mGlu<sub>5</sub> receptor | Metabotropic glutamate receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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mGlu5 receptor

Target not currently curated in GtoImmuPdb

Target id: 293

Nomenclature: mGlu5 receptor

Family: Metabotropic glutamate receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Contents:

Gene and Protein Information
class C G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 1212 11q14.2 GRM5 glutamate metabotropic receptor 5 59-60
Mouse 7 1203 7 D3 Grm5 glutamate receptor, metabotropic 5
Rat 7 1203 1q32 Grm5 glutamate metabotropic receptor 5 1,40
Previous and Unofficial Names
mGluR5 | GPRC1E | glutamate receptor
Database Links
Specialist databases
GPCRDB grm5_human (Hs), grm5_mouse (Mm), grm5_rat (Rn)
Other databases
ChEMBL Target CHEMBL3227 (Hs), CHEMBL1641352 (Mm), CHEMBL2564 (Rn)
DrugBank Target P41594 (Hs)
Ensembl Gene ENSG00000168959 (Hs), ENSMUSG00000049583 (Mm), ENSRNOG00000016429 (Rn)
Entrez Gene 2915 (Hs), 108071 (Mm), 24418 (Rn)
Human Protein Atlas ENSG00000168959 (Hs)
KEGG Gene hsa:2915 (Hs), mmu:108071 (Mm), rno:24418 (Rn)
OMIM 604102 (Hs)
RefSeq Nucleotide NM_001143831 (Hs), NM_000842 (Hs), NM_001081414 (Mm), NM_017012 (Rn)
RefSeq Protein NP_000833 (Hs), NP_001137303 (Hs), NP_001074883 (Mm), NP_058708 (Rn)
UniProtKB P41594 (Hs), Q3UVX5 (Mm), P31424 (Rn)
Wikipedia GRM5 (Hs)
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator mavoglurant
PDB Id:  4OO9
Ligand:  mavoglurant
Resolution:  2.6Å
Species:  Human
References:  23
Natural/Endogenous Ligands
L-glutamic acid
Comments: Other endogenous ligands include L-aspartic acid, L-serine-O-phosphate, NAAG and L-cysteine sulphinic acid

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
VU0424465 Rn Agonist 6.8 pEC50 81
⤷ pEC50 6.8 (EC50 1.71x10-7 M) [81]
VU0092273 Rn Agonist 5.9 pEC50 64
⤷ pEC50 5.9 (EC50 1.3x10-6 M) [64]
L-glutamic acid Hs Agonist 5.0 – 5.5 pEC50 71
⤷ pEC50 5.0 – 5.5 [71]
(S)-(+)-CBPG Rn Partial agonist 4.3 pEC50 55
⤷ pEC50 4.3 (EC50 4.7x10-5 M) [55]
quisqualate Rn Full agonist 7.5 pIC50 62
⤷ pIC50 7.5 [62]
L-glutamic acid Rn Full agonist 6.1 pIC50 62
⤷ pIC50 6.1 [62]
L-CCG-I Rn Full agonist 5.8 pIC50 62
⤷ pIC50 5.8 [62]
(1S,3R)-ACPD Rn Full agonist 5.7 pIC50 62
⤷ pIC50 5.7 [62]
ibotenic acid Rn Full agonist 5.7 pIC50 62
⤷ pIC50 5.7 [62]
3,5-DHPG Rn Partial agonist 5.4 pIC50 62
⤷ pIC50 5.4 [62]
(S)-3HPG Rn Partial agonist 5.0 pIC50 62
⤷ pIC50 5.0 [62]
CHPG Hs Full agonist 3.4 pIC50 62
⤷ pIC50 3.4 [62]
View species-specific agonist tables
Agonist Comments
Indicated affinities were determined by displacement studies of [3H]quisqualate bound on HEK cell membranes expressing a recombinant rat mGlu5. This is the only study describing affinity values for these compounds. More information on agonist potencies determined from functional studies can be obtained from [83]. So far no differences have been reported for the agonist affinities between the rat and the human receptor.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[11C]JNJ-16567083 Rn Antagonist 5.6 pKi 37
⤷ pKi 5.6 (Ki 2.366x10-6 M) [37]
methoxy-MPEP Hs Antagonist 8.4 pIC50 29
⤷ pIC50 8.4 (IC50 3.6x10-9 M) [29]
Description: [3H]-M-MPEP displacement assay.
