPCEPYEYL ADEFTCMDCGSGQWPTADLTGCYDLPEDYIRWEDAWAIGPVTIACLGFMCTCMVVTVFIK HNNTPLVKASGRELCYILLFGVGLSYCMTFFFIAKPSPVICALRRLGLGSSFAICYSALL TKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILEAPGTRRYTLA EKRETVILKCNVKDSSMLISLTYDVILVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCI IWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVVLGCLFAPKVHIILFQPQKNVVTHRLH LNRFSVSGTGTTYSQSSASTYVPTVCNGREVLDSTTSSL |
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Drugs and Mode of Action | |||||
Drug(s) | BCI-632 | Drug Info | Phase 1 | Alzheimer disease; Major depressive disorder | [523828] |
Pomaglumetad | Drug Info | Phase 1 | Schizophrenia | [523714] | |
LY-544344 | Drug Info | Discontinued in Phase 3 | Anxiety disorder | [547724] | |
LY354740 | Drug Info | Discontinued in Phase 2 | Anxiety disorder | [538869], [546477] | |
R-1578 | Drug Info | Discontinued in Phase 2 | Mood disorder | [549263] | |
RO-4995819 | Drug Info | Discontinued in Phase 2 | Major depressive disorder | [524135] | |
BCI-838 | Drug Info | Discontinued in Phase 1 | Alzheimer disease; Major depressive disorder | [523820] | |
Antagonist | (+)-MCPG | Drug Info | [525619] | ||
eGlu | Drug Info | [525820] | |||
MGS0039 | Drug Info | [527175] | |||
R-1578 | Drug Info | [551608] | |||
Agonist | (1S,3R)-ACPD | Drug Info | [525619] | ||
L-CCG-I | Drug Info | [525619] | |||
LY-544344 | Drug Info | [536166] | |||
LY354740 | Drug Info | [536959], [537037], [537272] | |||
NAAG | Drug Info | [525820] | |||
[3H]LY341495 | Drug Info | [525820] | |||
Modulator | BCI-632 | Drug Info | [1572591] | ||
BCI-838 | Drug Info | [551197] | |||
Pomaglumetad | Drug Info | [530986] | |||
RO-4995819 | Drug Info | [544330] | |||
Modulator (allosteric modulator) | compound 2 | Drug Info | [531276] | ||
compound 3 | Drug Info | [531276] | |||
compound 4 | Drug Info | [531276] | |||
MNI-135 | Drug Info | [528775] | |||
MNI-136 | Drug Info | [528775] | |||
MNI-137 | Drug Info | [528775] | |||
Ro4491533 | Drug Info | [531231] | |||
VU0463597 | Drug Info | [531911] | |||
Inhibitor | LY-379268 | Drug Info | [528620] | ||
LY-389795 | Drug Info | [528620] | |||
QUISQUALATE | Drug Info | [534590] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Neuroactive ligand-receptor interaction | ||||
Glutamatergic synapse | |||||
Cocaine addiction | |||||
PANTHER Pathway | Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | ||||
Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway | |||||
Ionotropic glutamate receptor pathway | |||||
Metabotropic glutamate receptor group II pathway | |||||
Reactome | G alpha (i) signalling events | ||||
Class C/3 (Metabotropic glutamate/pheromone receptors) | |||||
WikiPathways | GPCRs, Class C Metabotropic glutamate, pheromone | ||||
GPCR ligand binding | |||||
GPCR downstream signaling | |||||
References | |||||
Ref 523714 | ClinicalTrials.gov (NCT01487083) A Long-Term Study in Schizophrenia. U.S. National Institutes of Health. | ||||
Ref 523820 | ClinicalTrials.gov (NCT01546051) A Study of BCI-838 and Several BCI-632 Prodrugs in Healthy Volunteers. U.S. National Institutes of Health. | ||||
Ref 523828 | ClinicalTrials.gov (NCT01548703) A Multiple Ascending Dose Study of BCI-838 in Healthy Volunteers. U.S. National Institutes of Health. | ||||
Ref 524135 | ClinicalTrials.gov (NCT01733654) Investigate Efficacy & Safety of RO4995819 vs. Placebo as Adjunct Tx in Patients w/Major Depressive Disorder. U.S. National Institutes of Health. | ||||
Ref 538869 | (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: 1393). | ||||
