Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T62820
(Former ID: TTDR00321)
|
|||||
| Target Name |
Metabotropic glutamate receptor 2 (mGluR2)
|
|||||
| Synonyms |
mGLUR2; Group II metabotropic glutamate receptor; Glutamate receptor mGLU2; GPRC1B
Click to Show/Hide
|
|||||
| Gene Name |
GRM2
|
|||||
| Target Type |
Clinical trial target
|
[1] | ||||
| Disease | [+] 9 Target-related Diseases | + | ||||
| 1 | Alzheimer disease [ICD-11: 8A20] | |||||
| 2 | Dengue fever [ICD-11: 1D2Z] | |||||
| 3 | Obesity [ICD-11: 5B80-5B81] | |||||
| 4 | Psychotic disorder [ICD-11: 6A20-6A25] | |||||
| 5 | Bipolar disorder [ICD-11: 6A60] | |||||
| 6 | Depression [ICD-11: 6A70-6A7Z] | |||||
| 7 | Epilepsy/seizure [ICD-11: 8A61-8A6Z] | |||||
| 8 | Mental/behavioural/neurodevelopmental disorder [ICD-11: 6E20-6E8Z] | |||||
| 9 | Schizophrenia [ICD-11: 6A20] | |||||
| 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, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. May mediate suppression of neurotransmission or may be involved in synaptogenesis or synaptic stabilization. G-protein coupled receptor for glutamate.
Click to Show/Hide
|
|||||
| BioChemical Class |
GPCR glutamate
|
|||||
| UniProt ID | ||||||
| Sequence |
MGSLLALLALLLLWGAVAEGPAKKVLTLEGDLVLGGLFPVHQKGGPAEDCGPVNEHRGIQ
RLEAMLFALDRINRDPHLLPGVRLGAHILDSCSKDTHALEQALDFVRASLSRGADGSRHI CPDGSYATHGDAPTAITGVIGGSYSDVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDY FARTVPPDFFQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFELEARARNICVATSEK VGRAMSRAAFEGVVRALLQKPSARVAVLFTRSEDARELLAASQRLNASFTWVASDGWGAL ESVVAGSEGAAEGAITIELASYPISDFASYFQSLDPWNNSRNPWFREFWEQRFRCSFRQR DCAAHSLRAVPFEQESKIMFVVNAVYAMAHALHNMHRALCPNTTRLCDAMRPVNGRRLYK DFVLNVKFDAPFRPADTHNEVRFDRFGDGIGRYNIFTYLRAGSGRYRYQKVGYWAEGLTL DTSLIPWASPSAGPLPASRCSEPCLQNEVKSVQPGEVCCWLCIPCQPYEYRLDEFTCADC GLGYWPNASLTGCFELPQEYIRWGDAWAVGPVTIACLGALATLFVLGVFVRHNATPVVKA SGRELCYILLGGVFLCYCMTFIFIAKPSTAVCTLRRLGLGTAFSVCYSALLTKTNRIARI FGGAREGAQRPRFISPASQVAICLALISGQLLIVVAWLVVEAPGTGKETAPERREVVTLR CNHRDASMLGSLAYNVLLIALCTLYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIF YVTSSDYRVQTTTMCVSVSLSGSVVLGCLFAPKLHIILFQPQKNVVSHRAPTSRFGSAAA RASSSLGQGSGSQFVPTVCNGREVVDSTTSSL Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 10 Clinical Trial Drugs | + | ||||
| 1 | JNJ-64281802 | Drug Info | Phase 2 | Dengue | [2] | |
| 2 | MP-101 | Drug Info | Phase 2 | Alzheimer disease | [3] | |
| 3 | Oleoyl-estrone | Drug Info | Phase 2 | Obesity | [4] | |
| 4 | RO-4995819 | Drug Info | Phase 2 | Major depressive disorder | [5] | |
| 5 | ADX71149 | Drug Info | Phase 1 | Epilepsy | [6] | |
| 6 | BCI-632 | Drug Info | Phase 1 | Major depressive disorder | [7] | |
| 7 | BCI-838 | Drug Info | Phase 1 | Major depressive disorder | [8] | |
| 8 | JNJ-42491293 | Drug Info | Phase 1 | Psychiatric disorder | [9] | |
| 9 | LY-2979165 | Drug Info | Phase 1 | Bipolar disorder | [10] | |
| 10 | Pomaglumetad | Drug Info | Phase 1 | Schizophrenia | [11] | |
| Discontinued Drug(s) | [+] 6 Discontinued Drugs | + | ||||
| 1 | LY-544344 | Drug Info | Discontinued in Phase 3 | Anxiety disorder | [12] | |
| 2 | LY-2300559 | Drug Info | Discontinued in Phase 2 | Migraine | [13] | |
| 3 | LY354740 | Drug Info | Discontinued in Phase 2 | Anxiety disorder | [14], [15] | |
