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CNR2

gene
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Also known as CB2

Summary

CNR2 (cannabinoid receptor 2, HGNC:2160) is a protein-coding gene on chromosome 1p36.11, encoding Cannabinoid receptor 2 (P34972). Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase.

The cannabinoid delta-9-tetrahydrocannabinol is the principal psychoactive ingredient of marijuana. The proteins encoded by this gene and the cannabinoid receptor 1 (brain) (CNR1) gene have the characteristics of a guanine nucleotide-binding protein (G-protein)-coupled receptor for cannabinoids. They inhibit adenylate cyclase activity in a dose-dependent, stereoselective, and pertussis toxin-sensitive manner. These proteins have been found to be involved in the cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana. The cannabinoid receptors are members of family 1 of the G-protein-coupled receptors.

Source: NCBI Gene 1269 — RefSeq curated summary.

At a glance

  • GWAS associations: 10
  • Clinical variants (ClinVar): 55 total
  • Druggable target: yes — 27 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_001841

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:2160
Approved symbolCNR2
Namecannabinoid receptor 2
Location1p36.11
Locus typegene with protein product
StatusApproved
AliasesCB2
Ensembl geneENSG00000188822
Ensembl biotypeprotein_coding
OMIM605051
Entrez1269

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000374472

RefSeq mRNA: 1 — MANE Select: NM_001841 NM_001841

CCDS: CCDS245

Canonical transcript exons

ENST00000374472 — 2 exons

ExonStartEnd
ENSE000014636092387051523875662
ENSE000014636112391324623913362

Expression profiles

Bgee: expression breadth broad, 52 present calls, max score 75.71.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.5950 / max 138.9011, expressed in 153 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter IDTPM avgSamples expressed
110161.2748127
110180.188880
110170.089752
110190.028512
110200.01324

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
spleenUBERON:000210675.71gold quality
lymph nodeUBERON:000002975.51gold quality
triceps brachiiUBERON:000150974.97gold quality
gluteal muscleUBERON:000200074.97gold quality
spermCL:000001974.82gold quality
tibialis anteriorUBERON:000138574.62silver quality
male germ cellCL:000001574.15gold quality
ileal mucosaUBERON:000033172.18gold quality
diaphragmUBERON:000110371.44gold quality
granulocyteCL:000009471.17gold quality
hair follicleUBERON:000207368.62gold quality
deltoidUBERON:000147667.08silver quality
superficial temporal arteryUBERON:000161465.86gold quality
cervix squamous epitheliumUBERON:000692265.21gold quality
olfactory bulbUBERON:000226464.89gold quality
type B pancreatic cellCL:000016964.76gold quality
bloodUBERON:000017864.45gold quality
deciduaUBERON:000245064.31gold quality
mucosa of urinary bladderUBERON:000125964.27gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450264.00gold quality
Brodmann (1909) area 46UBERON:000648363.73gold quality
caecumUBERON:000115363.69gold quality
pancreatic ductal cellCL:000207963.59silver quality
vermiform appendixUBERON:000115463.54gold quality
thymusUBERON:000237063.47gold quality
esophagus squamous epitheliumUBERON:000692062.79gold quality
quadriceps femorisUBERON:000137762.77gold quality
superior surface of tongueUBERON:000737162.70silver quality
upper arm skinUBERON:000426362.19gold quality
epithelial cell of pancreasCL:000008362.06gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes12.66
E-ENAD-27no3.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting CNR2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-7110-3P100.0073.182486
HSA-MIR-545-3P99.9570.742783
HSA-MIR-1236-3P99.9468.041695
HSA-MIR-4766-5P99.7569.232662
HSA-MIR-569399.2466.671106
HSA-MIR-319999.1765.19696
HSA-MIR-805299.1765.01719
HSA-MIR-146A-3P99.1368.991881
HSA-MIR-6809-5P99.1368.451223
HSA-MIR-29B-1-5P98.8668.351364
HSA-MIR-518C-5P98.5369.201640
HSA-MIR-1910-3P98.4467.511695
HSA-MIR-6511A-5P98.1367.471770
HSA-MIR-607298.0066.47804
HSA-MIR-7113-5P97.8867.331735
HSA-MIR-10526-3P97.8664.971342
HSA-MIR-366197.8367.30705
HSA-MIR-66597.6065.641781
HSA-MIR-63197.0566.93602
HSA-MIR-6891-3P95.8065.76683
HSA-MIR-433095.4466.39993

Literature-anchored findings (GeneRIF, showing 40)

