GPR18

gene

On this page

Also known as DRV2

Summary

GPR18 (G protein-coupled receptor 18, HGNC:4472) is a protein-coding gene on chromosome 13q32.3, encoding N-arachidonyl glycine receptor (Q14330). G protein-coupled receptor (GPCR) that plays a role in diverse physiological processes particularly within the immune and nervous systems.

Enables G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within T cell differentiation; negative regulation of leukocyte chemotaxis; and negative regulation of tumor necrosis factor production. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 2841 — RefSeq curated summary.

At a glance

GWAS associations: 4
Clinical variants (ClinVar): 49 total
Druggable target: yes — 2 molecules with ChEMBL bioactivity
MANE Select transcript: NM_001098200

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4472
Approved symbol	GPR18
Name	G protein-coupled receptor 18
Location	13q32.3
Locus type	gene with protein product
Status	Approved
Aliases	DRV2
Ensembl gene	ENSG00000125245
Ensembl biotype	protein_coding
OMIM	602042
Entrez	2841

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000340807, ENST00000397470, ENST00000397473, ENST00000416594, ENST00000678933

RefSeq mRNA: 2 — MANE Select: NM_001098200 NM_001098200, NM_005292

CCDS: CCDS9491

Canonical transcript exons

ENST00000397470 — 2 exons

Exon	Start	End
ENSE00001665647	99254739	99255906
ENSE00001666562	99258154	99258379

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 99.00.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1185 / max 162.0952, expressed in 223 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137985	1.9192	197
137984	0.1377	72
137986	0.0334	17
137983	0.0281	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.00	gold quality
male germ cell	CL:0000015	95.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.01	gold quality
lymph node	UBERON:0000029	87.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.32	gold quality
granulocyte	CL:0000094	85.61	gold quality
epithelium of nasopharynx	UBERON:0001951	84.71	gold quality
tonsil	UBERON:0002372	83.97	gold quality
blood	UBERON:0000178	82.97	gold quality
vermiform appendix	UBERON:0001154	82.93	gold quality
spleen	UBERON:0002106	79.30	gold quality
right testis	UBERON:0004534	79.23	gold quality
bone marrow	UBERON:0002371	79.18	gold quality
left testis	UBERON:0004533	78.68	gold quality
testis	UBERON:0000473	77.28	gold quality
caecum	UBERON:0001153	77.08	gold quality
leukocyte	CL:0000738	74.70	gold quality
colonic epithelium	UBERON:0000397	73.99	gold quality
monocyte	CL:0000576	73.61	gold quality
calcaneal tendon	UBERON:0003701	73.44	gold quality
mononuclear cell	CL:0000842	73.39	gold quality
ileal mucosa	UBERON:0000331	71.09	gold quality
jejunal mucosa	UBERON:0000399	71.08	gold quality
adrenal tissue	UBERON:0018303	69.19	gold quality
bone marrow cell	CL:0002092	68.90	gold quality
palpebral conjunctiva	UBERON:0001812	68.24	gold quality
tendon	UBERON:0000043	67.78	gold quality
superficial temporal artery	UBERON:0001614	65.83	gold quality
trabecular bone tissue	UBERON:0002483	64.09	gold quality
thymus	UBERON:0002370	63.59	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting GPR18, 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-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-1244	99.33	68.38	832
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-4475	97.36	66.95	761

Literature-anchored findings (GeneRIF, showing 11)