| 4 | R-1578 | Drug Info | Discontinued in Phase 2 | Mood disorder | [16] | |
| 5 | RG1578 | Drug Info | Discontinued in Phase 2 | Major depressive disorder | [16] | |
| 6 | TS-032 | Drug Info | Discontinued in Phase 1 | Schizophrenia | [17] | |
| Mode of Action | [+] 6 Modes of Action | + | ||||
| Modulator | [+] 9 Modulator drugs | + | ||||
| 1 | JNJ-64281802 | Drug Info | [18] | |||
| 2 | RO-4995819 | Drug Info | [20] | |||
| 3 | ADX71149 | Drug Info | [21] | |||
| 4 | BCI-838 | Drug Info | [23] | |||
| 5 | LY-2979165 | Drug Info | [25] | |||
| 6 | Pomaglumetad | Drug Info | [1] | |||
| 7 | LY-2300559 | Drug Info | [28] | |||
| 8 | RG1578 | Drug Info | [31] | |||
| 9 | DT-2228 | Drug Info | [40] | |||
| Agonist | [+] 11 Agonist drugs | + | ||||
| 1 | MP-101 | Drug Info | [3] | |||
| 2 | Oleoyl-estrone | Drug Info | [6], [19] | |||
| 3 | LY-544344 | Drug Info | [27] | |||
| 4 | LY354740 | Drug Info | [29] | |||
| 5 | TS-032 | Drug Info | [32] | |||
| 6 | (1S,3R)-ACPD | Drug Info | [34] | |||
| 7 | (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate | Drug Info | [35], [36] | |||
| 8 | (S)-4C3HPG | Drug Info | [33] | |||
| 9 | DCG IV | Drug Info | [36] | |||
| 10 | L-CCG-I | Drug Info | [34] | |||
| 11 | MGS0028 | Drug Info | [44] | |||
| Antagonist | [+] 56 Antagonist drugs | + | ||||
| 1 | BCI-632 | Drug Info | [22] | |||
| 2 | Ethinyl-pyrazole derivative 1 | Drug Info | [26] | |||
| 3 | Ethinyl-pyrazole derivative 2 | Drug Info | [26] | |||
| 4 | Ethinyl-pyrazole derivative 3 | Drug Info | [26] | |||
| 5 | Heteroaryl-pyrazole derivative 1 | Drug Info | [26] | |||
| 6 | Heteroaryl-pyrazole derivative 2 | Drug Info | [26] | |||
| 7 | Heteroaryl-pyrazole derivative 3 | Drug Info | [26] | |||
| 8 | N-substituted pyrazole derivative 1 | Drug Info | [26] | |||
| 9 | N-substituted pyrazole derivative 2 | Drug Info | [26] | |||
| 10 | N-substituted pyrazole derivative 3 | Drug Info | [26] | |||
| 11 | PMID25435285-Compound-10 | Drug Info | [26] | |||
| 12 | PMID25435285-Compound-15 | Drug Info | [26] | |||
| 13 | PMID25435285-Compound-16 | Drug Info | [26] | |||
| 14 | PMID25435285-Compound-20 | Drug Info | [26] | |||
| 15 | PMID25435285-Compound-22 | Drug Info | [26] | |||
| 16 | PMID25435285-Compound-25 | Drug Info | [26] | |||
| 17 | PMID25435285-Compound-26 | Drug Info | [26] | |||
| 18 | PMID25435285-Compound-37 | Drug Info | [26] | |||
| 19 | PMID25435285-Compound-38 | Drug Info | [26] | |||
| 20 | PMID25435285-Compound-39 | Drug Info | [26] | |||
| 21 | PMID25435285-Compound-40 | Drug Info | [26] | |||
| 22 | PMID25435285-Compound-41 | Drug Info | [26] | |||
| 23 | PMID25435285-Compound-42 | Drug Info | [26] | |||
| 24 | PMID25435285-Compound-43 | Drug Info | [26] | |||
| 25 | PMID25435285-Compound-44 | Drug Info | [26] | |||
| 26 | PMID25435285-Compound-45 | Drug Info | [26] | |||
| 27 | PMID25435285-Compound-46 | Drug Info | [26] | |||
| 28 | PMID25435285-Compound-47 | Drug Info | [26] | |||
| 29 | PMID25435285-Compound-49 | Drug Info | [26] | |||
| 30 | PMID25435285-Compound-50 | Drug Info | [26] | |||
| 31 | PMID25435285-Compound-51 | Drug Info | [26] | |||
| 32 | PMID25435285-Compound-52 | Drug Info | [26] | |||