  • CB1 and CB2 receptor mRNA expression in human peripheral blood mononuclear cells (PBMC) from various donor types. (PMID:11727770)
  • dendritic cells were also found to express measurable amounts of CB1 and CB2 receptors and of FAAH. Cell maturation did not consistently modify the expression of these proteins (PMID:12153574)
  • Absence of a conserved proline and presence of a conserved tyrosine in the CB2 cannabinoid receptor are crucial for its function. (PMID:12417328)
  • CB2 plays a role in inhibiting neovascularization and skin neoplasm development (PMID:12511587)
  • Effects of D3.49A, R3.50A, and A6.34E mutations on ligand binding and activation of the cannabinoid-2 (CB2) receptor. (PMID:12663043)
  • 2-arachidonoylglycerol induces the migration of several types of leukocytes such as macrophages/monocytes through a CB2 receptor-dependent mechanism thereby stimulating inflammatory reactions and immune responses (PMID:12711605)
  • analysis of human acute myeloid leukemia (AML) samples revealed the presence of CB2 mRNA transcripts in several cases. (PMID:12799277)
  • In hippocampus and entorhinal cortex of Alzheimer’s disease patients both fatty acid amide hydrolase and cannabinoid CB2 receptors are abundantly and selectively expressed in neuritic plaque-associated astrocytes and microglia (PMID:14657172)
  • A critical role is indicated for CB2 in migration of B cells and the lymphoid germinal center response. (PMID:14764676)
  • delta(9)-THC induces an influx of extracellular calcium in resting T cells in a CB1- CB2- -dependent manner (PMID:14966196)
  • aberrantly expressed in a high percentage of human acute myeloid leukemias (PMID:15039279)
  • CB2 receptors are present in a specific microglial cell type of the human cerebellum, namely, perivascular microglial cells. (PMID:15266552)
  • proposition that 2-AG (2-arachidonoylglycerol) is the true natural ligand for both the CB1 and CB2 receptors (PMID:15456404)
  • The immune system-associated cannabinoid CB2 receptors were localized only to placental macrophages (PMID:15472222)
  • Senile plaques in AD patients express CB2 receptors which show increased nitration. (PMID:15728830)
  • CB2 receptors highly up-regulated in cirrhotic liver, predominantly in hepatic fibrogenic cells. Antifibrogenic role of CB2 receptors during chronic liver injury. (PMID:15765409)
  • Collectively, these results demonstrate reduced endogenous fatty acid amide immunomodulatory responses in individuals with the CB2 188-189 GG/GG genotype and suggest that this CB2 gene variation may be a risk factor for autoimmunity. (PMID:15845647)
  • CB1 and CB2 immunoreactivity was observed in cutaneous nerve fiber bundles, mast cells, macrophages, epidermal keratinocytes, and the epithelial cells of hair follicles, sebocytes and eccrine sweat glands. (PMID:15927811)
  • Data support a role for p38 MAPK in cannabinoid receptor 2-induced apoptosis of human leukaemia cells. (PMID:16139274)
  • A role is demonstrated for the peripherally expressed CB2 receptor in the etiology of osteoporosis, whereas no convincing association is found for cannabinoid receptor type 1 (Cnr1). (PMID:16204352)
  • Results describe the modification of 12-phenylacetyl-ricinoleoyl-vanillamide and its activity at TRPV1 and CB2 receptors. (PMID:16406364)
  • CB(2) receptors are involved in cannabinoid-mediated inhibition of the chemokine CXCL12-induced and CXCR4-mediated chemotaxis of Jurkat T cells and their transendothelial migration. (PMID:16503355)
  • CB2 might play a role in regulating excessive inflammatory response by controlling RhoA activation, thereby suppressing neutrophil migration (PMID:16513651)
  • analysis of cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects of alkylamides from Echinacea (PMID:16547349)
  • These data strongly suggest that AM1241 produces antinociception in vivo by activating CB2 cannabinoid receptors. (PMID:16563625)
  • Results presented here show that CB2 receptor activation signals apoptosis via a ceramide-dependent stimulation of the mitochondrial intrinsic pathway. (PMID:16624285)
  • lipid rafts control CB1R, but not CB2R, and endocannabinoid transport in immune and neuronal cells. (PMID:17015679)
  • apoptosis induced by cannabinoid receptor CB1 and CB2 agonists leads to activation of ERK1/2 leading to G1 cell cycle arrest in prostate cancer cells (PMID:17068343)
  • High expression of CB2 receptor was observed in 33 (52%) hepatocellular carcinoma. (PMID:17074588)
  • There is an association between the Q63R polymorphism of the CB2 gene and alcoholism in a Japanese population. (PMID:17189959)
  • We tested if cannabinoid type 2 receptor (CB2) in the central nervous system plays a role in alcohol abuse/dependence in animal model and then examined an association between the CB2 gene polymorphism and alcoholism in human. (PMID:17189959)
  • Dual affinity tags were used for the expression and purification of functional CNR2. (PMID:17223358)
  • Activation of CB2 cannabinoid receptors by JWH133 protects against I/R damage by decreasing inflammatory cell infiltration, tissue and serum TNF-alpha, MIP-1alpha and MIP-2 levels, tissue lipid peroxidation, and expression of ICAM-1 in vivo (PMID:17327359)
  • polymorphisms of CNR2 may confer susceptibility to postmenopausal osteoporosis in women, and that of GJA4 to osteoporosis in men (PMID:17390085)
  • abundant levels of CB2 protein were present on T-NHL and in many B-NHL. NHL specimens in general stained positively with both C-terminal specific anti-CB2 and N-terminal specific CB2 antibody (PMID:17613768)
  • CB2 receptor agonists attenuated TNF signaling in inflammation models. (PMID:17660390)
  • CB(1)R and CB(2)R are differentially linked to lipid rafts, specialized microdomains of the plasma membrane–REVIEW (PMID:17678969)
  • insulin may play a key role in the obesity-linked dysregulation of the adipose endocannabinoid system at the gene level (PMID:17923791)
  • CB(2) receptors are induced in beta-amyloid plaque-associated microglia and astroglia, respectively, in Down’s syndrome (PMID:18068305)
  • CB2 is densely present in somatostatin-secreting pancreatic delta cells. (PMID:18092149)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriocnr2ENSDARG00000039970
mus_musculusCnr2ENSMUSG00000062585
rattus_norvegicusCnr2ENSRNOG00000009260