N-arachidonylglycine is a natural ligand for GPR18 (PMID:16844083)
GPR18, the most abundantly overexpressed orphan G-protein-coupled receptor in all melanoma metastases, is constitutively active and inhibits apoptosis, indicating an important role for GPR18 in tumor cell survival. (PMID:20880198)
REVIEW: functional properties and in vivo biology (PMID:21261596)
the results presented herein provide further evidence for GPR18 as a candidate cannabinoid receptor (PMID:24762058)
A novel RvD2-GPR18 resolution axis stimulates human and mouse phagocyte functions to control bacterial infections and promote organ protection. (PMID:26195725)
Results indicate that G protein-coupled receptor 18 (GPR18) might be involved in physiological processes of spermatozoa, suggesting GPR18 to be a potential player in sperm physiology. (PMID:27572937)
GPR18 interacts with cannabinoid CB2 but not with CB1 receptors. (PMID:29870711)
Lipopolysaccharides-Toll-like receptor (TLR)4 signaling mediated the GPR18 expression on polymorphonuclear neutrophils. These results indicate that decreased percentage GPR18-positive polymorphonuclear neutrophils is associated with increased severity and poorer outcome of sepsis. (PMID:30503722)
molecular dynamics simulations of wild-type (WT) GPR18 and the A3.39N mutant in fully hydrated (POPC) phophatidylcholine lipid bilayers, are reported. (PMID:31075933)
Novel selective agonist of GPR18, PSB-KK-1415 exerts potent anti-inflammatory and anti-nociceptive activities in animal models of intestinal inflammation and inflammatory pain. (PMID:33058313)
The resolvin D2 - GPR18 axis is expressed in human coronary atherosclerosis and transduces atheroprotection in apolipoprotein E deficient mice. (PMID:35525326)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpr18	ENSDARG00000062009
mus_musculus	Gpr18	ENSMUSG00000050350
rattus_norvegicus	Gpr18	ENSRNOG00000012628
caenorhabditis_elegans		WBGENE00016570

Paralogs (16): P2RY10 (ENSG00000078589), F2RL3 (ENSG00000127533), GPR55 (ENSG00000135898), LPAR6 (ENSG00000139679), GPR65 (ENSG00000140030), GPR17 (ENSG00000144230), LPAR4 (ENSG00000147145), CYSLTR2 (ENSG00000152207), F2RL2 (ENSG00000164220), F2RL1 (ENSG00000164251), CYSLTR1 (ENSG00000173198), GPR4 (ENSG00000177464), GPR35 (ENSG00000178623), F2R (ENSG00000181104), P2RY8 (ENSG00000182162), GPR20 (ENSG00000204882)

Protein

Protein identifiers

N-arachidonyl glycine receptor — Q14330 (reviewed: Q14330)

Alternative names: G-protein coupled receptor 18

All UniProt accessions (3): Q14330, H9NIM1, Q5JUH9

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor (GPCR) that plays a role in diverse physiological processes particularly within the immune and nervous systems. Becomes active when triggered by various endogenous ligands including endocannabinoid N-arachidonyl glycine (NAGly), delta-9-tetrahydrocannabinol or resolvin D2/RvD2 derived from the omega-3 fatty acid docosahexaenoic acid (DHA). Upon RvD2 binding, facilitates the resolution of inflammation, aiding in tissue repair and homeostasis. Mechanistically, RvD2 ligation initiates Galphas protein coupling, activation of cAMP-PKA signaling pathway and phosphorylation of STAT3, leading to RvD2-stimulated macrophage phagocytosis. Mediates NAGly-induced process of reorganization of actin filaments and induction of acrosomal exocytosis. Activation by N-arachidonoyl glycine (NAGly) can also induce apoptosis in macrophages. Plays a role in homeostasis of CD8+ subsets of intraepithelial lymphocytes (IELs) (CD8alphaalpha and CD8alphabeta IELs) in small intestine by supporting preferential migration of CD8alphaalpha T-cells to intraepithelial compartment over lamina propria compartment, and by mediating their reconstitution into small intestine after bone marrow transplant. Also participates in hypotensive responses, mediating reduction in intraocular and blood pressure.

Subcellular location. Cell membrane. Cytoplasmic vesicle membrane.