ACDPP Hs Antagonist 6.9 pIC50 6
⤷ pIC50 6.9 [6]
(S)-4C3HPG Rn Antagonist 5.6 pIC50 62
⤷ pIC50 5.6 [62]
LY341495 Hs Antagonist 5.1 pIC50 43
⤷ pIC50 5.1 [43]
DCG-IV Rn Antagonist 4.7 pIC50 62
⤷ pIC50 4.7 [62]
(S)-4CPG Rn Antagonist 4.6 pIC50 62
⤷ pIC50 4.6 [62]
(+)-MCPG Rn Antagonist 3.7 pIC50 62
⤷ pIC50 3.7 [62]
View species-specific antagonist tables
Antagonist Comments
Indicated affinities were determined by displacement studies of [3H]quisqualate bound on HEK cell membranes expressing a recombinant rat mGlu5 (except for LY341495 value determined from functional studies). This is the only study describing affinity values for these compounds.

More information on agonist potencies determined from functional studies can be obtained from [83]. So far no differences have been reported for the antagonist affinities between the rat and the human receptor.

Surprisingly, although LY367385 and AIDA displace Quisqualate binding, no antagonistic activity of these compounds have been observed in functional studies (see [83]). (S)-4C3HPG has been reported to have slight partial agonist activity at this receptor [40].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
VU0483605 Rn Positive 6.5 pKB 35
⤷ pKB 6.5 [35]
GS39783 Rn Neutral 6.3 pKB 35
⤷ pKB 6.3 [35]
PHCCC Rn Neutral 5.6 pKB 35
⤷ pKB 5.6 [35]
AZ12216052 Rn Positive 5.4 pKB 35
⤷ pKB 5.4 [35]
NPS 2143 Rn Positive 5.1 pKB 35
⤷ pKB 5.1 [35]
CPCCOEt Rn Neutral 4.9 pKB 35
⤷ pKB 4.9 [35]
CGP7930 Rn Positive 4.8 pKB 35
⤷ pKB 4.8 [35]
[3H]CTEP Rn Negative 8.8 pKd 47
⤷ pKd 8.8 (Kd 1.5x10-9 M) [47]
[3H]CTEP Hs Negative 8.8 pKd 47
⤷ pKd 8.8 (Kd 1.7x10-9 M) [47]
[3H]CTEP Mm Negative 8.7 pKd 47
⤷ pKd 8.7 (Kd 1.8x10-9 M) [47]
[3H]methoxy-PEPy Rn Negative 8.5 pKd 20
⤷ pKd 8.5 (Kd 3.4x10-9 M) [20]
[3H]methoxymethyl-MTEP Rn Negative 7.7 pKd 20
⤷ pKd 7.7 (Kd 2x10-8 M) [20]
[3H]fenobam Hs Negative 7.5 pKd 74
⤷ pKd 7.5 [74]
[3H]fenobam Rn Negative 7.3 pKd 74
⤷ pKd 7.3 [74]
compound 20 [PMID: 16439120] Rn Negative 9.0 pKi 13
⤷ pKi 9.0 (Ki 1x10-9 M) [13]
BOMA Hs Negative 8.5 pKi 99
⤷ pKi 8.5 [99]
AZD9272 Hs Negative 8.4 pKi 75
⤷ pKi 8.4 (Ki 3.8x10-9 M) [75]
GRN-529 Rn Negative 8.3 pKi 38
⤷ pKi 8.3 (Ki 5.4x10-9 M) [38]
CTEP Mm Negative 8.0 pKi 47
⤷ pKi 8.0 (Ki 9.5x10-9 M) [47]