Paralogs (18): LPAR2 (ENSG00000064547), CNR1 (ENSG00000118432), MC3R (ENSG00000124089), S1PR4 (ENSG00000125910), GPR12 (ENSG00000132975), GPR6 (ENSG00000146360), GPR119 (ENSG00000147262), MC4R (ENSG00000166603), S1PR1 (ENSG00000170989), LPAR3 (ENSG00000171517), MC5R (ENSG00000176136), S1PR5 (ENSG00000180739), GPR3 (ENSG00000181773), MC2R (ENSG00000185231), LPAR1 (ENSG00000198121), S1PR3 (ENSG00000213694), MC1R (ENSG00000258839), S1PR2 (ENSG00000267534)

Protein

Protein identifiers

Cannabinoid receptor 2 — P34972 (reviewed: P34972)

Alternative names: CX5

All UniProt accessions (1): P34972

UniProt curated annotations — full annotation on UniProt →

Function. Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.

Subcellular location. Cell membrane. Cell projection. Dendrite. Perikaryon.

Tissue specificity. Preferentially expressed in cells of the immune system with higher expression in B-cells and NK cells (at protein level). Expressed in skin in suprabasal layers and hair follicles (at protein level). Highly expressed in tonsil and to a lower extent in spleen, peripheral blood mononuclear cells, and thymus. PubMed:14657172 could not detect expression in normal brain. Expressed in brain by perivascular microglial cells and dorsal root ganglion sensory neurons (at protein level). Two isoforms are produced by alternative promoter usage and differ only in the 5’ UTR: isoform CB2A is observed predominantly in testis with some expression in brain, while isoform CB2B is predominant in spleen and leukocytes.

Post-translational modifications. Constitutively phosphorylated on Ser-352; phosphorylation increases cell internalization and desensitizes the receptor.

Induction. In macrophages, down-regulated by endocannabinoid anandamide/AEA.

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

RefSeq proteins (1): NP_001832* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000276GPCR_RhodpsnFamily
IPR001551Canbinoid_rcpt_2Family
IPR002230Cnbnoid_rcptFamily
IPR017452GPCR_Rhodpsn_7TMDomain

Pfam: PF00001

UniProt features (54 total): helix 15, topological domain 8, mutagenesis site 8, transmembrane region 7, modified residue 4, sequence variant 2, sequence conflict 2, turn 2, strand 2, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

10 structures.

PDBMethodResolution (Å)
5ZTYX-RAY DIFFRACTION2.8
8GURELECTRON MICROSCOPY2.84
6KPFELECTRON MICROSCOPY2.9
8GUSELECTRON MICROSCOPY2.97
8GUTELECTRON MICROSCOPY2.98
8GUQELECTRON MICROSCOPY3.08
8X3LELECTRON MICROSCOPY3.13
6KPCX-RAY DIFFRACTION3.2
6PT0ELECTRON MICROSCOPY3.2
2KI9SOLUTION NMR

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P34972-F184.570.63

Antibody-complex structures (SAbDab): 7 — 6KPF, 6PT0, 8GUQ, 8GUR, 8GUS, 8GUT, 8X3L

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 (4): 335, 336, 338, 352

Glycosylation sites (1): 11

Mutagenesis-validated functional residues (8):

PositionPhenotype
109no effect on agonist binding. affects cannabinoid agonist binding; when associated with g-112.
109no effect on agonist binding.
112affects cannabinoid agonist binding; when associated with a-109.
130loss of ligand binding. alters agonist-induced inhibitory effect on adenylate cyclase.
131no effect on ligand binding. alters agonist-induced inhibitory effect on adenylate cyclase.
201abolishes ligand binding and agonist-induced inhibitory effect on adenylate cyclase.
207abolishes agonist-induced inhibitory effect on adenylate cyclase. no effect on ligand binding.
244loss of ligand binding. alters agonist-induced inhibitory effect on adenylate cyclase.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 251 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_AMINE, GOBP_INFLAMMATORY_RESPONSE, MODULE_64, MORI_IMMATURE_B_LYMPHOCYTE_UP, GOBP_CELL_CELL_SIGNALING, GOBP_LEUKOCYTE_CHEMOTAXIS, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION, GOBP_MAST_CELL_ACTIVATION

GO Biological Process (14): response to amphetamine (GO:0001975), inflammatory response (GO:0006954), immune response (GO:0006955), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), leukocyte chemotaxis (GO:0030595), negative regulation of synaptic transmission, GABAergic (GO:0032229), response to lipopolysaccharide (GO:0032496), negative regulation of mast cell activation (GO:0033004), negative regulation of action potential (GO:0045759), trans-synaptic signaling by endocannabinoid, modulating synaptic transmission (GO:0099553), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), cannabinoid signaling pathway (GO:0038171)

