GRM3

Summary

GRM3 (glutamate metabotropic receptor 3, HGNC:4595) is a protein-coding gene on chromosome 7q21.11-q21.12, encoding Metabotropic glutamate receptor 3 (Q14832). G-protein coupled receptor for glutamate.

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities.

Source: NCBI Gene 2913 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 64 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• MANE Select transcript: NM_000840

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4595
Approved symbol	GRM3
Name	glutamate metabotropic receptor 3
Location	7q21.11-q21.12
Locus type	gene with protein product
Status	Approved
Aliases	GPRC1C, mGlu3, MGLUR3
Ensembl gene	ENSG00000198822
Ensembl biotype	protein_coding
OMIM	601115
Entrez	2913

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000361669, ENST00000421579, ENST00000439827, ENST00000441140, ENST00000454217, ENST00000924209, ENST00000953115

RefSeq mRNA: 2 — MANE Select: NM_000840 NM_000840, NM_001363522

CCDS: CCDS5600, CCDS87515

Canonical transcript exons

ENST00000361669 — 6 exons

Exon	Start	End
ENSE00000700691	86838839	86839905
ENSE00001254406	86786261	86787116
ENSE00001254415	86765006	86765613
ENSE00001621224	86864282	86864879
ENSE00001893578	86643909	86644872
ENSE00003523712	86850370	86850544

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 97.89.

FANTOM5 (CAGE): breadth broad, TPM avg 5.0196 / max 284.8713, expressed in 234 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
79374	1.5601	139
79379	1.5148	118
79377	1.0828	162
79382	0.2014	76
79376	0.1585	71
79373	0.1578	73
79381	0.1532	69
79378	0.0773	50
79375	0.0750	51
79380	0.0387	30

Top tissues by expression

254 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	97.89	gold quality
middle frontal gyrus	UBERON:0002702	97.50	gold quality
cortical plate	UBERON:0005343	97.25	gold quality
buccal mucosa cell	CL:0002336	96.51	gold quality
corpus callosum	UBERON:0002336	95.78	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.40	gold quality
inferior vagus X ganglion	UBERON:0005363	95.08	gold quality
Brodmann (1909) area 10	UBERON:0013541	95.00	gold quality
putamen	UBERON:0001874	94.03	gold quality
orbitofrontal cortex	UBERON:0004167	93.83	gold quality
CA1 field of hippocampus	UBERON:0003881	93.35	gold quality
caudate nucleus	UBERON:0001873	93.33	gold quality
prefrontal cortex	UBERON:0000451	93.20	gold quality
entorhinal cortex	UBERON:0002728	93.16	gold quality
frontal pole	UBERON:0002795	92.93	gold quality
superior frontal gyrus	UBERON:0002661	92.75	gold quality
parietal lobe	UBERON:0001872	92.49	gold quality
postcentral gyrus	UBERON:0002581	92.36	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.66	gold quality
frontal cortex	UBERON:0001870	91.60	gold quality
subthalamic nucleus	UBERON:0001906	91.50	gold quality
nucleus accumbens	UBERON:0001882	91.49	gold quality
telencephalon	UBERON:0001893	91.30	gold quality
ventral tegmental area	UBERON:0002691	91.20	gold quality
neocortex	UBERON:0001950	91.06	gold quality
lateral globus pallidus	UBERON:0002476	90.90	gold quality
cerebral cortex	UBERON:0000956	90.84	gold quality
occipital lobe	UBERON:0002021	90.72	gold quality
globus pallidus	UBERON:0001875	90.48	gold quality
medulla oblongata	UBERON:0001896	90.46	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	80.92
E-ANND-3	yes	4.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

103 targeting GRM3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-300	99.92	71.76	2856

Literature-anchored findings (GeneRIF, showing 40)