compound 26 [PMID: 16439120] Rn Negative 8.0 pKi 13
⤷ pKi 8.0 (Ki 1x10-8 M) [13]
compound 30 [PMID: 21757343] Hs Negative 7.9 pKi 100
⤷ pKi 7.9 (Ki 1.2x10-8 M) [100]
compound 10 [PMID: 15482906] Hs Negative 7.9 pKi 36
⤷ pKi 7.9 (Ki 1.2x10-8 M) [36]
CTEP Rn Negative 7.9 pKi 47
⤷ pKi 7.9 (Ki 1.26x10-8 M) [47]
compound 8 [PMID: 15482908] Rn Negative 7.8 pKi 89
⤷ pKi 7.8 (Ki 1.4x10-8 M) [89]
MTEP Hs Negative 7.8 pKi 10
⤷ pKi 7.8 (Ki 1.6x10-8 M) [10]
VU0285683 Rn Negative 7.8 pKi 76
⤷ pKi 7.8 (Ki 1.6x10-8 M) [76]
compound 29b [PMID: 20809633] Rn Negative 7.8 pKi 12
⤷ pKi 7.8 (Ki 1.7x10-8 M) [12]
CTEP Hs Negative 7.7 – 7.8 pKi 39,47
⤷ pKi 7.7 – 7.8 (Ki 2x10-8 – 1.64x10-8 M) [39,47]
compound 10 [PMID: 15482908] Rn Negative 7.7 pKi 89
⤷ pKi 7.7 (Ki 1.9x10-8 M) [89]
compound 23 [PMID: 17590335] Rn Negative 7.7 pKi 57
⤷ pKi 7.7 (Ki 2.2x10-8 M) [57]
AZD6538 Hs Negative 7.6 pKi 75
⤷ pKi 7.6 (Ki 2.8x10-8 M) [75]
compound 24d [PMID: 23357634] Rn Negative 7.5 pKi 106
⤷ pKi 7.5 (Ki 3x10-8 M) [106]
basimglurant Hs Negative 7.4 pKi 39
⤷ pKi 7.4 (Ki 3.6x10-8 M) [39]
Description: Reduction of antagonist MPEP binding to mGlu5 receptors in vitro
compound 16m [PMID: 19931453] Hs Negative 7.4 pKi 90
⤷ pKi 7.4 (Ki 3.8x10-8 M) [90]
VU0366058 Rn Negative 7.1 pKi 61
⤷ pKi 7.1 (Ki 8.4x10-8 M) [61]
compound 16a [PMID: 14697765] Rn Negative 7.0 pKi 99
⤷ pKi 7.0 (Ki 9.1x10-8 M) [99]
compound 42 [PMID: 17189691] Rn Negative 7.0 pKi 14
⤷ pKi 7.0 (Ki 9.5x10-8 M) [14]
compound 8 [PMID: 20598884] Rn Negative 7.0 pKi 25
⤷ pKi 7.0 (Ki 1.02x10-7 M) [25]
VU-1545 Rn Positive 6.8 pKi 22
⤷ pKi 6.8 (Ki 1.56x10-7 M) [22]
compound 11a [PMID: 14697765] Rn Negative 6.8 pKi 99
⤷ pKi 6.8 (Ki 1.59x10-7 M) [99]
VU0360172 Rn Positive 6.7 pKi 76
⤷ pKi 6.7 (Ki 1.95x10-7 M) [76]
compound 27 [PMID: 20598884] Rn Negative 6.7 pKi 25
⤷ pKi 6.7 (Ki 2.06x10-7 M) [25]
VU-29 Rn Positive 6.6 pKi 16
⤷ pKi 6.6 (Ki 2.44x10-7 M) [16]
M-5MPEP Rn Negative 6.5 pKi 77
⤷ pKi 6.5 (Ki 3x10-7 M) [77]
Br-5MPEPy Rn Negative 6.5 pKi 77
⤷ pKi 6.5 (Ki 3x10-7 M) [77]
LSN2463359 Rn Positive 6.4 pKi 31
⤷ pKi 6.4 (Ki 3.77x10-7 M) [31]
5-MPEP Rn Neutral 6.4 pKi 77
⤷ pKi 6.4 [77]
compound 18 [PMID: 21927650] Rn Negative 6.3 pKi 48
⤷ pKi 6.3 (Ki 4.77x10-7 M) [48]
LSN2814617 Rn Positive 5.9 pKi 31