GO Molecular Function (3): cannabinoid receptor activity (GO:0004949), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (10): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), dendrite (GO:0030425), extrinsic component of cytoplasmic side of plasma membrane (GO:0031234), perikaryon (GO:0043204), postsynaptic membrane (GO:0045211), membrane (GO:0016020), cell projection (GO:0042995), neuronal cell body (GO:0043025)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
GPCR ligand binding1
GPCR downstream signalling1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure4
G protein-coupled receptor signaling pathway3
G protein-coupled receptor activity2
response to amine1
defense response1
immune system process1
response to stimulus1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway1
adenylate cyclase activator activity1
leukocyte migration1
cell chemotaxis1
regulation of synaptic transmission, GABAergic1
negative regulation of synaptic transmission1
synaptic transmission, GABAergic1
response to molecule of bacterial origin1
response to lipid1
response to oxygen-containing compound1
negative regulation of leukocyte activation1
regulation of mast cell activation1
mast cell activation1
action potential1
negative regulation of biological process1
regulation of action potential1
trans-synaptic signaling by endocannabinoid1
trans-synaptic signaling by lipid, modulating synaptic transmission1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
signal transduction1
cannabinoid receptor activity1
cannabinoid signaling pathway1
transmembrane signaling receptor activity1
binding1
intracellular anatomical structure1
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1
membrane1

Protein interactions and networks

STRING

1032 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CNR2ZC3H12DA2A288899
CNR2FAAHO00519887
CNR2GJE1A6NN92806
CNR2IL17CQ9P0M4701
CNR2RC3H1Q5TC82687
CNR2GPR55Q9Y2T6667
CNR2NAPEPLDQ6IQ20618
CNR2MGLLQ99685605
CNR2TRPV1Q8NER1591
CNR2CNR1P21554585
CNR2GJC1P36383526
CNR2DAGLAQ9Y4D2522
CNR2SERPINA6P08185502
CNR2DAGLBQ8NCG7484
CNR2GPR18Q14330481

IntAct

94 interactions, top by confidence:

ABTypeScore
COMTCNR2psi-mi:“MI:0915”(physical association)0.560
SLC39A2CNR2psi-mi:“MI:0915”(physical association)0.560
FXYD3CNR2psi-mi:“MI:0915”(physical association)0.560
CNR2SLC39A2psi-mi:“MI:0915”(physical association)0.560
CNR2NRMpsi-mi:“MI:0915”(physical association)0.560
CNR2TMEM242psi-mi:“MI:0915”(physical association)0.560
CNR2TMEM203psi-mi:“MI:0915”(physical association)0.560
PEDS1-UBE2V1CNR2psi-mi:“MI:0915”(physical association)0.560
CNR2YIPF1psi-mi:“MI:0915”(physical association)0.560
CNR2ADIPOQpsi-mi:“MI:0915”(physical association)0.560
CNR2RFT1psi-mi:“MI:0915”(physical association)0.560
CNR2YIPF4psi-mi:“MI:0915”(physical association)0.560
CNR2MUC15psi-mi:“MI:0915”(physical association)0.560
CNR2TMEM86Apsi-mi:“MI:0915”(physical association)0.560
CNR2SELENOKpsi-mi:“MI:0915”(physical association)0.560
CNR2YIPF6psi-mi:“MI:0915”(physical association)0.560
CCL4CNR2psi-mi:“MI:0915”(physical association)0.560
CNR2SLC35E4psi-mi:“MI:0915”(physical association)0.560
CNR2TMPPEpsi-mi:“MI:0915”(physical association)0.560
CNR2TMEM19psi-mi:“MI:0915”(physical association)0.560
CNR2FXYD3psi-mi:“MI:0915”(physical association)0.560
CNR2TSPO2psi-mi:“MI:0915”(physical association)0.560
CNR2AGPAT4psi-mi:“MI:0915”(physical association)0.560
CNR2TMEM60psi-mi:“MI:0915”(physical association)0.560
CNR2ADAM21psi-mi:“MI:0915”(physical association)0.560
SQSTM1CNR2psi-mi:“MI:0915”(physical association)0.560

BioGRID (109): CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid), CNR2 (Two-hybrid)

ESM2 similar proteins: A5D7K8, O35932, O95136, O95977, P21731, P30557, P30987, P34972, P34978, P34979, P34980, P35375, P35408, P37289, P43088, P43114, P43115, P43116, P43117, P43118, P43119, P43252, P43253, P46069, P47752, P47901, P47936, P50131, P52592, P56486, P70263, P70597, P79393, Q13258, Q28691, Q28905, Q5R949, Q62053, Q62928, Q8MJ08

Diamond homologs: O02777, O08530, O77408, O77621, O95136, P20272, P21453, P21554, P30546, P30966, P31389, P31390, P34972, P35367, P47746, P47752, P47936, P48303, P52592, P56971, P70174, Q17232, Q28928, Q333S9, Q5E9P3, Q5IS73, Q71SP5, Q7JQF1, Q801M1, Q90WY5, Q98894, Q98895, Q9DDK4, Q9H228, Q9I8K8, Q9N2B0, Q9N2B1, Q9N2B2, Q9PUI7, Q9PUQ8

SIGNOR signaling

7 interactions.