• results define a microenvironment within the binding pocket that encompasses several positively charged amino acids that recognize the negatively charged phosphonate group of l-AP4 or the endogenous compound l-serine-O-phosphate. (PMID:11744707)
• genetic variation in the metabotropic glutamate receptor 3 gene that might contribute to genetic predisposition to schizophrenia and/or bipolar affective disorder (PMID:11840505)
• At least one susceptibility locus for schizophrenia is situated within or very close to the GRM3 region in Japanese patients. (PMID:12782962)
• mGluR3 and mGluR5 can critically and differentially modulate the expression of glutamate transporters and may represent interesting pharmacological targets to regulate the extracellular levels of glutamate in pathological conditions. (PMID:12786977)
• glial progenitor cells present in the adult human CNS express mGluR3 and mGluR5a (PMID:15158450)
• definition of the essential requirements for ligand binding to the extracellular domain of mGluR3 and highlight parameters important for the optimization of receptor expression in mammalian cells (PMID:15178451)
• Reduction of mGluR3 immunopositive product in the stratum lacunosum moleculare of hippocampal CA1 is a consequence of neuronal loss in either the entorhinal cortex or CA1 area of the hippocampus. (PMID:15246118)
• Data point to a specific molecular pathway by which metabotropic glutamate receptor GRM3 alters glutamate neurotransmission, prefrontal and hippocampal physiology and cognition, and thereby increased risk for schizophrenia. (PMID:15310849)
• MGluR3 modulate the release of IL-6 in the presence of IL-1beta, supporting the role of mGluR3 in the regulation of the inflammatory and immune response associated with gliosis. (PMID:15652990)
• GRM3 polymorphism may be associated with negative symptom improvement in persons with schizophrenia treated with olanzapine. (PMID:15913960)
• The existence of the GRM3Delta4 isoform is relevant in the light of the reported association of non-coding single nucleotide polymorphisms (SNPs) in GRM3 with schizophrenia. (PMID:16417579)
• SNPs in RGS4, G72, GRM3, and DISC1 showed evidence for significant statistical epistasis with COMT. (PMID:17006672)
• mGlu3 receptor levels are altered in schizophrenia (PMID:17531207)
• extend putative brain dopaminergic and glutamatergic relationships indexed by catechol-O-methyltransferase and GRM3 to a systems-level interaction in human cortical circuits implicated in working memory dysfunction such as in schizophrenia (PMID:17636131)
• we genotyped rs274622 in the promoter region of GRM3. In the present study, none of these polymorphisms were associated with schizophrenia (PMID:17948896)
• Single nucleotide polymorphisms are not assoiated with schziphrenia. (PMID:18075480)
• The study of DNA sequence variants in the GRM3 gene did not provide further support for genetic association with schizophrenia or for correlation with cognitive deficits. (PMID:18197082)
• An exon 3 single nucleotide polymorphism (SNP) in GRM3 predicts increased splicing of the fourth exon and may contribute to risk for schizophrenia by modulating GRM3 splicing. (PMID:18256595)
• The results of the present study indicate that the rs6465084 functional polymorphism in GRM3 does not contribute to genetic susceptibility to schizophrenia. (PMID:18412850)
• these data implicate mGluR3 in aetiological, pathophysiological and pharmacotherapeutic aspects of schizophrenia–REVIEW (PMID:18541626)
• Our results provide further evidence for the potential importance of the glutamate receptor GRM3 in schizophrenia, and indicate that the novel antipsychotic LY2140023 may actually be targeting a pathogenic pathway of schizophrenia. (PMID:18614340)
• The expression of mGluR2, 3 in DA cells provide a mechanism for glutamate to modulate dopamine release in the human brain and this species-specific difference may be critical to understanding rodent models in schizophrenia. (PMID:18853337)
• An association is found between one marker (rs6465084) in glutamate receptor gene GRM3 and Japanese patients with major depressive disorder. (PMID:19386277)
• These data suggest that Glutamate receptor metabotropic 3 glutamate metabotropic receptor is disrupted in the AH in schizophrenia and localize the defect to the CA1 and CA3 regions. (PMID:19403271)
• present Scandinavian results do not verify previous associations between the analyzed DTNBP1, NRG1, DAO, DAOA, and GRM3 gene polymorphisms and schizophrenia (PMID:19439994)
• Findings strongly suggest that the genetic variation (rs17676277 and three haplotypes) in the metabotropic glutamate receptor 3is related to cognitive setshifting in healthy individuals independent of working memory. (PMID:20132315)
• This study suggested a gene-environment (G x E) interaction between GRM3 gene variants and severe obstetric complications on hippocampus volume, independent of a diagnosis of schizophrenia. (PMID:20638435)
• Psychosis and relapse in bipolar disorder are related to GRM3, DAOA, and GRIN2B genotype in a Caucasian and mixed-ancestry South African pilot study. (PMID:20957330)
• Suggest a genetic association exists between SNPs in several genes, such as HTR2A and NRG1, and response to mGlu2/3 agonist LY2140023 treatment in schizophrenia. (PMID:21173788)
• Polymorphisms in the GRM3 gene may be associated with refractory global psychosis symptoms but not negative symptoms in persons with schizophrenia. (PMID:21344500)
• data support the idea that glutamate release in the vental tegmental area(VTA) is critically involved in cocaine-induced reinstatement; loss of mGluR2/3-mediated regulation of glutamate release in the VTA may critically contribute to the risk of relapse (PMID:21881873)
• Melanoma cells expressing mutant GRM3 had reduced cell growth and cellular migration after short hairpin RNA-mediated knockdown of GRM3 or treatment with a selective MEK inhibitor, AZD-6244, which is currently being used in phase 2 clinical trials (PMID:21946352)
• These results suggest that variations in GRM3 genotype modulate the auditory cortical response to phoneme change in humans. (PMID:22022368)
• glutamate system dysfunction may play a role in the prefrontal functional abnormalities seen in alcoholism. certain GRM3 SNP genotypes may further lower NAA/Cr levels and executive function in addition to the effect of alcohol. (PMID:22909248)
• The transcript of mGlu3 receptors should be measured in tumor specimens for a correct prediction of patients’ survival in response to temozolomide treatment. (PMID:23175182)
• analysis suggested that mGluR3 is the major mGlu receptor expressed by adult cortical astrocytes, whereas the expression of other mGluRs was low or absent (PMID:23307741)
• Kozak sequence variant associated with bipolar disorder (PMID:23575746)
• report we describe a novel neuroprotective function of mGlu3 receptors related to their ability to promote the non-amyloidogenic pathway of APP cleavage in astrocytes, thus enhancing sAPPalpha production (PMID:24291464)
• Data indicate that metabotropic glutamate receptor subtype 3 (mGluR3) polymorphisms do not contribute to genetic susceptibility to schizophrenia and depression, but they confer an increased risk of heroin dependence (HD) in a Chinese population. (PMID:24498053)
• results supplied the first evidence that the polymorphism of GRM3 gene associates with the morbidity of alcohol dependence in human beings. (PMID:24585043)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	grm3	ENSDARG00000031712
mus_musculus	Grm3	ENSMUSG00000003974
rattus_norvegicus	Grm3	ENSRNOG00000005519
drosophila_melanogaster	mtt	FBGN0050361
caenorhabditis_elegans		WBGENE00003232
caenorhabditis_elegans		WBGENE00021152

Paralogs (7): GRM6 (ENSG00000113262), GRM4 (ENSG00000124493), GRM1 (ENSG00000152822), GRM2 (ENSG00000164082), GRM5 (ENSG00000168959), GRM8 (ENSG00000179603), GRM7 (ENSG00000196277)

Protein

Protein identifiers

Metabotropic glutamate receptor 3 — Q14832 (reviewed: Q14832)

All UniProt accessions (5): Q14832, A4D1D0, C9J2I2, C9JIT1, C9JUH9

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with TAMALIN.

Subcellular location. Cell membrane.

Tissue specificity. Detected in brain cortex, thalamus, subthalamic nucleus, substantia nigra, hypothalamus, hippocampus, corpus callosum, caudate nucleus and amygdala.

Miscellaneous. Appears to be membrane-associated, despite the absence of the seven-transmembrane domain.