| 33 | PMID25435285-Compound-53 | Drug Info | [26] | |||
| 34 | Pyrazole derivative 76 | Drug Info | [26] | |||
| 35 | Pyrazole derivative 77 | Drug Info | [26] | |||
| 36 | Pyrazole derivative 78 | Drug Info | [26] | |||
| 37 | Pyrazole derivative 79 | Drug Info | [26] | |||
| 38 | Quinoline derivative 3 | Drug Info | [26] | |||
| 39 | Quinoline derivative 4 | Drug Info | [26] | |||
| 40 | Quinoline derivative 5 | Drug Info | [26] | |||
| 41 | Quinoline derivative 6 | Drug Info | [26] | |||
| 42 | Quinoline derivative 7 | Drug Info | [26] | |||
| 43 | Quinoline derivative 8 | Drug Info | [26] | |||
| 44 | Quinoline derivative 9 | Drug Info | [26] | |||
| 45 | Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 1 | Drug Info | [26] | |||
| 46 | Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 2 | Drug Info | [26] | |||
| 47 | Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 3 | Drug Info | [26] | |||
| 48 | Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 4 | Drug Info | [26] | |||
| 49 | Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 5 | Drug Info | [26] | |||
| 50 | Tetra-hydro-imidazo[1,5-d][1,4]oxazepin-3-yl derivative 6 | Drug Info | [26] | |||
| 51 | R-1578 | Drug Info | [30] | |||
| 52 | (+)-MCPG | Drug Info | [33] | |||
| 53 | alpha-methylserine-O-phosphate | Drug Info | [33] | |||
| 54 | eGlu | Drug Info | [29] | |||
| 55 | PCCG-4 | Drug Info | [46] | |||
| 56 | [3H]LY341495 | Drug Info | [34], [35] | |||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | JNJ-42491293 | Drug Info | [24] | |||
| Modulator (allosteric modulator) | [+] 22 Modulator (allosteric modulator) drugs | + | ||||
| 1 | 3-MPPTS | Drug Info | [37] | |||
| 2 | 4-APPES | Drug Info | [37] | |||
| 3 | 4-MPPTS | Drug Info | [38] | |||
| 4 | biphenylindanone A | Drug Info | [39] | |||
| 5 | CBiPES | Drug Info | [37] | |||
| 6 | cyPPTS | Drug Info | [37] | |||
| 7 | GSK1331268 | Drug Info | [41] | |||
| 8 | JNJ-42153605 | Drug Info | [42] | |||
| 9 | MNI-135 | Drug Info | [45] | |||
| 10 | MNI-136 | Drug Info | [45] | |||
| 11 | MNI-137 | Drug Info | [45] | |||
| 12 | PMID20409708C34 | Drug Info | [47] | |||
| 13 | PMID21155570C14 | Drug Info | [48] | |||
| 14 | PMID22364337C48 | Drug Info | [49] | |||
| 15 | PTBE | Drug Info | [50] | |||
| 16 | Ro4491533 | Drug Info | [51] | |||
| 17 | RO4988546 | Drug Info | [52] | |||
| 18 | RO5488608 | Drug Info | [52] | |||
| 19 | Ro64-5229 | Drug Info | [53] | |||
| 20 | THIIC | Drug Info | [54] | |||
| 21 | [3H]2,2,2-TEMPS | Drug Info | [38], [52] | |||
| 22 | [3H]JNJ-40068782 | Drug Info | [55] | |||
| Inhibitor | [+] 3 Inhibitor drugs | + | ||||
| 1 | LY-379268 | Drug Info | [43] | |||
| 2 | LY-389795 | Drug Info | [43] | |||
| 3 | [3H]quisqualate | Drug Info | [56] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: ADX71149 | Ligand Info | |||||
| Structure Description | Cryo-EM structure of Gi-bound metabotropic glutamate receptor mGlu2 | PDB:7E9G | ||||
| Method | Electron microscopy | Resolution | 3.50 Å | Mutation | Yes | [57] |
| PDB Sequence |
KKVLTLEGDL