AEffectBMechanism
CNR2“up-regulates activity”GNAI1binding
CNR2“up-regulates activity”GNAI3binding
CNR2“up-regulates activity”GNAO1binding
CNR2“up-regulates activity”GNAZbinding
5-(1,1-Dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol“up-regulates activity”CNR2“chemical activation”
Delta(9)-tetrahydrocannabinol“up-regulates activity”CNR2“chemical activation”
MLKL“down-regulates quantity by destabilization”CNR2phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance52
Likely benign1
Benign2

Top pathogenic / likely-pathogenic (0)

SpliceAI

708 predictions. Top by Δscore:

VariantEffectΔscore
1:23913244:A:ACdonor_gain1.0000
1:23913245:C:CCdonor_gain1.0000
1:23913245:CGGTT:Cdonor_gain1.0000
1:23875658:CTTTG:Cacceptor_gain0.9900
1:23875668:G:GCacceptor_gain0.9900
1:23913238:CTACT:Cdonor_loss0.9900
1:23913242:TCA:Tdonor_loss0.9900
1:23913243:CAC:Cdonor_loss0.9900
1:23913244:AC:Adonor_loss0.9900
1:23913245:CG:Cdonor_gain0.9900
1:23913245:CGG:Cdonor_gain0.9900
1:23913245:CGGT:Cdonor_gain0.9900
1:23875659:TTTG:Tacceptor_gain0.9800
1:23875660:TTG:Tacceptor_gain0.9800
1:23875666:CAG:Cacceptor_gain0.9800
1:23875668:G:Cacceptor_gain0.9800
1:23878851:C:CTacceptor_gain0.9800
1:23875661:TG:Tacceptor_gain0.9700
1:23875662:GC:Gacceptor_loss0.9700
1:23875663:C:CAacceptor_loss0.9700
1:23875663:C:CCacceptor_gain0.9700
1:23883278:CA:Cdonor_gain0.9700
1:23913240:A:ACdonor_gain0.9700
1:23913241:C:CCdonor_gain0.9700
1:23875667:A:Tacceptor_gain0.9600
1:23878852:A:Tacceptor_gain0.9600
1:23913240:ACT:Adonor_loss0.9600
1:23875671:C:CTacceptor_gain0.9500
1:23875672:A:Tacceptor_gain0.9500
1:23901557:C:CTdonor_gain0.9500

AlphaMissense

2328 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
1:23875249:G:CS123R0.996
1:23875249:G:TS123R0.996
1:23875251:T:GS123R0.996
1:23875393:G:CS75R0.996
1:23875393:G:TS75R0.996
1:23875395:T:GS75R0.996
1:23875366:A:CS84R0.995
1:23875366:A:TS84R0.995
1:23875368:T:GS84R0.995
1:23875146:A:GW158R0.987
1:23875146:A:TW158R0.987
1:23875282:G:CS112R0.987
1:23875282:G:TS112R0.987
1:23875284:T:GS112R0.987
1:23875378:G:CD80E0.982
1:23875378:G:TD80E0.982
1:23875477:A:CS47R0.982
1:23875477:A:TS47R0.982
1:23875479:T:GS47R0.982
1:23874756:A:GC288R0.979
1:23874846:A:GW258R0.979
1:23874846:A:TW258R0.979
1:23875500:A:GC40R0.979
1:23875357:A:CF87L0.978
1:23875357:A:TF87L0.978
1:23875359:A:GF87L0.978
1:23874775:A:CF281L0.975
1:23874775:A:TF281L0.975
1:23874777:A:GF281L0.975
1:23874733:G:CN295K0.973

dbSNP variants (sampled 300 via entrez): RS1000029053 (1:23889975 C>T), RS1000317078 (1:23876076 C>T), RS1000379759 (1:23881403 C>A), RS1000410652 (1:23881198 C>G,T), RS1000489968 (1:23874539 C>A), RS1000506524 (1:23903818 T>A), RS1000549245 (1:23886017 G>A), RS1000596327 (1:23911031 C>G), RS1000782393 (1:23909933 A>C), RS1000898545 (1:23905958 G>T), RS1000915319 (1:23870137 C>T), RS1000919043 (1:23877363 C>A,T), RS1000943191 (1:23903531 C>T), RS1001003602 (1:23910776 G>C), RS1001009321 (1:23899475 G>A)

Disease associations

OMIM: gene MIM:605051 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

StudyTraitp-value
GCST004600_58Eosinophil percentage of white cells3.000000e-11
GCST004606_180Eosinophil count2.000000e-11
GCST004617_52Eosinophil percentage of granulocytes1.000000e-09
GCST008896_1Psychotic experience (distressing)4.000000e-08
GCST009597_260Multiple sclerosis4.000000e-08
GCST90002381_567Eosinophil count5.000000e-20
GCST90002382_63Eosinophil percentage of white cells4.000000e-21
GCST90002388_600Lymphocyte count1.000000e-13
GCST90002389_80Lymphocyte percentage of white cells7.000000e-09
GCST90002392_154Mean corpuscular volume3.000000e-09

EFO canonical traits (6, from GWAS)

EFO IDTrait name
EFO:0007991eosinophil percentage of leukocytes
EFO:0004842eosinophil count
EFO:0007996eosinophil percentage of granulocytes
EFO:0005940psychotic symptoms
EFO:0004587lymphocyte count
EFO:0007993lymphocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096981 (PROTEIN FAMILY), CHEMBL253 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