Similarity. Belongs to the G-protein coupled receptor 3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q14832-1	1	yes
Q14832-2	2, GRM3Delta4

RefSeq proteins (2): NP_000831, NP_001350451 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000162	GPCR_3_mtglu_rcpt	Family
IPR000337	GPCR_3	Family
IPR001234	GPCR_3_mGluR3	Family
IPR001828	ANF_lig-bd_rcpt	Domain
IPR011500	GPCR_3_9-Cys_dom	Domain
IPR017978	GPCR_3_C	Domain
IPR017979	GPCR_3_CS	Conserved_site
IPR028082	Peripla_BP_I	Homologous_superfamily
IPR038550	GPCR_3_9-Cys_sf	Homologous_superfamily
IPR050726	mGluR	Family

Pfam: PF00003, PF01094, PF07562

UniProt features (118 total): strand 37, helix 28, turn 12, topological domain 8, disulfide bond 8, transmembrane region 7, binding site 5, glycosylation site 4, sequence conflict 4, splice variant 2, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
3SM9	X-RAY DIFFRACTION	2.26
4XAR	X-RAY DIFFRACTION	2.26
8JCU	ELECTRON MICROSCOPY	2.8
8JD2	ELECTRON MICROSCOPY	2.8
6B7H	X-RAY DIFFRACTION	2.82
5CNM	X-RAY DIFFRACTION	2.84
8JCY	ELECTRON MICROSCOPY	2.9
8JCW	ELECTRON MICROSCOPY	3
8JCX	ELECTRON MICROSCOPY	3
8JCZ	ELECTRON MICROSCOPY	3
5CNK	X-RAY DIFFRACTION	3.15
8JD0	ELECTRON MICROSCOPY	3.3
8JD3	ELECTRON MICROSCOPY	3.3
8JCV	ELECTRON MICROSCOPY	3.4
7WIH	ELECTRON MICROSCOPY	3.68
8JD1	ELECTRON MICROSCOPY	3.7
9II2	ELECTRON MICROSCOPY	3.7
7WI6	ELECTRON MICROSCOPY	3.71
9II3	ELECTRON MICROSCOPY	3.9
7WI8	ELECTRON MICROSCOPY	4.17

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14832-F1	85.44	0.58

Antibody-complex structures (SAbDab): 2 — 9II2, 9II3

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 151; 172–174; 222; 301; 389

Disulfide bonds (8): 57–99, 240–527, 361–373, 412–419, 509–528, 513–531, 534–546, 549–562

Glycosylation sites (4): 209, 292, 414, 439

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events
R-HSA-420499	Class C/3 (Metabotropic glutamate/pheromone receptors)

MSigDB gene sets: 203 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, MODULE_274, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, TTTGTAG_MIR520D, CREBP1_Q2, GOBP_G_PROTEIN_COUPLED_GLUTAMATE_RECEPTOR_SIGNALING_PATHWAY, AP2_Q3, RIZKI_TUMOR_INVASIVENESS_3D_DN, GGGTGGRR_PAX4_03, FOXD3_01, GOBP_CELL_CELL_SIGNALING, CREB_Q4, EVI1_05, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, IRF7_01

GO Biological Process (12): negative regulation of adenylate cyclase activity (GO:0007194), G protein-coupled glutamate receptor signaling pathway (GO:0007216), chemical synaptic transmission (GO:0007268), gene expression (GO:0010467), cellular response to stress (GO:0033554), regulation of synaptic transmission, glutamatergic (GO:0051966), postsynaptic modulation of chemical synaptic transmission (GO:0099170), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), adenylate cyclase-inhibiting G protein-coupled glutamate receptor signaling pathway (GO:0007196), modulation of chemical synaptic transmission (GO:0050804)

GO Molecular Function (6): group II metabotropic glutamate receptor activity (GO:0001641), G protein-coupled receptor activity (GO:0004930), calcium channel regulator activity (GO:0005246), glutamate receptor activity (GO:0008066), scaffold protein binding (GO:0097110), protein binding (GO:0005515)

GO Cellular Component (10): plasma membrane (GO:0005886), postsynaptic density (GO:0014069), axon (GO:0030424), presynaptic membrane (GO:0042734), dendritic spine (GO:0043197), postsynaptic membrane (GO:0045211), astrocyte projection (GO:0097449), glutamatergic synapse (GO:0098978), membrane (GO:0016020), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
postsynapse	3
G protein-coupled receptor signaling pathway	2
cellular response to stimulus	2
modulation of chemical synaptic transmission	2
adenylate cyclase inhibiting G protein-coupled glutamate receptor activity	2
transmembrane signaling receptor activity	2
synaptic membrane	2
adenylate cyclase activity	1
negative regulation of catalytic activity	1
regulation of adenylate cyclase activity	1
glutamate receptor signaling pathway	1
G protein-coupled glutamate receptor activity	1
anterograde trans-synaptic signaling	1
macromolecule biosynthetic process	1
response to stress	1
synaptic transmission, glutamatergic	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
G protein-coupled glutamate receptor signaling pathway	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
calcium channel activity	1
ion channel regulator activity	1
glutamate binding	1
protein binding	1
binding	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1
neuron projection	1
presynapse	1
dendrite	1

Protein interactions and networks

STRING

2765 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRM3	GRIN2A	Q12879	924
GRM3	GRIN2B	Q13224	869
GRM3	GRIA1	P42261	833
GRM3	ADCY8	P40145	830
GRM3	GRIA4	P48058	803
GRM3	CAMK2G	Q13555	787
GRM3	COMT	P21964	732
GRM3	PRKCA	P17252	715
GRM3	GRIN1	P35437	704
GRM3	GRIK1	P39086	703
GRM3	GRIA2	P42262	685
GRM3	GRIN3A	Q8TCU5	680
GRM3	GRIK5	Q16478	675
GRM3	GRIN2D	O15399	664
GRM3	BDNF	P23560	660

IntAct

24 interactions, top by confidence:

A	B	Type	Score
GRM3	SPOP	psi-mi:“MI:0915”(physical association)	0.450
SPOP	GRM3	psi-mi:“MI:2364”(proximity)	0.450
GRM3	SPOP	psi-mi:“MI:2364”(proximity)	0.450
GRM3	SMC1A	psi-mi:“MI:0915”(physical association)	0.400
AKT1	GRM3	psi-mi:“MI:2364”(proximity)	0.270
BRAF	GRM3	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	GRM3	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	GRM3	psi-mi:“MI:2364”(proximity)	0.270
GRM3	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	GRM3	psi-mi:“MI:2364”(proximity)	0.270
GRM3	PTEN	psi-mi:“MI:2364”(proximity)	0.270
GRM3	TP53	psi-mi:“MI:2364”(proximity)	0.270
GRM3	PTPN11	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (15): GRM3 (Synthetic Lethality), PPM1A (Two-hybrid), PPM1A (Affinity Capture-Western), GRM3 (Reconstituted Complex), GRM3 (Reconstituted Complex), GRM3 (Affinity Capture-Western), GRM3 (Affinity Capture-Western), GRM3 (Proximity Label-MS), GRIP1 (Two-hybrid), PICK1 (Two-hybrid), SDCBP (Reconstituted Complex), PICK1 (Reconstituted Complex), GRIP1 (Reconstituted Complex), GRM3 (Affinity Capture-MS), GRM3 (Affinity Capture-MS)

ESM2 similar proteins: A0A2I4HXH5, A5D6U8, B3A0N5, B6EWW8, E0D877, F8S0Z7, O00462, O35409, P05089, P15693, P19492, P21588, P21589, P29240, P31422, P42263, P49614, P49900, P50635, P52307, P70627, P83456, P83852, Q05927, Q14832, Q1ZZH1, Q29444, Q2KJ64, Q4FZV0, Q561R9, Q5R979, Q5RAL3, Q5RFI5, Q5TVM9, Q5XGR8, Q61503, Q641Z7, Q6AYS4, Q6PCE3, Q8CAA7

Diamond homologs: O00222, O15303, O62714, P23385, P31421, P31422, P31423, P31424, P35349, P35400, P41180, P41594, P47743, P48442, P70579, P91685, P97772, Q09630, Q13255, Q14416, Q14831, Q14832, Q14833, Q14BI2, Q1ZZH0, Q1ZZH1, Q3UVX5, Q5NCH9, Q5RAL3, Q5RDQ8, Q68ED2, Q68EF4, Q863I4, Q9QY96, Q9QYS2, P35384, A3QNZ8, A3QNZ9, A3QP00, A3QP01

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
“(1R,4S,5S,6S)-4-amino-2,2-dioxo-2$l^{6}-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid”	up-regulates	GRM3	“chemical activation”
“glutamic acid”	“up-regulates activity”	GRM3	“chemical activation”
GRM3	“up-regulates activity”	GNAS	binding
GRM3	up-regulates	Excitatory_synaptic_transmission
GRM3	“up-regulates quantity”	calcium(2+)	relocalization

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — CHRCC, ESCA, MEL.

Clinical variants and AI predictions

ClinVar

64 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	7
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1594 predictions. Top by Δscore:

Variant	Effect	Δscore
7:86660007:A:T	donor_gain	1.0000
7:86786257:CTA:C	acceptor_loss	1.0000
7:86786258:TA:T	acceptor_loss	1.0000
7:86786259:A:AG	acceptor_gain	1.0000
7:86786259:A:G	acceptor_loss	1.0000
7:86786259:AG:A	acceptor_gain	1.0000
7:86786259:AGGT:A	acceptor_gain	1.0000
7:86786259:AGGTG:A	acceptor_gain	1.0000
7:86786260:G:GT	acceptor_gain	1.0000
7:86786260:GG:G	acceptor_gain	1.0000
7:86786260:GGT:G	acceptor_gain	1.0000
7:86786260:GGTG:G	acceptor_gain	1.0000
7:86786260:GGTGG:G	acceptor_gain	1.0000
7:86838823:A:AG	acceptor_gain	1.0000
7:86838824:C:G	acceptor_gain	1.0000
7:86838831:T:G	acceptor_gain	1.0000
7:86787115:GG:G	donor_gain	0.9900
7:86787116:GG:G	donor_gain	0.9900
7:86787116:GGTAA:G	donor_loss	0.9900
7:86787118:TAAGC:T	donor_loss	0.9900
7:86838828:A:AG	acceptor_gain	0.9900
7:86838830:A:AG	acceptor_gain	0.9900
7:86839904:GA:G	donor_gain	0.9900
7:86850543:GT:G	donor_gain	0.9900
7:86850545:G:GG	donor_gain	0.9900
7:86644039:A:T	donor_gain	0.9800
7:86787117:G:GG	donor_gain	0.9800
7:86838838:GCTCC:G	acceptor_gain	0.9800
7:86839906:G:GG	donor_gain	0.9800
7:86850364:TTGTA:T	acceptor_loss	0.9800

AlphaMissense

5810 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:86765441:G:A	C99Y	1.000
7:86765442:T:G	C99W	1.000
7:86765606:C:A	S154Y	1.000
7:86765606:C:T	S154F	1.000
7:86786264:G:C	A158P	1.000
7:86786271:T:C	L160P	1.000
7:86786274:T:C	L161P	1.000
7:86786282:T:C	F164L	1.000
7:86786284:C:A	F164L	1.000
7:86786284:C:G	F164L	1.000
7:86786300:A:C	S170R	1.000
7:86786302:C:A	S170R	1.000
7:86786302:C:G	S170R	1.000
7:86786310:C:A	S173Y	1.000
7:86786310:C:T	S173F	1.000
7:86786358:G:T	R189M	1.000
7:86786420:T:A	W210R	1.000
7:86786420:T:C	W210R	1.000
7:86786510:T:A	C240S	1.000
7:86786511:G:C	C240S	1.000
7:86786699:T:A	W303R	1.000
7:86786699:T:C	W303R	1.000
7:86839039:T:A	C509S	1.000
7:86839040:G:C	C509S	1.000
7:86839101:G:C	W529C	1.000
7:86839101:G:T	W529C	1.000
7:86765269:G:A	G42R	0.999
7:86765269:G:C	G42R	0.999
7:86765269:G:T	G42W	0.999
7:86765270:G:A	G42E	0.999

dbSNP variants (sampled 300 via entrez): RS1000010616 (7:86729603 A>G,T), RS1000011289 (7:86831072 G>A), RS1000020645 (7:86741268 C>T), RS1000041374 (7:86696607 T>C), RS1000048024 (7:86799986 C>T), RS1000061972 (7:86818104 A>C,G), RS1000097261 (7:86823135 A>G), RS1000125822 (7:86722960 C>A,T), RS1000141673 (7:86653581 A>G), RS1000144583 (7:86775305 C>T), RS1000146996 (7:86736891 G>A), RS1000171835 (7:86678229 A>G), RS1000187239 (7:86825367 A>G), RS1000190647 (7:86843209 C>A), RS1000209508 (7:86718167 C>T)

