Target Information
Target General Infomation | |||||
---|---|---|---|---|---|
Target ID |
T02719
|
||||
Former ID |
TTDC00126
|
||||
Target Name |
Metabotropic glutamate receptor3
|
||||
Gene Name |
GRM3
|
||||
Synonyms |
Group III metabotropic glutamate receptor; mGLUR3; GRM3
|
||||
Target Type |
Clinical Trial
|
||||
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.
|
||||
BioChemical Class |
GPCR glutamate
|
||||
Target Validation |
T02719
|
||||
UniProt ID | |||||
Sequence |
MKMLTRLQVLTLALFSKGFLLSLGDHNFLRREIKIEGDLVLGGLFPINEKGTGTEECGRI
NEDRGIQRLEAMLFAIDEINKDDYLLPGVKLGVHILDTCSRDTYALEQSLEFVRASLTKV DEAEYMCPDGSYAIQENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSD KSRYDYFARTVPPDFYQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLRNIC IATAEKVGRSNIRKSYDSVIRELLQKPNARVVVLFMRSDDSRELIAAASRANASFTWVAS DGWGAQESIIKGSEHVAYGAITLELASQPVRQFDRYFQSLNPYNNHRNPWFRDFWEQKFQ CSLQNKRNHRRVCDKHLAIDSSNYEQESKIMFVVNAVYAMAHALHKMQRTLCPNTTKLCD AMKILDGKKLYKDYLLKINFTAPFNPNKDADSIVKFDTFGDGMGRYNVFNFQNVGGKYSY LKVGHWAETLSLDVNSIHWSRNSVPTSQCSDPCAPNEMKNMQPGDVCCWICIPCEPYEYL ADEFTCMDCGSGQWPTADLTGCYDLPEDYIRWEDAWAIGPVTIACLGFMCTCMVVTVFIK HNNTPLVKASGRELCYILLFGVGLSYCMTFFFIAKPSPVICALRRLGLGSSFAICYSALL TKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILEAPGTRRYTLA EKRETVILKCNVKDSSMLISLTYDVILVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCI IWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVVLGCLFAPKVHIILFQPQKNVVTHRLH LNRFSVSGTGTTYSQSSASTYVPTVCNGREVLDSTTSSL |
||||
Drugs and Mode of Action | |||||
Drug(s) | BCI-632 | Drug Info | Phase 1 | Alzheimer disease; Major depressive disorder | [1] |
Pomaglumetad | Drug Info | Phase 1 | Schizophrenia | [2] | |
LY-544344 | Drug Info | Discontinued in Phase 3 | Anxiety disorder | [3] | |
LY354740 | Drug Info | Discontinued in Phase 2 | Anxiety disorder | [4], [5] | |
R-1578 | Drug Info | Discontinued in Phase 2 | Mood disorder | [6] | |
RO-4995819 | Drug Info | Discontinued in Phase 2 | Major depressive disorder | [7] | |
BCI-838 | Drug Info | Discontinued in Phase 1 | Alzheimer disease; Major depressive disorder | [8] | |
Antagonist | (+)-MCPG | Drug Info | [9] | ||
eGlu | Drug Info | [10] | |||
MGS0039 | Drug Info | [11] | |||
R-1578 | Drug Info | [12] | |||
Agonist | (1S,3R)-ACPD | Drug Info | [9] | ||
L-CCG-I | Drug Info | [9] | |||
LY-544344 | Drug Info | [13] | |||
LY354740 | Drug Info | [14], [15], [16] | |||
NAAG | Drug Info | [10] | |||
[3H]LY341495 | Drug Info | [10] | |||
Modulator | BCI-632 | Drug Info | [17] | ||
BCI-838 | Drug Info | [18] | |||
Pomaglumetad | Drug Info | [19] | |||
RO-4995819 | Drug Info | [20] | |||
Modulator (allosteric modulator) | compound 2 | Drug Info | [21] | ||
compound 3 | Drug Info | [21] | |||
compound 4 | Drug Info | [21] | |||
MNI-135 | Drug Info | [22] | |||
MNI-136 | Drug Info | [22] | |||
MNI-137 | Drug Info | [22] | |||
Ro4491533 | Drug Info | [23] | |||
VU0463597 | Drug Info | [24] | |||
Inhibitor | LY-379268 | Drug Info | [25] | ||
LY-389795 | Drug Info | [25] | |||
QUISQUALATE | Drug Info | [26] | |||
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 1 | ClinicalTrials.gov (NCT01548703) A Multiple Ascending Dose Study of BCI-838 in Healthy Volunteers. U.S. National Institutes of Health. | ||||
REF 2 | ClinicalTrials.gov (NCT01487083) A Long-Term Study in Schizophrenia. U.S. National Institutes of Health. | ||||
REF 3 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018821) | ||||
REF 4 | (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 5 | 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 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034342) | ||||
REF 7 | 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 8 | ClinicalTrials.gov (NCT01546051) A Study of BCI-838 and Several BCI-632 Prodrugs in Healthy Volunteers. U.S. National Institutes of Health. | ||||
REF 9 | [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 10 | 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 11 | 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 12 | Clinical pipeline report, company report or official report of Roche. | ||||
REF 13 | Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17. | ||||
REF 14 | 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 15 | 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 16 | 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 17 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | ||||
REF 18 | Metabotropic glutamate receptor subtype 2 (GRM2; MGLUR2); GRM3 (MGLUR3). SciBX 3(13); doi:10.1038/scibx.2010.413. April 1 2010 | ||||
REF 19 | 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 20 | Novel glutamatergic drugs for the treatment of mood disorders. Neuropsychiatr Dis Treat. 2013; 9: 1101-1112. | ||||
REF 21 | 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 22 | 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 23 | 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 24 | 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 25 | 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 26 | 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. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.