Tissue specificity. Expressed in midpiece of spermatozoon (at protein level). Most abundant in testis and spleen. Highly expressed in CD4 and CD8-positive T-cells as well as CD19-positive B-cells.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (2): NP_001091670, NP_005283 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR028335	GPR18	Family

Pfam: PF00001

UniProt features (27 total): topological domain 8, transmembrane region 7, sequence conflict 7, chain 1, modified residue 1, glycosylation site 1, disulfide bond 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14330-F1	86.49	0.60

Functional residue map

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

Post-translational modifications (1): 322

Disulfide bonds (1): 94–172

Glycosylation sites (1): 14

Mutagenesis-validated functional residues (1):

Position	Phenotype
108	increased cell surface expression.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 289 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, WALLACE_PROSTATE_CANCER_RACE_UP, MORF_MSH3, GOBP_CELL_CHEMOTAXIS, MODULE_571, MORF_BRCA1, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, FOXO4_01, FOXO1_01, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, MORF_RAD51L3, GOBP_LEUKOCYTE_CHEMOTAXIS, PUJANA_CHEK2_PCC_NETWORK, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION

GO Biological Process (8): CD8-positive, alpha-beta intraepithelial T cell differentiation (GO:0002300), CD8-positive, gamma-delta intraepithelial T cell differentiation (GO:0002305), negative regulation of leukocyte chemotaxis (GO:0002689), G protein-coupled receptor signaling pathway (GO:0007186), negative regulation of tumor necrosis factor production (GO:0032720), signal transduction (GO:0007165), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), positive regulation of phagocytosis (GO:0050766)

GO Molecular Function (1): G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (4): plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR ligand binding	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
alpha-beta intraepithelial T cell differentiation	1
CD8-positive, alpha-beta T cell differentiation	1
gamma-delta intraepithelial T cell differentiation	1
negative regulation of leukocyte migration	1
regulation of leukocyte chemotaxis	1
leukocyte chemotaxis	1
negative regulation of chemotaxis	1
G protein-coupled receptor activity	1
signal transduction	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
phagocytosis	1
positive regulation of endocytosis	1
regulation of phagocytosis	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
membrane	1
cell periphery	1
cellular anatomical structure	1
vesicle membrane	1
cytoplasmic vesicle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1138 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPR18	GPR119	Q8TDV5	866
GPR18	TRPV1	Q8NER1	787
GPR18	FAAH	O00519	736
GPR18	GPR3	P46089	716
GPR18	TRPM8	Q7Z2W7	671
GPR18	GPR12	P47775	658
GPR18	CNR1	P21554	644
GPR18	GPR6	P46095	635
GPR18	LGR6	Q9HBX8	628
GPR18	NAPEPLD	Q6IQ20	602
GPR18	MGLL	Q99685	593
GPR18	GFER	P55789	590
GPR18	TRPV2	Q9Y5S1	584
GPR18	ABHD12	Q8N2K0	578
GPR18	ABHD6	Q9BV23	577

IntAct

9 interactions, top by confidence:

A	B	Type	Score
RAMP1	GPR18	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	GPR18	psi-mi:“MI:0915”(physical association)	0.400
GPR18	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
GPR18	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
CNR2	GPR18	psi-mi:“MI:2364”(proximity)	0.380
CNR2	GPR18	psi-mi:“MI:0403”(colocalization)	0.380
GPR18	ARG1	psi-mi:“MI:0914”(association)	0.350
GPR18	FLG	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): CALML5 (Affinity Capture-MS), SERPINB5 (Affinity Capture-MS), CALML3 (Affinity Capture-MS), ARG1 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), POF1B (Affinity Capture-MS), FLG (Affinity Capture-MS), CPA4 (Affinity Capture-MS), HAL (Affinity Capture-MS), ALDH3A1 (Affinity Capture-MS), NCCRP1 (Affinity Capture-MS), SERPINB5 (Affinity Capture-MS), HAL (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS)

ESM2 similar proteins: A1A5S3, A5PLE7, B0UXR0, B5X337, F5HDK1, F5HF62, F8VQN3, O00421, O18982, O97663, P09703, P32249, P35351, P35374, P46002, P49685, P50052, P51676, P56412, P69332, P69333, Q01035, Q0II78, Q0VDU3, Q14330, Q1RMI1, Q28929, Q3T0E9, Q3U507, Q4R613, Q6IYF9, Q75ZH0, Q83207, Q89609, Q8BZR0, Q8IYL9, Q8K1Z6, Q95N03, Q96P67, Q98146