Disease associations

OMIM: gene MIM:601115 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001462_1	Brachial circumference	7.000000e-06
GCST002539_66	Schizophrenia	3.000000e-10
GCST003831_28	Asthma	2.000000e-06
GCST004521_94	Autism spectrum disorder or schizophrenia	1.000000e-10
GCST004946_82	Schizophrenia	3.000000e-10
GCST005232_143	Neuroticism	2.000000e-09
GCST005655_5	Seborrheic dermatitis	5.000000e-07
GCST005655_7	Seborrheic dermatitis	2.000000e-06
GCST006291_17	Spherical equivalent or myopia (age of diagnosis)	4.000000e-08
GCST006803_16	Schizophrenia	4.000000e-14
GCST006940_174	Neurociticism	1.000000e-08
GCST006950_68	Feeling worry	4.000000e-08
GCST007201_170	Schizophrenia	3.000000e-10
GCST007201_72	Schizophrenia	4.000000e-10
GCST008595_186	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	8.000000e-09
GCST009600_110	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3.000000e-10
GCST010002_257	Refractive error	2.000000e-16
GCST010278_1	Hand grip strength (Mahalanobis distance)	5.000000e-08
GCST010278_2	Hand grip strength (Mahalanobis distance)	6.000000e-07
GCST010278_6	Hand grip strength (Mahalanobis distance)	3.000000e-06
GCST011741_53	LDL cholesterol levels in HIV infection	8.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0004847	age at onset
EFO:0009589	worry measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0006941	grip strength measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2888 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 929,874 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL575060	GLUTAMIC ACID	3	929,756
CHEMBL8759	EGLUMETAD	2	81
CHEMBL375611	LY404039	1	37

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

9 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs13242038	Other	3	heroin	Heroin Dependence
rs1468412	Toxicity	3	antipsychotics	Schizophrenia
rs1990040	Other	3	heroin	Heroin Dependence
rs2189814	Other	3	heroin	Heroin Dependence
rs274618	Other	3	heroin	Heroin Dependence
rs274622	Other	3	heroin	Heroin Dependence
rs6465084	Efficacy	3	antipsychotics	Schizophrenia
rs724226	Efficacy	3	risperidone	Schizophrenia
rs724226	Other	3	heroin	Heroin Dependence

PharmGKB variants

18 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs274618	GRM3	3	2.50	1	heroin
rs274622	GRM3	3	2.50	1	heroin
rs724226	GRM3	3	2.50	2	risperidone;heroin
rs917071	GRM3		0.00	0
rs1468412	GRM3	3	2.25	1	antipsychotics
rs1989796	GRM3		0.00	0
rs1990040	GRM3	3	2.50	1	heroin
rs2189814	GRM3	3	2.50	1	heroin
rs2237558	GRM3		0.00	0
rs2237562	GRM3		0.00	0
rs2282966	GRM3		0.00	0
rs2299214	GRM3		0.00	0
rs2299225	GRM3		0.00	0
rs6465084	GRM3	3	5.25	1	antipsychotics
rs6465088	GRM3		0.00	0
rs6947784	GRM3		0.00	0
rs7789655	GRM3		0.00	0
rs13242038	GRM3	3	2.50	1	heroin

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Metabotropic glutamate receptors

Most potent curated ligand interactions (25 total), top 25:

Ligand	Action	Affinity	Parameter
[3H]LY341495	Antagonist	9.1	pKd
LY341495	Antagonist	8.9	pKi
eglumegad	Full agonist	8.9	pKi
MGS0039	Antagonist	8.4	pKi
MNI-136	Negative	7.7	pIC50
MNI-137	Negative	7.7	pIC50
MNI-135	Negative	7.5	pEC50
L-CCG-I	Full agonist	7.4	pKi
DCG-IV	Full agonist	7.2	pKi
LY2389575	Negative	6.72	pIC50
Ro4491533	Negative	6.6	pIC50
LY395756	Antagonist	6.52	pKi
VU0650786	Negative	6.4	pIC50
ML337	Negative	6.23	pIC50
VU0463597	Negative	6.2	pIC50
L-glutamic acid	Agonist	5.4	pEC50
eGlu	Antagonist	5.4	pKi
(2R,3R)-APDC	Full agonist	5.3	pKi
compound 3 [PMID: 21105727]	Positive	5.1	pEC50
compound 4 [PMID: 21105727]	Positive	4.98	pEC50
compound 2 [PMID: 21105727]	Positive	4.9	pEC50
LY379268	Full agonist	4.8	pKi
(1S,3R)-ACPD	Full agonist	4.7	pKi
NAAG	Full agonist	4.7	pKi
(+)-MCPG	Antagonist	3.8	pKi

Binding affinities (BindingDB)