⤷ pKi 5.9 (Ki 1.34x10-6 M) [31]
5PAM523 Rn Positive 5.7 pKi 68
⤷ pKi 5.7 (Ki 2x10-6 M) [68]
CPPZ Rn Positive 5.5 pKi 91
⤷ pKi 5.5 (Ki 3.1x10-6 M) [91]
ADX-47273 Rn Positive 5.4 pKi 31
⤷ pKi 5.4 (Ki 3.65x10-6 M) [31]
cinacalcet Rn Positive 4.3 pKi 35
⤷ pKi 4.3 [35]
VU0424465 Rn Positive 8.8 pEC50 81
⤷ pEC50 8.8 (EC50 1.5x10-9 M) [81]
VU0404251 Rn Positive 8.1 pEC50 54
⤷ pEC50 8.1 (EC50 7.2x10-9 M) [54]
VU-29 Rn Positive 8.1 pEC50 16
⤷ pEC50 8.1 (EC50 9x10-9 M) [16]
VU-1545 Hs Positive 8.0 pEC50 22
⤷ pEC50 8.0 (EC50 9.6x10-9 M) [22]
VU0463841 Rn Negative 7.9 pEC50 2
⤷ pEC50 7.9 (EC50 1.3x10-8 M) [2]
compound 41 [PMID: 23434029] Hs Negative 7.9 pEC50 15
⤷ pEC50 7.9 (EC50 1.3x10-8 M) [15]
CDPPB Hs Positive 7.6 – 8.0 pEC50 44,49
⤷ pEC50 7.6 – 8.0 [44,49]
VU0360172 Rn Positive 7.8 pEC50 76
⤷ pEC50 7.8 (EC50 1.6x10-8 M) [76]
CDPPB Rn Positive 7.7 pEC50 49
⤷ pEC50 7.7 [49]
LSN2463359 Rn Positive 7.6 pEC50 31
⤷ pEC50 7.6 (EC50 2.4x10-8 M) [31]
LSN2463359 Hs Positive 7.5 pEC50 31
⤷ pEC50 7.5 (EC50 3.3x10-8 M) [31]
VU0357121 Rn Positive 7.5 pEC50 32
⤷ pEC50 7.5 (EC50 3.3x10-8 M) [32]
VU0092273 Rn Positive 7.5 pEC50 64
⤷ pEC50 7.5 (EC50 3.5x10-8 M) [64]
VU0240382 Rn Positive 7.4 pEC50 64
⤷ pEC50 7.4 (EC50 3.9x10-8 M) [64]
compound 47 [PMID: 21295468] Hs Positive 7.3 pEC50 96
⤷ pEC50 7.3 (EC50 5.01x10-8 M) [96]
LSN2814617 Hs Positive 7.3 pEC50 31
⤷ pEC50 7.3 (EC50 5.2x10-8 M) [31]
ADX-47273 Rn Positive 7.3 pEC50 31
⤷ pEC50 7.3 (EC50 5.5x10-8 M) [31]
VU0404251 Hs Positive 7.2 pEC50 54
⤷ pEC50 7.2 (EC50 7x10-8 M) [54]
LSN2814617 Rn Positive 7.0 pEC50 31
⤷ pEC50 7.0 (EC50 9.3x10-8 M) [31]
VU0361747 Rn Positive 6.9 pEC50 64
⤷ pEC50 6.9 (EC50 1.26x10-7 M) [64]
ADX-47273 Hs Positive 6.8 pEC50 31
⤷ pEC50 6.8 (EC50 1.57x10-7 M) [31]
5PAM523 Hs Positive 6.7 pEC50 68
⤷ pEC50 6.7 (EC50 2.01x10-7 M) [68]
5PAM523 Rn Positive 6.5 pEC50 68
⤷ pEC50 6.5 (EC50 3.11x10-7 M) [68]
NCFP Rn Positive 6.0 – 6.7 pEC50 63
⤷ pEC50 6.7 (EC50 2.14x10-7 M) EC50 with high mGlu5 expression [63]
pEC50 6.4 (EC50 3.7x10-7 M) EC50 with low mGlu5 expression [63]
pEC50 6.0 (EC50 9.69x10-7 M) EC50 from assay using rat astrocytes [63]
CPPZ Hs Positive 6.3 pEC50 91
⤷ pEC50 6.3 (EC50 5x10-7 M) [91]
VU0364289 Rn Positive 5.8 pEC50 107
⤷ pEC50 5.8 (EC50 1.6x10-6 M) [107]