32 VLGGLFPVHQ42 KGGPAEDCGP52 VNEHRGIQRL62 EAMLFALDRI72 NRDPHLLPGV 82 RLGAHILDSC92 SKDTHALEQA102 LDFVRASLIT137 GVIGGSYSDV147 SIQVANLLRL 157 FQIPQISYAS167 TSAKLSDKSR177 YDYFARTVPP187 DFFQAKAMAE197 ILRFFNWTYV 207 STVASEGDYG217 ETGIEAFELE227 ARARNICVAT237 SEKVGRAMSR247 AAFEGVVRAL 257 LQKPSARVAV267 LFTRSEDARE277 LLAASQRLNA287 SFTWVASDGW297 GALESVVAGS 307 EGAAEGAITI317 ELASYPISDF327 ASYFQSLDPW337 NNSRNPWFRE347 FWEQRFRCSF 357 RQRDCAAHSL367 RAVPFEQESK377 IMFVVNAVYA387 MAHALHNMHR397 ALCPNTTRLC 407 DAMRPVNGRR417 LYKDFVLNVK427 FDAPFRPADT437 HNEVRFDRFG447 DGIGRYNIFT 457 YLRAGSGRYR467 YQKVGYWAEG477 LTLDTSLIPW487 ASPSAGPLPA497 SRCSEPCLQN 507 EVKSVQPGEV517 CCWLCIPCQP527 YEYRLDEFTC537 ADCGLGYWPN547 ASLTGCFELP 557 QEYIRWGDAW567 AVGPVTIACL577 GALATLFVLG587 VFVRHNATPV597 VKAAGRELCY 607 ILLGGVFLCY617 CMTFIFIAKP627 STAVCTLRRL637 GLGTAFSVCY647 SALLTKTNRI 657 ARIFGGAREG667 AQRPRFISPA677 SQVAICLALI687 SGQLLIVVAW697 LVVEAPGTGK 707 ETAPERREVV717 TLRCNHRDAS727 MLGSLAYNVL737 LIALCTLYAF747 KTRKCPENFN 757 EAKFIGFTMY767 TTCIIWLAFL777 PIFYVTSSDY787 RVQTTTMCVS797 VSLSGSVVLG 807 CLFAPKLHI
|
|||||
|
|
||||||
| Ligand Name: [3H]LY341495 | Ligand Info | |||||
| Structure Description | CryoEM Structure of Full-Length mGlu2 in Inactive-State Bound to Antagonist LY341495 | PDB:7MTQ | ||||
| Method | Electron microscopy | Resolution | 3.65 Å | Mutation | No | [58] |
| PDB Sequence |
KVLTLEGDLV
33 LGGLFPVHQK43 PAEDCGPVNE55 HRGIQRLEAM65 LFALDRINRD75 PHLLPGVRLG 85 AHILDSCSKD95 THALEQALDF105 VRASLPTAIT137 GVIGGSYSDV147 SIQVANLLRL 157 FQIPQISYAS167 TSAKLSDKSR177 YDYFARTVPP187 DFFQAKAMAE197 ILRFFNWTYV 207 STVASEGDYG217 ETGIEAFELE227 ARARNICVAT237 SEKVGRAMSR247 AAFEGVVRAL 257 LQKPSARVAV267 LFTRSEDARE277 LLAASQRLNA287 SFTWVASDGW297 GALESVVAGS 307 EGAAEGAITI317 ELASYPISDF327 ASYFQSLDPW337 NNSRNPWFRE347 FWEQRFRCSF 357 RQRDCAAHSL367 RAVPFEQESK377 IMFVVNAVYA387 MAHALHNMHR397 ALCPNTTRLC 407 DAMRPVNGRR417 LYKDFVLNVK427 FDAPFRPADT437 HNEVRFDRFG447 DGIGRYNIFT 457 YLRAGSGRYR467 YQKVGYWAEG477 LTLDTSLIPW487 ASAGPLPASR499 CSEPCLQNEV 509 KSVQEVCCWL521 CIPCQYELDE534 FTCADCGLGW545 PNLTGCFELP557 QEYIRWDAWA 568 VGPVTIACLG578 ALATLFVLGV588 FVRHNATPVV598 KASGRELCYI608 LLGGVFLCYC 618 MTFIFIAKPS628 TAVCTLRRLG638 LGTAFSVCYS648 ALLTKTNRIA658 RSPASQVAIC 683 LALISGQLLI693 VVAWLVVEAP703 GTETAPERRE715 VVTLRCNHRD725 ASMLGSLAYN 735 VLLILCTLYA746 FKTRKCPENF756 NEAKFIGFTM766 YTTCIIWLAF776 LPIFYVTSSD 786 YRVQTTTMCV796 SVSLSGSVVL806 GCLFAPKLHI816 IL
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
|
Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Phospholipase D signaling pathway | hsa04072 | Affiliated Target |
|
| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
|
| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Glutamatergic synapse | hsa04724 | Affiliated Target |
|
| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
|---|---|---|---|---|---|
| Closeness centrality | 1.56E-01 | Radiality | 1.22E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 2.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "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 | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| 2 | Glutamatergic synapse | |||||
| 3 | Cocaine addiction | |||||
| Panther Pathway | [+] 4 Panther Pathways | + | ||||
| 1 | Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | |||||
| 2 | Heterotrimeric G-protein signaling pathway-Gq alpha and Go alpha mediated pathway | |||||