119 measured of 179 human assays (186 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[4-(4-butanoyl-3-hydroxy-2-methylphenoxy)butoxy]-3-methoxybenzoic acid	EC50	34 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[3-[(4-acetyl-3-hydroxy-2-methylphenoxy)methyl]phenyl]benzoic acid	EC50	35 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy]-3-methoxybenzoic acid	EC50	40 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]butoxy]-3-methoxybenzoic acid	EC50	47 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-(4-acetyl-3-hydroxy-2-methylphenoxy)butoxy]-3-methylbenzoic acid	EC50	50 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-(4-butanoyl-3-hydroxy-2-methylphenoxy)butoxy]-2-methylbenzoic acid	EC50	52 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-(3-hydroxy-2-methyl-4-propanoylphenoxy)butoxy]-2-methylbenzoic acid	EC50	62 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
5-[4-(4-butanoyl-3-hydroxy-2-methylphenoxy)butoxy]-2-fluorobenzoic acid	EC50	74 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-(3-hydroxy-2-methyl-4-propanoylphenoxy)butoxy]-3-methylbenzoic acid	EC50	82 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-chloro-4-[4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy]benzoic acid	EC50	96 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-fluoro-4-[4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy]benzoic acid	EC50	102 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-(4-butanoyl-3-hydroxy-2-methylphenoxy)butoxy]-4-methoxybenzoic acid	EC50	103 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-(4-butanoyl-3-hydroxy-2-methylphenoxy)butoxy]-3-methylbenzoic acid	EC50	104 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-[3-hydroxy-2-methyl-4-(2-methylpropanoyl)phenoxy]butoxy]-3-methoxybenzoic acid	EC50	113 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-(3-hydroxy-2-methyl-4-propanoylphenoxy)butoxy]-3-methoxybenzoic acid	EC50	114 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-[3-hydroxy-2-methyl-4-(2-methylpropanoyl)phenoxy]butoxy]-4-methoxybenzoic acid	EC50	116 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[3-[[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]methyl]phenyl]-4-methoxybenzoic acid	EC50	118 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy]benzoic acid	EC50	122 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
2-fluoro-5-[4-(3-hydroxy-2-methyl-4-propanoylphenoxy)butoxy]benzoic acid	EC50	124 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]butoxy]-2-methylbenzoic acid	EC50	136 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[3-[(4-butanoyl-3-hydroxy-2-methylphenoxy)methyl]phenyl]benzoic acid	EC50	142 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-[3-hydroxy-2-methyl-4-(2-methylpropanoyl)phenoxy]butoxy]-2-methylbenzoic acid	EC50	149 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
2-chloro-4-[4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy]benzoic acid	EC50	151 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
2-fluoro-5-[4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy]benzoic acid	EC50	153 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy]-4-methoxybenzoic acid	EC50	155 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[6-[[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]methyl]-2-pyridinyl]-4-methoxybenzoic acid	EC50	159 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-(4-acetyl-3-hydroxy-2-methylphenoxy)butoxy]-3-methoxybenzoic acid	EC50	161 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-(3-hydroxy-2-methyl-4-propanoylphenoxy)butoxy]-4-methoxybenzoic acid	EC50	162 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
2-fluoro-5-[4-[3-hydroxy-2-methyl-4-(2-methylpropanoyl)phenoxy]butoxy]benzoic acid	EC50	171 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy]-2-methylbenzoic acid	EC50	173 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[3-[[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]methyl]phenyl]benzoic acid	EC50	181 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]butoxy]-4-methoxybenzoic acid	EC50	184 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy]-2-methylbenzoic acid	EC50	192 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-(4-acetyl-3-hydroxy-2-methylphenoxy)butoxy]-2-methylbenzoic acid	EC50	200 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
5-[3-[[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]methyl]phenyl]-2-fluorobenzoic acid	EC50	208 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
5-[4-[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]butoxy]-2-fluorobenzoic acid	EC50	208 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[2-[[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]methyl]-4-pyridinyl]benzoic acid	EC50	209 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[3-[[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]methyl]phenyl]benzoic acid	EC50	219 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[3-[[3-hydroxy-2-methyl-4-(2-methylpropanoyl)phenoxy]methyl]phenyl]benzoic acid	EC50	222 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy]benzoic acid	EC50	222 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-[4-(2-cyclopentylacetyl)-3-hydroxy-2-methylphenoxy]butoxy]-3-methoxybenzoic acid	EC50	228 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-[[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]methyl]-2-pyridinyl]benzoic acid	EC50	230 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
5-[3-[[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]methyl]phenyl]-2-hydroxybenzoic acid	EC50	232 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[4-[3-hydroxy-2-methyl-4-(2-methylpropanoyl)phenoxy]butoxy]-3-methylbenzoic acid	EC50	234 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-chloro-4-[4-[4-(2-cyclopentylacetyl)-3-hydroxy-2-methylphenoxy]butoxy]benzoic acid	EC50	237 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
4-[[3-[[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]methyl]phenyl]methoxy]benzoic acid	EC50	238 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[4-[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]butoxy]-4-methoxy-N-methylsulfonylbenzamide	EC50	250 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
3-[6-[[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]methyl]-2-pyridinyl]benzenesulfonic acid	EC50	254 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
[4-[4-(4-acetyl-3-hydroxy-2-propylphenoxy)butoxy]-3-methylphenyl] formate	EC50	256 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
5-[4-(4-acetyl-3-hydroxy-2-methylphenoxy)butoxy]-2-fluorobenzoic acid	EC50	259 nM	US-10099993: Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof

ChEMBL bioactivities

315 potent at pChembl≥5 of 334 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.96	EC50	0.11	nM	CHEMBL2381640
9.77	Ki	0.17	nM	CHEMBL218710
9.77	EC50	0.17	nM	CHEMBL4068189
9.62	EC50	0.24	nM	CHEMBL2381652
9.33	Ki	0.47	nM	CHEMBL4071962
9.33	EC50	0.47	nM	CHEMBL4081453
9.15	EC50	0.71	nM	CHEMBL4091735
9.09	EC50	0.82	nM	CHEMBL4071962
9.03	Ki	0.927	nM	CHEMBL4081453
8.89	Ki	1.3	nM	CHEMBL432038
8.85	EC50	1.4	nM	CHEMBL218710
8.75	Ki	1.79	nM	CHEMBL4068189
8.70	EC50	2	nM	CHEMBL4091203
8.68	EC50	2.07	nM	CHEMBL121053
8.68	Ki	2.11	nM	CHEMBL4091203
8.67	EC50	2.12	nM	CHEMBL4070866
8.64	Ki	2.27	nM	CHEMBL4091735
8.64	Ki	2.29	nM	CHEMBL4095567
8.61	EC50	2.44	nM	CHEMBL4061162
8.60	Ki	2.5	nM	CHEMBL4751065
8.60	IC50	2.5	nM	CHEMBL4751065
8.57	Ki	2.7	nM	CHEMBL3969063
8.55	IC50	2.8	nM	CHEMBL432038
8.52	Ki	3	nM	CHEMBL140197
8.36	Ki	4.34	nM	CHEMBL4063336
8.36	IC50	4.35	nM	CHEMBL5797360
8.35	Ki	4.5	nM	CHEMBL186453
8.35	Ki	4.5	nM	CHEMBL4759992
8.34	EC50	4.58	nM	LY-379268
8.34	EC50	4.6	nM	LY-379268
8.34	Ki	4.56	nM	CHEMBL4061162
8.34	Ki	4.6	nM	LY-379268
8.33	Ki	4.7	nM	LY-389795
8.30	EC50	4.96	nM	CHEMBL4095995
8.30	EC50	4.96	nM	CHEMBL4098939
8.30	IC50	5.04	nM	CHEMBL5938305
8.29	EC50	5.1	nM	CHEMBL4090293
8.29	EC50	5.15	nM	CHEMBL4095567
8.24	Ki	5.8	nM	LY-379268
8.24	Ki	5.79	nM	CHEMBL4090293
8.23	Ki	5.9	nM	CHEMBL4780402
8.21	IC50	6.2	nM	CHEMBL4751065
8.20	IC50	6.3	nM	CHEMBL2381643
8.18	EC50	6.6	nM	CHEMBL2381643
8.18	EC50	6.6	nM	CHEMBL4063336
8.17	Ki	6.75	nM	CHEMBL4095995
8.17	Ki	6.8	nM	CHEMBL4776989
8.15	EC50	7.15	nM	CHEMBL4099470
8.12	EC50	7.6	nM	LY-389795
8.12	EC50	7.63	nM	LY-389795