27 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 159,980 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL465DRONABINOL462,107
CHEMBL111RIMONABANT415,726
CHEMBL190461CANNABIDIOL426,379
CHEMBL2218896NABILONE4181
CHEMBL220360TARANABANT3612
CHEMBL297453EPIGALOCATECHIN GALLATE322,804
CHEMBL334533DEXANABINOL31,014
CHEMBL456341LENABASUM31,313
CHEMBL562668OTENABANT3243
CHEMBL74415CANNABINOL318,794
CHEMBL267227DELTA-8-TETRAHYDROCANNABINOL2301
CHEMBL1651534REDAFAMDASTAT2102
CHEMBL1684950SUVECALTAMIDE270
CHEMBL189676SURINABANT2332
CHEMBL2019090S-777469214
CHEMBL225411GW842166X299
CHEMBL2387541TETRAHYDROCANNABIVARIN24,884
CHEMBL2387742CANNABIDIVARIN24,963
CHEMBL3139186LY2828360211
CHEMBL3234035PRS-211375231
CHEMBL3234681TEDALINAB2
CHEMBL412262IBIPINABANT2
CHEMBL4175981OLORINAB2
CHEMBL497318CANNABIGEROL2
CHEMBL2397751SAD4481
CHEMBL3613118ONTERNABEZ1
CHEMBL445740BETA-CARYOPHYLLENE1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Cannabinoid receptors

Most potent curated ligand interactions (43 total), top 25:

LigandActionAffinityParameter
[3H]HU-243Full agonist10.2pKd
AM10257Antagonist10.12pKi
MDMB-FubinacaAgonist9.89pKi
HU-210Full agonist9.8pKi
[3H]CP55940Full agonist9.7pKd
WIN55212-2Full agonist9.6pKi
CP55940Full agonist9.2pKi
SR144528Antagonist9.2pKi
AZD1940Agonist9.06pKi
vicasinabinAgonist8.85pEC50
Sch.336Inverse agonist8.74pKi
[3H]WIN55212-2Full agonist8.7pKd
AM7499Agonist8.51pKi
JWH-133Full agonist8.5pKi
JWH-018Full agonist8.5pKi
olorinabFull agonist8.21pEC50
L-759,633Full agonist8.2pKi
nabiloneAgonist8.2pKi
AM1710Agonist8.17pKi
AM1241Agonist8.1pKi
L-759,656Full agonist7.9pKi
cannabinorAgonist7.76pEC50
CB-13Agonist7.72pKi
onternabezFull agonist7.6pKi
Δ9-tetrahydrocannabinolPartial agonist7.5pKi

Binding affinities (BindingDB)