SP203 Rn Negative 10.4 pIC50 87
⤷ pIC50 10.4 (IC50 3.6x10-11 M) [87]
compound 18 [PMID: 17723296] Rn Negative 9.1 pIC50 101
⤷ pIC50 9.1 (IC50 7.2x10-10 M) [101]
compound 23 [PMID: 17590335] Rn Negative 9.1 pIC50 57
⤷ pIC50 9.1 (IC50 8x10-10 M) [57]
MTEB Hs Negative 8.7 pIC50 99
⤷ pIC50 8.7 [99]
GRN-529 Hs Negative 8.6 pIC50 38
⤷ pIC50 8.6 (IC50 2.6x10-9 M) [38]
compound 8 [PMID: 15482908] Hs Negative 8.4 pIC50 89
⤷ pIC50 8.4 (IC50 3.9x10-9 M) [89]
[3H]M-MPEP Hs Negative 8.3 – 8.4 pIC50 29,65
⤷ pIC50 8.4 [29]
pIC50 8.3 [65]
compound 10 [PMID: 15482906] Hs Negative 8.2 pIC50 36
⤷ pIC50 8.2 (IC50 6.7x10-9 M) [36]
AZD9272 Hs Negative 8.1 pIC50 75
⤷ pIC50 8.1 (IC50 7.6x10-9 M) [75]
alloswitch-1 Rn Negative 8.1 pIC50 73
⤷ pIC50 8.1 (IC50 8.6x10-9 M) [73]
Description: Inhibition of agonist-induced IP accumulation.
CTEP Hs Negative 7.9 – 8.2 pIC50 47
⤷ pIC50 7.9 – 8.2 (IC50 1.14x10-8 – 6.4x10-9 M) [47]
compound 30 [PMID: 21757343] Rn Negative 7.9 pIC50 100
⤷ pIC50 7.9 (IC50 1.2x10-8 M) [100]
VU0463841 Rn Negative 7.9 pIC50 2
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [2]
AZD6538 Hs Negative 7.9 pIC50 75
⤷ pIC50 7.9 (IC50 1.34x10-8 M) [75]
compound 29b [PMID: 20809633] Hs Negative 7.8 pIC50 12
⤷ pIC50 7.8 (IC50 1.6x10-8 M) [12]
compound 30 [PMID: 21757343] Hs Negative 7.8 pIC50 100
⤷ pIC50 7.8 (IC50 1.7x10-8 M) [100]
compound 24 [PMID: 23374867] Hs Negative 7.7 pIC50 33
⤷ pIC50 7.7 (IC50 1.9x10-8 M) [33]
[14C]MTEP Rn Negative 7.7 pIC50 3
⤷ pIC50 7.7 [3]
dipraglurant Hs Negative 7.7 pIC50 15
⤷ pIC50 7.7 (IC50 2x10-8 M) [15]
compound 16a [PMID: 14697765] Hs Negative 7.7 pIC50 99
⤷ pIC50 7.7 (IC50 2.2x10-8 M) [99]
compound 24d [PMID: 23357634] Hs Negative 7.6 pIC50 106
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [106]
VU0285683 Rn Negative 7.6 pIC50 76
⤷ pIC50 7.6 (IC50 2.44x10-8 M) [76]
MPEP Hs Negative 7.4 – 7.7 pIC50 29-30
⤷ pIC50 7.4 – 7.7 [29-30]
compound 13 [PMID: 15686941] Hs Negative 7.6 pIC50 6
⤷ pIC50 7.6 (IC50 2.8x10-8 M) [6]
methoxymethyl-MTEP Rn Negative 7.5 pIC50 3
⤷ pIC50 7.5 (IC50 3x10-8 M) [3]
compound 16m [PMID: 19931453] Hs Negative 7.5 pIC50 90
⤷ pIC50 7.5 (IC50 3.2x10-8 M) [90]
compound 11a [PMID: 14697765] Hs Negative 7.4 pIC50 99
⤷ pIC50 7.4 (IC50 4.1x10-8 M) [99]
GSK2210875 Hs Negative 7.4 pIC50 70