| 3 | Ionotropic glutamate receptor pathway | |||||
| 4 | Metabotropic glutamate receptor group II pathway | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | G alpha (i) signalling events | |||||
| 2 | Class C/3 (Metabotropic glutamate/pheromone receptors) | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | GPCRs, Class C Metabotropic glutamate, pheromone | |||||
| 2 | GPCR ligand binding | |||||
| 3 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | 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 2 | ClinicalTrials.gov (NCT04480736) A Phase 2a, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics of Repeated Oral Doses of JNJ-64281802 Against Dengue Serotype 1 Infection in a Dengue Human Challenge Model in Healthy Adult Participants. U.S.National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT03044249) A Study of MP-101 in Dementia-Related Psychosis and/or Agitation and Aggression. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT00449202) Phase 2a Obesity Study of Oral Doses of Oleoyl-Estrone (MP-101). U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT01457677) ARTDeCo Study: A Study of RO4995819 in Patients With Major Depressive Disorder And Inadequate Response to Ongoing Antidepressant Treatment in Hoffmann-La Roche. | |||||
| REF 6 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 7 | ClinicalTrials.gov (NCT01548703) A Multiple Ascending Dose Study of BCI-838 in Healthy Volunteers. U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT01548703) A Multiple Ascending Dose Study of BCI-838 in Healthy Volunteers in BrainCells Inc. | |||||
| REF 9 | ClinicalTrials.gov (NCT01359852) A Study of [11C]JNJ-42491293, a Possible PET Ligand for the mGlu2 Receptor, in Healthy Adult Volunteers in Healthy Volunteers in Johnson & Johnson Pharmaceutical Research & Development, L.L.C. | |||||
| REF 10 | ClinicalTrials.gov (NCT01248052) A First Human Dose Study to Investigate Safety and Tolerability of LY2979165 in Healthy Volunteers in Eli Lilly and Company. | |||||
| REF 11 | ClinicalTrials.gov (NCT01487083) A Long-Term Study in Schizophrenia. U.S. National Institutes of Health. | |||||
| REF 12 | 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 13 | ClinicalTrials.gov (NCT01184508) A Study in Migraine Prevention. U.S. National Institutes of Health. | |||||
| REF 14 | 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: 1393). | |||||
| REF 15 | 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 16 | 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 17 | ClinicalTrials.gov (NCT00876304) Multiple Dose Safety Study of PF-04802540 in Subjects With Schizophrenia. U.S. National Institutes of Health. | |||||
| REF 18 | Pharmacokinetic and pharmacodynamic characterisation of JNJ-40411813, a positive allosteric modulator of mGluR2, in two randomised, double-blind phase-I studies. J Psychopharmacol. 2015 Apr;29(4):414-25. | |||||
| REF 19 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 20 | Novel glutamatergic drugs for the treatment of mood disorders. Neuropsychiatr Dis Treat. 2013; 9: 1101-1112. | |||||
| REF 21 | MGlu2 receptor-mediated modulation of conditioned avoidance behavior in rats. European journal of pharmacology. 01/2014; 727(1). | |||||