1614 measured of 3128 human assays (3144 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
dibenzothiazepine, 12eKI0.2 nM
dibenzothiazepine, 12hKI0.2 nM
4-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-1-phenylcyclohexane-1-carboxamideKI0.28 nMUS-9187480: Peripherally restricted diphenyl purine derivatives
N-[5-tert-butyl-3-[[(2R)-oxolan-2-yl]methyl]-1,3-thiazol-2-ylidene]-2-(propan-2-ylamino)oxy-5-(trifluoromethyl)benzamideKI0.3 nMUS-8846730: Compounds as cannabinoid receptor ligands
tert-butyl N-[2-[(3-butyl-5-tert-butyl-1,3,4-thiadiazol-2-ylidene)carbamoyl]-4-(trifluoromethyl)phenoxy]carbamateKI0.32 nMUS-8859596: Compounds as cannabinoid receptor ligands
dibenzothiazepine, 12bKI0.32 nM
JWH-051KI0.33 nM
tert-butyl N-[2-[[5-tert-butyl-3-[[(2R)-oxolan-2-yl]methyl]-1,3-thiazol-2-ylidene]carbamoyl]-4-(trifluoromethyl)anilino]carbamateKI0.4 nMUS-8846730: Compounds as cannabinoid receptor ligands
N-(3-butyl-5-tert-butyl-1,3,4-thiadiazol-2-ylidene)-2-[2-(2,2-dimethylpropanoyl)hydrazinyl]-5-(trifluoromethyl)benzamideKI0.4 nMUS-8859596: Compounds as cannabinoid receptor ligands
N-(2-butyl-5-tert-butyl-1-methylpyrazol-3-ylidene)-2-[2-(2,2-dimethylpropanoyl)hydrazinyl]-5-(trifluoromethyl)benzamideKI0.4 nMUS-8859596: Compounds as cannabinoid receptor ligands
2-[2-chloro-5-[4-[2-(4-fluorophenyl)ethylamino]-6-methoxy-1,3,5-triazin-2-yl]phenyl]propan-2-olIC500.4 nMUS-9115121: 1,3,5-triazine-2-amine derivatives, preparation thereof and diagnostic and therapeutic use thereof
methyl (2S)-2-[[6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)pyrazine-2-carbonyl]amino]-4-methylpentanoateEC500.4 nMUS-9403808: Pyrazine derivatives
(R)-3-(1,1-Dimethyl-heptyl)-9-hydroxymethyl-6,6-dimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-olKI0.41 nM
N-[5-tert-butyl-3-[[(2R)-oxolan-2-yl]methyl]-1,3-thiazol-2-ylidene]-2-[[(2S)-oxolan-2-yl]methoxy]-5-(trifluoromethyl)benzamideKI0.5 nMUS-8846730: Compounds as cannabinoid receptor ligands
N-[5-tert-butyl-3-(oxolan-2-ylmethyl)-1,3-thiazol-2-ylidene]-2-(cyclopentylideneamino)oxy-5-(trifluoromethyl)benzamideKI0.5 nMUS-8846730: Compounds as cannabinoid receptor ligands
6-[(4-chlorophenyl)-(4-methoxyphenyl)methyl]-N-(1-phenylpiperidin-4-yl)quinazolin-4-amineEC500.5 nMUS-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
N-(3-butyl-5-tert-butyl-1,3,4-thiadiazol-2-ylidene)-2-(propan-2-ylamino)oxy-5-(trifluoromethyl)benzamideKI0.6 nMUS-8859596: Compounds as cannabinoid receptor ligands
N-(3-butyl-5-tert-butyl-1,3,4-thiadiazol-2-ylidene)-2-(2,2-dimethylpropanoylamino)oxy-5-(trifluoromethyl)benzamideKI0.6 nMUS-8859596: Compounds as cannabinoid receptor ligands
pyrazolopyrimidinone-based antagonist, 3KI0.6 nM
CHEMBL5273987KI0.63 nM
methyl N-[2-[(3-butyl-5-tert-butyl-1,3,4-thiadiazol-2-ylidene)carbamoyl]-4-(trifluoromethyl)anilino]carbamateKI0.7 nMUS-8859596: Compounds as cannabinoid receptor ligands
N-(2-butyl-5-tert-butyl-1-methylpyrazol-3-ylidene)-2-[2-(pyridine-4-carbonyl)hydrazinyl]-5-(trifluoromethyl)benzamideKI0.7 nMUS-8859596: Compounds as cannabinoid receptor ligands
lactam-based compound, 12iKI0.7 nM
ether-based lactam, 19eEC500.7 nM
CHEMBL3409318KI0.7 nM
N-(Adamantan-1-yl)-6-(furan-2-yl)-4-oxo-1-pentyl-1,4-dihydroquinoline-3-carboxamideKI0.7 nM
N-[5-tert-butyl-3-[[(2R)-oxolan-2-yl]methyl]-1,3-thiazol-2-ylidene]-2-[[(2S)-piperidin-2-yl]methoxy]-5-(trifluoromethyl)benzamideKI0.7 nMUS-8846730: Compounds as cannabinoid receptor ligands
N-[5-tert-butyl-3-[[(2R)-oxolan-2-yl]methyl]-1,3-thiazol-2-ylidene]-2-[[(2S)-1-methylpiperidin-2-yl]methoxy]-5-(trifluoromethyl)benzamideKI0.7 nMUS-8846730: Compounds as cannabinoid receptor ligands
N-[5-tert-butyl-3-(2-methylpropyl)-1,3-thiazol-2-ylidene]-2-(2-hydroxyethoxy)-5-(trifluoromethyl)benzamideKI0.73 nMUS-8895592: Compounds as cannabinoid receptor ligands
dibenzothiazepine, 12cKI0.79 nM
N-(3-butyl-5-tert-butyl-1,3,4-thiadiazol-2-ylidene)-2-[2-(pyridine-4-carbonyl)hydrazinyl]-5-(trifluoromethyl)benzamideKI0.8 nMUS-8859596: Compounds as cannabinoid receptor ligands
N-(3-butyl-5-tert-butyl-1,3-thiazol-2-ylidene)-2-(2-hydroxy-2-methylpropoxy)-5-(trifluoromethyl)benzamideKI0.82 nMUS-8895592: Compounds as cannabinoid receptor ligands
PF-514273EC500.82 nM
CHEMBL2381809KI0.84 nM
N-[5-tert-butyl-3-[[(2R)-oxolan-2-yl]methyl]-1,3-thiazol-2-ylidene]-2-(3,3-dimethyl-2-oxobutoxy)-5-(trifluoromethyl)benzamideKI0.9 nMUS-8846730: Compounds as cannabinoid receptor ligands
5-[bis(4-chlorophenyl)methyl]-2-cyclopropyl-3-[1-(2-methoxyphenyl)sulfonylpiperidin-4-yl]indazoleEC501 nMUS-9682940: Indazole derivatives useful as CB-1 inverse agonists
2-acetamidooxy-N-(3-butyl-5-tert-butyl-1,3,4-thiadiazol-2-ylidene)-5-(trifluoromethyl)benzamideKI1 nMUS-8859596: Compounds as cannabinoid receptor ligands
tert-butyl N-[2-[(3-butyl-5-tert-butyl-1,3,4-thiadiazol-2-ylidene)carbamoyl]-4-(trifluoromethyl)anilino]carbamateKI1 nMUS-8859596: Compounds as cannabinoid receptor ligands
4-[[6-[bis(4-chlorophenyl)methyl]quinazolin-4-yl]amino]-1-phenylcyclohexan-1-olEC501 nMUS-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
6-[bis(4-fluorophenyl)methyl]-N-(1-phenylpiperidin-4-yl)quinazolin-4-amineEC501 nMUS-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
2-[5-[4-[2-(4-fluorophenyl)ethylamino]-6-methoxy-1,3,5-triazin-2-yl]-2-methoxyphenyl]propan-2-olIC501 nMUS-9115121: 1,3,5-triazine-2-amine derivatives, preparation thereof and diagnostic and therapeutic use thereof
N-[2-(4-fluorophenyl)ethyl]-4-(5-fluoroquinolin-8-yl)-6-methoxy-1,3,5-triazin-2-amineIC501 nMUS-9115121: 1,3,5-triazine-2-amine derivatives, preparation thereof and diagnostic and therapeutic use thereof
2-[2-chloro-5-[4-[2-(4-fluorophenyl)ethylamino]-6-methoxy-1,3,5-triazin-2-yl]phenoxy]acetamideIC501 nMUS-9115121: 1,3,5-triazine-2-amine derivatives, preparation thereof and diagnostic and therapeutic use thereof
5-Ethyl-2-methyl-1-phenyl-1H-imidazole-4-carboxylic acid adamantan-1-ylamideKI1.03 nM
N-[5-tert-butyl-3-[[(2R)-oxolan-2-yl]methyl]-1,3-thiazol-2-ylidene]-2-[(2R)-2-hydroxypropoxy]-5-(trifluoromethyl)benzamideKI1.1 nMUS-8846730: Compounds as cannabinoid receptor ligands
N-(3-butyl-5-tert-butyl-1,3,4-thiadiazol-2-ylidene)-2-[2-(pyridine-3-carbonyl)hydrazinyl]-5-(trifluoromethyl)benzamideKI1.1 nMUS-8859596: Compounds as cannabinoid receptor ligands
N-(3-butyl-5-tert-butyl-1,3-thiazol-2-ylidene)-2-[2-(pyridine-4-carbonyl)hydrazinyl]-5-(trifluoromethyl)benzamideKI1.1 nMUS-8895592: Compounds as cannabinoid receptor ligands
2-acetamidooxy-N-[5-tert-butyl-3-[[(2R)-oxolan-2-yl]methyl]-1,3-thiazol-2-ylidene]-5-(trifluoromethyl)benzamideKI1.2 nMUS-8846730: Compounds as cannabinoid receptor ligands
2-[2-chloro-5-[4-[2-[4-(difluoromethoxy)phenyl]ethylamino]-6-methoxy-1,3,5-triazin-2-yl]phenyl]propan-2-olIC501.2 nMUS-9115121: 1,3,5-triazine-2-amine derivatives, preparation thereof and diagnostic and therapeutic use thereof
6-[bis(4-chlorophenyl)methyl]-4-[[1-(trifluoromethylsulfonyl)piperidin-4-yl]amino]-3,4,4a,5,6,7,8,8a-octahydro-1H-quinolin-2-oneEC501.2 nMUS-9266835: Quinoline derivatives useful as CB-1 inverse agonists