Diamond homologs: A1A5S3, E9QJ73, O08707, P29755, P32248, P33396, P49220, P79785, P97266, Q14330, Q149R9, Q16581, Q28553, Q3T0E9, Q3ZC80, Q4R613, Q58D85, Q5REI5, Q6IYF8, Q6TAC8, Q6Y1R5, Q8K1Z6, Q8NGA4, Q8VIH9, Q920E1, Q924T8, Q95N02, Q96P68, Q99PE3, Q9H1C0, A7YY44, B0UXR0, B4XF06, O00254, O08675, O35811, O43193, O77408, O88634, P20789

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

475 predictions. Top by Δscore:

Variant	Effect	Δscore
13:99255907:C:CC	acceptor_gain	1.0000
13:99258148:GCTTA:G	donor_loss	1.0000
13:99258149:CTTA:C	donor_loss	1.0000
13:99258150:TTACC:T	donor_loss	1.0000
13:99258151:TACCT:T	donor_loss	1.0000
13:99258152:ACCT:A	donor_gain	1.0000
13:99258153:CCTC:C	donor_gain	1.0000
13:99258155:T:TA	donor_gain	1.0000
13:99255903:GAAA:G	acceptor_gain	0.9900
13:99258152:A:AC	donor_gain	0.9900
13:99258153:C:CC	donor_gain	0.9900
13:99258153:CCT:C	donor_gain	0.9900
13:99255905:AA:A	acceptor_gain	0.9800
13:99255906:ACTG:A	acceptor_loss	0.9800
13:99255907:C:CA	acceptor_loss	0.9800
13:99256454:AAAG:A	donor_gain	0.9800
13:99255909:G:C	acceptor_gain	0.9700
13:99255919:T:C	acceptor_gain	0.9700
13:99255919:T:TC	acceptor_gain	0.9700
13:99255299:GTCGA:G	donor_gain	0.9600
13:99255904:AAA:A	acceptor_gain	0.9600
13:99255294:T:G	donor_gain	0.9500
13:99255297:C:A	donor_gain	0.9500
13:99258152:ACCTC:A	donor_gain	0.9500
13:99258153:CCTCC:C	donor_gain	0.9500
13:99255103:AGCAT:A	acceptor_gain	0.9400
13:99255902:AGAAA:A	acceptor_gain	0.9400
13:99254905:A:AG	acceptor_gain	0.9300
13:99254906:G:GG	acceptor_gain	0.9300
13:99255915:A:C	acceptor_gain	0.9200

AlphaMissense

2185 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:99255525:A:C	S116R	0.998
13:99255525:A:T	S116R	0.998
13:99255527:T:G	S116R	0.998
13:99255612:C:A	W87C	0.998
13:99255612:C:G	W87C	0.998
13:99255133:G:C	P247R	0.997
13:99255133:G:T	P247H	0.996
13:99255437:A:G	W146R	0.996
13:99255437:A:T	W146R	0.996
13:99255614:A:G	W87R	0.996
13:99255614:A:T	W87R	0.996
13:99255767:C:G	G36R	0.996
13:99255767:C:T	G36R	0.996
13:99255039:G:C	S278R	0.995
13:99255039:G:T	S278R	0.995
13:99255041:T:G	S278R	0.995
13:99255143:A:G	C244R	0.995
13:99255766:C:T	G36E	0.995
13:99254994:A:C	F293L	0.993
13:99254994:A:T	F293L	0.993
13:99254996:A:G	F293L	0.993
13:99255138:A:C	F245L	0.993
13:99255138:A:T	F245L	0.993
13:99255140:A:G	F245L	0.993
13:99255277:G:C	P199R	0.993
13:99255592:C:G	C94S	0.992
13:99255593:A:T	C94S	0.992
13:99255646:G:C	P76R	0.992
13:99255277:G:T	P199H	0.991
13:99255545:A:G	W110R	0.991

dbSNP variants (sampled 300 via entrez): RS1000090102 (13:99257979 A>C,G), RS1001014867 (13:99259153 G>A), RS1001124325 (13:99256806 T>C), RS1001503475 (13:99255925 A>G), RS1001760600 (13:99256574 C>T), RS1001788253 (13:99257952 A>G), RS1001840450 (13:99257481 T>C), RS1002470610 (13:99254653 A>G), RS1002833847 (13:99255153 C>A,G,T), RS1003951480 (13:99257843 C>T), RS1004013686 (13:99255009 G>A), RS1004406851 (13:99257403 T>A), RS1005077383 (13:99256864 G>A,C,T), RS1005454399 (13:99256679 G>A), RS1006703536 (13:99256267 G>A,T)