PubChem BioAssay actives

304 with measured affinity, of 735 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(1S,2S,5R,6R)-2-amino-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748167: Agonist activity at human mGlu3 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by HTRF assay	ec50	0.0001	uM
(1R,4S,5S,6S)-4-amino-2-oxo-2lambda4-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid	275488: Displacement of [3H]LY341495 from human recombinant mGluR3 in RGT cells	ki	0.0002	uM
(1R,2S,4R,5R,6R)-2-amino-4-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748167: Agonist activity at human mGlu3 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by HTRF assay	ec50	0.0002	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(2-hydroxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468298: Agonist activity at human mGlu3 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	0.0002	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(3-chlorobenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468292: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in HEK cell membranes after 90 mins by liquid scintillation counting	ki	0.0005	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468298: Agonist activity at human mGlu3 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	0.0005	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(3-hydroxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468298: Agonist activity at human mGlu3 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	0.0007	uM
trans-(1S,2S)-2-[(1S)-1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]cyclopropane-1-carboxylic acid	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0013	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(3-fluorobenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468298: Agonist activity at human mGlu3 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	0.0020	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(4-hydroxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468298: Agonist activity at human mGlu3 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	0.0021	uM
(1R,2S,5S,6S)-2-amino-6-fluoro-4-oxobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	705390: Agonist activity at mGLUR3 expressed in CHO cells	ec50	0.0021	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(4-chlorobenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468292: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in HEK cell membranes after 90 mins by liquid scintillation counting	ki	0.0023	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(4-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468298: Agonist activity at human mGlu3 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	0.0024	uM
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0025	uM
(1R,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-dichlorophenyl)methoxy]-4-(1H-1,2,4-triazol-5-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1329918: Displacement of [3H]-LY459477 from human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing human EAAT1 after 90 mins by liquid scintillation counting method	ki	0.0027	uM
(1R,2S,3R)-2-[(S)-amino(carboxy)methyl]-3-hydroxycyclopropane-1-carboxylic acid	109322: Binding affinity towards metabotropic glutamate receptor 3 was determined	ki	0.0030	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(4-fluorobenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468292: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in HEK cell membranes after 90 mins by liquid scintillation counting	ki	0.0043	uM
(1R,2R,3R,4S,5R,6R)-2-amino-3-[(4-fluoro-3-methylphenyl)sulfanylmethyl]-4-(1H-1,2,4-triazol-5-ylsulfanyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0045	uM
(1R,2R,3R,5R,6R)-2-amino-3-[(3,4-dichlorophenyl)methoxy]-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	705386: Binding affinity to mGLUR3	ki	0.0045	uM
(1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid	109153: Inhibition of forskolin stimulated cAMP production in RGT cells expressing recombinant human Metabotropic glutamate receptor 3	ec50	0.0046	uM
(1R,4S,5S,6S)-4-amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid	109163: Ability to displace [3H]LY-341,495 from recombinant human Metabotropic glutamate receptor 3 expressed in RGT cells.	ki	0.0047	uM
(1S,2S,4S,5R,6S)-2-amino-4-benzamidobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468298: Agonist activity at human mGlu3 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	0.0050	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(2-chlorobenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468298: Agonist activity at human mGlu3 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	0.0050	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(2-fluorobenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468298: Agonist activity at human mGlu3 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	0.0051	uM
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(4-fluoro-3-methylphenyl)sulfanylmethyl]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0059	uM
(1S,2S,4S,5R,6R)-2-amino-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1714560: Agonist activity at mGlu3 (unknown origin)	ic50	0.0063	uM
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(4-fluorophenyl)sulfanylmethyl]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0068	uM
(1S,2S,4S,5R,6S)-2-amino-4-[(2-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468298: Agonist activity at human mGlu3 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	0.0072	uM
(4S,6S)-4-amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid	109164: Agonist potency against cloned Metabotropic glutamate receptor 3 (mGluR-3).	ki	0.0076	uM
(1S,2R,3R,4S,5R,6S)-4-acetamido-2-amino-3-[(4-fluoro-3-methylphenyl)sulfanylmethyl]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0077	uM
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-dichlorophenyl)sulfanylmethyl]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0094	uM
(1S,2S,4R,5R,6R)-2-amino-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1714560: Agonist activity at mGlu3 (unknown origin)	ic50	0.0112	uM
(1S,2S,4R,5R,6S)-2-amino-4-azidobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748167: Agonist activity at human mGlu3 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by HTRF assay	ec50	0.0123	uM
(1S,2R,3R,4S,5R,6S)-4-acetamido-2-amino-3-[(3,4-dichlorophenyl)methoxy]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1329854: Antagonist activity at recombinant human mGlu3 receptor expressed in hamster AV12 cells co-expressing human EAAT1 assessed as reduction of DCG-4-inhibited forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ic50	0.0143	uM
(1S,2S,5R,6S)-2-amino-4-methylidenebicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748167: Agonist activity at human mGlu3 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by HTRF assay	ec50	0.0155	uM
trans-(1S,2S)-2-[(1R)-1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]cyclopropane-1-carboxylic acid	109160: Ability to block 1S,3R-ACPD-induced inhibition of forskolin stimulated cyclic-AMP in non-neuronal cell line expressing human Metabotropic glutamate receptor 3	ic50	0.0160	uM
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-dichlorophenyl)methylsulfanylmethyl]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0163	uM
(1S,2R,3S,4S,5R,6R)-2-amino-4-hydroxy-3-(phenylsulfanylmethyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0192	uM
(1S,2R,3R,4S,5R,6S)-2-amino-3-[(3,4-dichlorophenyl)methoxy]-4-(methoxycarbonylamino)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1329854: Antagonist activity at recombinant human mGlu3 receptor expressed in hamster AV12 cells co-expressing human EAAT1 assessed as reduction of DCG-4-inhibited forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ic50	0.0205	uM
(1S,2S,4S,5R,6S)-2-amino-4-azidobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	748167: Agonist activity at human mGlu3 receptor expressed in golden Syrian hamster AV12 cells coexpressing EAAT1 after 20 mins by HTRF assay	ec50	0.0235	uM
(1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	109151: Agonistic activity against Human Metabotropic glutamate receptor 3	ec50	0.0243	uM
(1S,2S,4S,5R,6S)-2,4-diaminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1468298: Agonist activity at human mGlu3 receptor expressed in HEK cells assessed as inhibition of forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ec50	0.0249	uM
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(3-fluorophenyl)sulfanylmethyl]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0251	uM
(1S,2R,3S,4R,5R,6R)-2-amino-4-hydroxy-3-(phenylsulfanylmethyl)bicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0260	uM
(1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-dimethylphenyl)sulfanylmethyl]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid;hydrochloride	1714564: Displacement of [3H]-LY459477 from recombinant human mGlu3 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method	ki	0.0260	uM
(1R,2S,4S,5R,6R)-2-amino-4-[[5-(difluoromethyl)-1H-1,2,4-triazol-3-yl]sulfanyl]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1247522: Agonist activity at human recombinant mGlu3 receptor expressed in AV12 cells assessed as inhibition of forskolin-stimulated cAMP production after 1 hr by fluorescence assay	ec50	0.0273	uM
(1R,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-dichlorophenyl)methoxy]-4-[(2-methyl-1,2,4-triazol-3-yl)sulfanyl]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1329854: Antagonist activity at recombinant human mGlu3 receptor expressed in hamster AV12 cells co-expressing human EAAT1 assessed as reduction of DCG-4-inhibited forskolin-stimulated cAMP formation after 20 mins by HTRF assay	ic50	0.0296	uM
(1R,2S,4S,5R,6R)-2-amino-4-[[5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl]sulfanyl]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid	1247522: Agonist activity at human recombinant mGlu3 receptor expressed in AV12 cells assessed as inhibition of forskolin-stimulated cAMP production after 1 hr by fluorescence assay	ec50	0.0305	uM
(1S,2S,4S,5R,6S)-2-amino-4-methylbicyclo[3.1.0]hexane-2,6-dicarboxylic acid	246231: Evaluation of the functional effect on cAMP responses in RGT cells expressing human mGlu3 receptor	ec50	0.0340	uM
2-[(4-fluorophenoxy)methyl]-5-(4-fluorophenyl)-6,7-dihydropyrazolo[1,5-a]pyrazin-4-one	1268799: Antagonist activity at human mGlu3 expressed in HEK293 cells assessed as inhibition of glutamate-induced calcium mobilization	ec50	0.0340	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, increases expression, affects cotreatment	5
trichostatin A	affects cotreatment, decreases expression	3
bisphenol A	increases expression, affects cotreatment, increases methylation, decreases methylation	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Troglitazone	increases expression	1
Acetylcysteine	increases activity	1
Diphenylamine	affects response to substance	1
N-Nitrosopyrrolidine	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Fenofibrate	increases expression	1
Triclosan	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

ChEMBL screening assays

180 unique, capped per target: 102 functional, 76 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1013081	Binding	Binding affinity to human cloned mGluR3	Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid: a novel selective inhibitor of human excitatory amino acid transporter subtype 2. — J Med Chem
CHEMBL1027699	Functional	Antagonist activity at mGlu3 receptor	Discovery of molecular switches that modulate modes of metabotropic glutamate receptor subtype 5 (mGlu5) pharmacology in vitro and in vivo within a series of functionalized, regioisomeric 2- and 5-(phenylethynyl)pyrimidines. — J Med Chem
CHEMBL4620115	ADMET	Inhibition of human mGluR3 by FLIPR assay	Discovery of 4-arylquinoline-2-carboxamides, highly potent and selective class of mGluR2 negative allosteric modulators: From HTS to activity in animal models. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 2 spontaneously immortalized cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1T0	Abcam U-87MG GRM3 KO	Cancer cell line	Male
CVCL_KA80	CHO-K1/GRM3/Gqi5	Spontaneously immortalized cell line	Female
CVCL_KV33	cAMP Hunter CHO-K1 GRM3 Gi	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.