| REF 22 | 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 23 | Metabotropic glutamate receptor subtype 2 (GRM2; MGLUR2); GRM3 (MGLUR3). SciBX 3(13); doi:10.1038/scibx.2010.413. April 1 2010 | |||||
| REF 24 | Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders. Nat Rev Drug Discov. 2014 Sep;13(9):692-708. | |||||
| REF 25 | Annual Reports in Medicinal Chemistry. Volume 47, 2012, Page(78). | |||||
| REF 26 | Novel metabotropic glutamate receptor 2/3 antagonists and their therapeutic applications: a patent review (2005 - present).Expert Opin Ther Pat. 2015 Jan;25(1):69-90. | |||||
| REF 27 | Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17. | |||||
| REF 28 | Annual Reports in Medicinal Chemistry. Elsevier (ISBN: 9780123964922). 2012, p78 | |||||
| REF 29 | 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 30 | Clinical pipeline report, company report or official report of Roche. | |||||
| REF 31 | Company report (Roche pipeline: 15 April 2014) | |||||
| REF 32 | Metabotropic glutamate receptor subtype 2/3 (mGluR2/3); serotonin receptor (5-HT2A receptor). SciBX 1(6); doi:10.1038/scibx.2008.145. March 6 2008 | |||||
| REF 33 | Characterization of [3H]-(2S,2'R,3'R)-2-(2',3'-dicarboxy-cyclopropyl)glycine ([3H]-DCG IV) binding to metabotropic mGlu2 receptor-transfected cell membranes. Br J Pharmacol. 1998 Feb;123(3):497-504. | |||||
| REF 34 | [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 35 | Group II metabotropic glutamate receptors within the amygdala regulate fear as assessed with potentiated startle in rats. Behav Neurosci. 2002 Dec;116(6):1075-83. | |||||
| REF 36 | Attenuation of seizures induced by homocysteic acid in immature rats by metabotropic glutamate group II and group III receptor agonists. Brain Res. 2001 Jul 27;908(2):120-9. | |||||
| REF 37 | Metabotropic glutamate 2 receptor potentiators: receptor modulation, frequency-dependent synaptic activity, and efficacy in preclinical anxiety and... Psychopharmacology (Berl). 2005 Apr;179(1):271-83. | |||||
| REF 38 | SAR study of a subtype selective allosteric potentiator of metabotropic glutamate 2 receptor, N-(4-phenoxyphenyl)-N-(3-pyridinylmethyl)ethanesulfonamide. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3099-102. | |||||
| REF 39 | Biphenyl-indanones: allosteric potentiators of the metabotropic glutamate subtype 2 receptor. Bioorg Med Chem Lett. 2005 Oct 1;15(19):4354-8. | |||||
| REF 40 | 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: 290). | |||||
| REF 41 | The identification of structurally novel, selective, orally bioavailable positive modulators of mGluR2. Bioorg Med Chem Lett. 2010 Jan 15;20(2):759-62. | |||||
| REF 42 | Discovery of 3-cyclopropylmethyl-7-(4-phenylpiperidin-1-yl)-8-trifluoromethyl[1,2,4]triazolo[4,3-a]pyridine (JNJ-42153605): a positive allosteric modulator of the metabotropic glutamate 2 receptor. JMed Chem. 2012 Oct 25;55(20):8770-89. | |||||
| REF 43 | Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of (-)-4-amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate: identif... J Med Chem. 2007 Jan 25;50(2):233-40. | |||||