Disease associations

OMIM: gene MIM:602042 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001725_21	Inflammatory bowel disease	2.000000e-14
GCST004131_117	Inflammatory bowel disease	1.000000e-06
GCST008916_6	Asthma	4.000000e-13
GCST009798_86	Asthma	3.000000e-16

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2384898 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 77,833 (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
CHEMBL111	RIMONABANT	4	15,726
CHEMBL465	DRONABINOL	4	62,107

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — GPR18, GPR55 and GPR119

Most potent curated ligand interactions (10 total), top 10:

Ligand	Action	Affinity	Parameter
PSB-KK1415	Agonist	7.72	pEC50
PSB-KK1445	Agonist	7.34	pEC50
O-1602	Agonist	7.19	pEC50
PSB-KD107	Agonist	6.25	pEC50
abnormal cannabidiol	Agonist	6.08	pEC50
Δ⁹-tetrahydrocannabinol	Full agonist	6.02	pEC50
anandamide	Full agonist	5.42	pEC50
arachidonylcyclopropylamide	Agonist	4.87	pEC50
cannabidiol	Partial agonist	4.29	pEC50
AM251	Partial agonist	4.02	pEC50

ChEMBL bioactivities

97 potent at pChembl≥5 of 106 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.00	EC50	10	nM	CHEMBL5517636
7.72	EC50	19	nM	CHEMBL5556102
7.70	EC50	20	nM	ARACHIDONOYL GLYCINE
7.62	EC50	24	nM	CHEMBL5557729
7.42	EC50	38	nM	CHEMBL5556102
7.38	EC50	42	nM	CHEMBL5556617
7.36	EC50	44	nM	ARACHIDONOYL GLYCINE
7.27	EC50	54	nM	CHEMBL5558124
7.22	EC50	60	nM	CHEMBL5556677
7.19	EC50	64	nM	CHEMBL5532256
7.15	EC50	71	nM	CHEMBL5512594
7.14	EC50	72	nM	CHEMBL5555231
7.13	EC50	74	nM	CHEMBL5523402
7.10	EC50	80	nM	CHEMBL5532000
7.02	EC50	95	nM	CHEMBL5557906
6.99	EC50	102	nM	CHEMBL5556346
6.96	EC50	111	nM	CHEMBL5558903
6.94	EC50	115	nM	CHEMBL5542310
6.92	EC50	120	nM	CHEMBL5556049
6.87	EC50	136	nM	CHEMBL5549936
6.86	EC50	137	nM	CHEMBL5557995
6.86	EC50	138	nM	CHEMBL5557393
6.85	EC50	142	nM	CHEMBL5557839
6.83	EC50	149	nM	CHEMBL5505829
6.82	EC50	151	nM	CHEMBL5558263
6.78	EC50	166	nM	CHEMBL5523442
6.77	EC50	169	nM	CHEMBL5505898
6.72	EC50	190	nM	CHEMBL5517700
6.72	EC50	189	nM	CHEMBL5555055
6.71	EC50	196	nM	CHEMBL5517653
6.71	EC50	193	nM	CHEMBL5555914
6.69	EC50	206	nM	CHEMBL5556551
6.66	EC50	218	nM	CHEMBL5557780
6.64	EC50	229	nM	CHEMBL5558536
6.62	IC50	238	nM	CHEMBL4174825
6.61	EC50	247	nM	CHEMBL5523497
6.59	EC50	254	nM	CHEMBL5505756
6.58	EC50	261	nM	CHEMBL5559512
6.55	IC50	279	nM	CHEMBL3221188
6.46	EC50	347	nM	CHEMBL5527882
6.46	EC50	351	nM	CHEMBL5556254
6.45	EC50	352	nM	CHEMBL5542965
6.38	EC50	417	nM	CHEMBL5558126
6.36	EC50	442	nM	CHEMBL5559109
6.34	EC50	454	nM	CHEMBL4758188
6.33	EC50	469	nM	CHEMBL5557185
6.31	EC50	486	nM	CHEMBL5523663
6.31	IC50	487	nM	CHEMBL4168457
6.25	EC50	562	nM	CHEMBL239232
6.23	EC50	584	nM	CHEMBL5556620