Ref 546477 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008428) | ||||
Ref 525619 | [3H]-LY341495 as a novel antagonist radioligand for group II metabotropic glutamate (mGlu) receptors: characterization of binding to membranes of mGlu receptor subtype expressing cells. Neuropharmacology. 1999 Oct;38(10):1519-29. | ||||
Ref 525820 | Characterization of [(3)H]-LY354740 binding to rat mGlu2 and mGlu3 receptors expressed in CHO cells using semliki forest virus vectors. Neuropharmacology. 2000 Jul 24;39(10):1700-6. | ||||
Ref 527175 | Synthesis, in vitro pharmacology, structure-activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists. J Med Chem. 2004 Aug 26;47(18):4570-87. | ||||
Ref 528620 | J Med Chem. 2007 Jan 25;50(2):233-40.Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of (-)-4-amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate: identification of potent, selective, and orally bioavailable agonists for mGlu2/3 receptors. | ||||
Ref 528775 | A novel family of potent negative allosteric modulators of group II metabotropic glutamate receptors. J Pharmacol Exp Ther. 2007 Jul;322(1):254-64. Epub 2007 Apr 6. | ||||
Ref 530986 | LY-2140023, a prodrug of the group II metabotropic glutamate receptor agonist LY-404039 for the potential treatment of schizophrenia. Curr Opin Investig Drugs. 2010 Jul;11(7):833-45. | ||||
Ref 531231 | Synthesis and characterization of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives: Part 4. In vivo active potent and selective non-competitive metabotropic glutamate receptor 2/3 antagonists. Bioorg Med Chem Lett. 2010 Dec 1;20(23):6969-74. | ||||
Ref 531276 | Chemical switch of a metabotropic glutamate receptor 2 silent allosteric modulator into dual metabotropic glutamate receptor 2/3 negative/positive allosteric modulators. J Med Chem. 2010 Dec 23;53(24):8775-9. | ||||
Ref 531911 | Development of a novel, CNS-penetrant, metabotropic glutamate receptor 3 (mGlu3) NAM probe (ML289) derived from a closely related mGlu5 PAM. Bioorg Med Chem Lett. 2012 Jun 15;22(12):3921-5. | ||||
Ref 534590 | J Med Chem. 1998 Mar 12;41(6):930-9.Excitatory amino acid receptor ligands: resolution, absolute stereochemistry, and enantiopharmacology of 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid. | ||||
Ref 536959 | Modulation of group II metabotropic glutamate receptor (mGlu2) elicits common changes in rat and mice sleep-wake architecture. Eur J Pharmacol. 2009 Jan 28;603(1-3):62-72. Epub 2008 Nov 17. | ||||
Ref 536982 | Glutamate receptor mGlu2 and mGlu3 knockout striata are dopamine supersensitive, with elevated D2(High) receptors and marked supersensitivity to the dopamine agonist (+)PHNO. Synapse. 2009 Mar;63(3):247-51. | ||||
Ref 537037 | Effects of a metabotropic glutamate receptor group II agonist LY354740 in animal models of positive schizophrenia symptoms and cognition. Behav Pharmacol. 2009 Feb;20(1):56-66. | ||||
Ref 537133 | Glutamate and dopamine components in schizophrenia. J Psychiatry Neurosci. 2009 Mar;34(2):143-9. | ||||
Ref 537272 | Mutagenesis and molecular modeling of the orthosteric binding site of the mGlu2 receptor determining interactions of the group II receptor antagonist (3)H-HYDIA. ChemMedChem. 2009 Jul;4(7):1086-94. | ||||
Ref 537518 | Positive allosteric modulators of the metabotropic glutamate receptor 2 for the treatment of schizophrenia. Expert Opin Ther Pat. 2009 Jun 24. | ||||
Ref 544330 | Novel glutamatergic drugs for the treatment of mood disorders. Neuropsychiatr Dis Treat. 2013; 9: 1101-1112. |
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