| REF 44 | Synthesis, SARs, and pharmacological characterization of 2-amino-3 or 6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent, selective, and orally active group II metabotropic glutamate receptor agonists. J Med Chem. 2000 Dec 14;43(25):4893-909. | |||||
| REF 45 | A novel family of potent negative allosteric modulators of group II metabotropic glutamate receptors. J Pharmacol Exp Ther. 2007 Jul;322(1):254-64. | |||||
| REF 46 | Synthesis and pharmacological characterization of all sixteen stereoisomers of 2-(2'-carboxy-3'-phenylcyclopropyl)glycine. Focus on (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine, a novel and selective group II metabotropic glutamate receptors antagonist. J Med Chem. 1996 May 24;39(11):2259-69. | |||||
| REF 47 | 3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones as positive allosteric modulators of mGluR2 for the treatment of schizophrenia: Hit-to-lead efforts. Bioorg Med Chem Lett. 2010 May 15;20(10):3129-33. | |||||
| REF 48 | Design and synthesis of an orally active metabotropic glutamate receptor subtype-2 (mGluR2) positive allosteric modulator (PAM) that decreases cocaine self-administration in rats. J Med Chem. 2011 Jan 13;54(1):342-53. | |||||
| REF 49 | Discovery of 1,4-disubstituted 3-cyano-2-pyridones: a new class of positive allosteric modulators of the metabotropic glutamate 2 receptor. J Med Chem. 2012 Mar 8;55(5):2388-405. | |||||
| REF 50 | Phenyl-tetrazolyl acetophenones: discovery of positive allosteric potentiatiors for the metabotropic glutamate 2 receptor. J Med Chem. 2004 Aug 26;47(18):4595-9. | |||||
| REF 51 | Characterization of an mGluR2/3 negative allosteric modulator in rodent models of depression. J Neurogenet. 2011 Dec;25(4):152-66. | |||||
| REF 52 | Structural determinants of allosteric antagonism at metabotropic glutamate receptor 2: mechanistic studies with new potent negative allosteric modulators. Br J Pharmacol. 2011 Sep;164(2b):521-37. | |||||
| REF 53 | Synthesis of heterocyclic enol ethers and their use as group 2 metabotropic glutamate receptor antagonists. Bioorg Med Chem Lett. 1999 Aug 2;9(15):2173-6. | |||||
| REF 54 | N-(4-((2-(trifluoromethyl)-3-hydroxy-4-(isobutyryl)phenoxy)methyl)benzyl)-1-methyl-1H-imidazole-4-carboxamide (THIIC), a novel metabotropic glutamate 2 potentiator with potential anxiolytic/antidepressant properties: in vivo profiling suggests a link between behavioral and central nervous system neurochemical changes. J Pharmacol Exp Ther. 2011 Jan;336(1):165-77. | |||||
| REF 55 | Pharmacological characterization of JNJ-40068782, a new potent, selective, and systemically active positive allosteric modulator of the mGlu2 receptor and its radioligand [3H]JNJ-40068782. J Pharmacol Exp Ther. 2013 Sep;346(3):514-27. | |||||
| REF 56 | Excitatory amino acid receptor ligands: resolution, absolute stereochemistry, and enantiopharmacology of 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)... J Med Chem. 1998 Mar 12;41(6):930-9. | |||||
| REF 57 | Structures of G(i)-bound metabotropic glutamate receptors mGlu2 and mGlu4. Nature. 2021 Jun;594(7864):583-588. | |||||
| REF 58 | G-protein activation by a metabotropic glutamate receptor. Nature. 2021 Jul;595(7867):450-454. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.