PubChem BioAssay actives

81 with measured affinity, of 515 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
7-[(3-bromophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0100	uM
7-[(4-chlorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0190	uM
2-[[(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoyl]amino]acetic acid	1360829: Agonist activity at recombinant full length human GPR18 expressed in CHO cells assessed as forskolin-stimulated cAMP accumulation after 10 mins by enzyme immunoassay	ec50	0.0200	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-7-[(4-methylphenyl)methyl]purine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0240	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-7-[(4-nitrophenyl)methyl]purine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0420	uM
7-[(4-fluorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0540	uM
7-[(2-chlorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0600	uM
7-[(2,4-dichlorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0640	uM
7-[(3-chlorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0710	uM
7-[(4-bromophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0720	uM
7-[(3,4-dichlorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0740	uM
7-[(4-chloro-3-fluorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0800	uM
7-[(4-chlorophenyl)methyl]-3-ethyl-8-[2-(1H-indol-3-yl)ethylamino]-1-methylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.0950	uM
7-(2-cyclohexylethyl)-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1020	uM
7-but-3-enyl-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1110	uM
7-[(3-fluorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1150	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-7-(3-phenylpropyl)purine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1200	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-7-[[4-(trifluoromethyl)phenyl]methyl]purine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1360	uM
7-[(2-fluorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1370	uM
8-[2-(1H-indol-3-yl)ethylamino]-7-[(4-methoxyphenyl)methyl]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1380	uM
7-[(3,4-difluorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1420	uM
7-benzyl-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1490	uM
7-butyl-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1510	uM
8-[2-(1H-indol-3-yl)ethylamino]-7-[(3-methoxyphenyl)methyl]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1660	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-7-prop-2-enylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1690	uM
7-[(2-bromophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1890	uM
7-ethyl-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1900	uM
7-[(3-chloro-4-fluorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1930	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-7-propylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.1960	uM
7-[(4-chlorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1-methyl-3H-purine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.2060	uM
N-[4-[[8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-2,6-dioxopurin-7-yl]methyl]phenyl]acetamide	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.2180	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-7-(2-phenoxyethyl)purine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.2290	uM
(2Z)-2-[[3-[6-(4-methylphenoxy)hexoxy]phenyl]methylidene]-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-3-one	1360822: Antagonist activity at recombinant human GPR18 expressed in CHO cells assessed as inhibition of delta9-THC-induced beta-arrestin recruitment preincubated for 60 mins followed by delta9-THC addition for 90 mins measured for 1 sec by luminescence assay	ic50	0.2380	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-7-prop-2-ynylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.2470	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-7-pent-2-ynylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.2540	uM
7-[(4-aminophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.2610	uM
7-[(2,6-dichlorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.3470	uM
7-[(4-chlorophenyl)methyl]-3-(2-fluoroethyl)-8-[2-(1H-indol-3-yl)ethylamino]-1-methylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.3510	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-7-[(4-propan-2-ylphenyl)methyl]purine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.3520	uM
7-[2-(4-chlorophenoxy)ethyl]-8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.4170	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-7-(2-phenylethyl)purine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.4420	uM
10-[2-(1H-indol-3-yl)ethyl]-1,3-dimethyl-6,7,8,9-tetrahydropurino[7,8-a][1,3]diazepine-2,4-dione	1725628: Agonist activity at Prolink1-tagged human GPR18 receptor expressed in CHO cells assessed as induction of beta-arrestin recruitment after 90 mins by beta-galactosidase based topcount luminescence analysis	ec50	0.4540	uM
methyl 4-[[8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-2,6-dioxopurin-7-yl]methyl]benzoate	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.4690	uM
7-[(4-chlorophenyl)methyl]-8-[2-(1H-indol-3-yl)ethylamino]-1-methyl-3-(2,2,2-trifluoroethyl)purine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.4860	uM
(2Z)-2-[[3-[6-(4-chlorophenoxy)hexoxy]phenyl]methylidene]-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-3-one	2065434: Antagonist activity at human GPR18 receptor expressed in CHO cells assessed as inhibition of THC-induced activation by measuring beta-arrestin2 recruitment	ic50	0.4870	uM
9-[2-(1H-indol-3-yl)ethyl]-1,3-dimethyl-7,8-dihydro-6H-purino[7,8-a]pyrimidine-2,4-dione	1725628: Agonist activity at Prolink1-tagged human GPR18 receptor expressed in CHO cells assessed as induction of beta-arrestin recruitment after 90 mins by beta-galactosidase based topcount luminescence analysis	ec50	0.5620	uM
4-[[8-[2-(1H-indol-3-yl)ethylamino]-1,3-dimethyl-2,6-dioxopurin-7-yl]methyl]-N-propylbenzenesulfonamide	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.5840	uM
8-[2-(1H-indol-3-yl)ethylamino]-1,3,7-trimethylpurine-2,6-dione	2065411: Agonist activity at human GPR18 expressed in CHO cells assessed as activation by measuring beta-arrestin2 recruitment incubated for 90 mins by luminescence based assay	ec50	0.9020	uM
(2Z)-2-[[3-[5-(4-chlorophenoxy)pentoxy]phenyl]methylidene]-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-3-one	1360822: Antagonist activity at recombinant human GPR18 expressed in CHO cells assessed as inhibition of delta9-THC-induced beta-arrestin recruitment preincubated for 60 mins followed by delta9-THC addition for 90 mins measured for 1 sec by luminescence assay	ic50	1.1400	uM
(2Z)-2-[[3-[8-(4-chlorophenoxy)octoxy]phenyl]methylidene]-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazin-3-one	1360822: Antagonist activity at recombinant human GPR18 expressed in CHO cells assessed as inhibition of delta9-THC-induced beta-arrestin recruitment preincubated for 60 mins followed by delta9-THC addition for 90 mins measured for 1 sec by luminescence assay	ic50	1.1500	uM

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	increases expression	3
3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol	affects binding, decreases activity, decreases reaction, increases activity	2
Hexachlorocyclohexane	increases expression	2
Benzo(a)pyrene	decreases expression, increases expression	2
Nickel	increases expression	2
Dronabinol	affects binding, decreases reaction, increases activity	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
beauvericin	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
ochratoxin A	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
gardenoside	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3-dichloro-1-propanol	increases expression	1
CGP 52608	affects binding, increases reaction	1
enniatins	affects cotreatment, decreases expression	1
chlorantranilipole	increases expression	1
(+)-JQ1 compound	decreases expression	1
Cyclophosphamide	decreases expression	1
Chlorpyrifos	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Methylmercury Compounds	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

39 unique, capped per target: 22 binding, 17 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2388873	Binding	Agonist activity at human GPR18 transfected in CHO cells after 90 mins by beta-arrestin translocation assay	Antagonists for the orphan G-protein-coupled receptor GPR55 based on a coumarin scaffold. — J Med Chem
CHEMBL4155949	Functional	Antagonist activity at recombinant human GPR18 expressed in CHO cells assessed as inhibition of delta9-THC-induced beta-arrestin recruitment preincubated for 60 mins followed by delta9-THC addition for 90 mins measured for 1 sec by luminesc	Structure-activity relationships of imidazothiazinones and analogs as antagonists of the cannabinoid-activated orphan G protein-coupled receptor GPR18. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KX49	PathHunter CHO-K1 GPR18 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Targeted by drugs: Cannabidiol, Dronabinol, Nabiximols