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
11.00Ki0.01nMCHEMBL1822945
10.85Ki0.014nMCHEMBL1822939
10.82EC500.015nMCHEMBL499066
10.72Ki0.019nMCHEMBL600647
10.72Ki0.01901nMCHEMBL600647
10.70Ki0.02nMCHEMBL1822944
10.68Ki0.021nMCHEMBL3410832
10.68Ki0.02099nMCHEMBL3410832
10.68Ki0.021nMCHEMBL1822940
10.64Ki0.023nMCHEMBL371214
10.59Ki0.026nMCHEMBL3410813
10.49Ki0.032nMCHEMBL2112647
10.49Ki0.032nMCHEMBL3233404
10.49Ki0.032nMCHEMBL1277685
10.49Ki0.032nMCHEMBL1822946
10.44Ki0.036nMCHEMBL1822941
10.43Ki0.037nMCHEMBL216276
10.40EC500.04nMCHEMBL3234701
10.40EC500.04nMCHEMBL3400946
10.40Ki0.04nMCHEMBL216276
10.37Ki0.043nMCHEMBL1822942
10.28Ki0.053nMCHEMBL3410818
10.28Ki0.05297nMCHEMBL3410818
10.22EC500.06nMCHEMBL4450922
10.17EC500.067nMCHEMBL3234706
10.15EC500.07nMCHEMBL3234706
10.12Ki0.075nMCHEMBL5266788
10.11EC500.078nMCHEMBL432107
10.10EC500.08nMCHEMBL3400943
10.10EC500.08nMCHEMBL4177060
10.10Ki0.08nMCHEMBL5266788
10.07Ki0.085nMCHEMBL1822943
10.07Ki0.08492nMCHEMBL1822943
10.07Ki0.08511nMCHEMBL569082
10.06Ki0.087nMCHEMBL3410729
10.06Ki0.088nMCHEMBL3410826
10.06Ki0.0869nMCHEMBL3410729
10.06Ki0.0879nMCHEMBL3410826
10.06Ki0.087nMCHEMBL178372
10.05Ki0.09nMCHEMBL2152813
10.05EC500.09nMCHEMBL3235059
10.05Ki0.09nMCHEMBL3410817
10.05Ki0.08995nMCHEMBL3410817
10.05EC500.089nMCHEMBL501472
10.05Ki0.09nMCHEMBL569082
10.03EC500.093nMCHEMBL3235059
10.00Ki0.1nMCHEMBL2152812
10.00Ki0.1nMCHEMBL2387185
10.00EC500.1nMCHEMBL3914627
10.00EC500.1nMCHEMBL5908929

PubChem BioAssay actives

2589 with measured affinity, of 6100 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.

CompoundAssayTypeValueUnit
1-(2,4-dichlorophenyl)-6-methyl-N-piperidin-1-yl-4H-indeno[2,1-d]pyrazole-3-carboxamide1127517: Binding affinity to CB2 receptor (unknown origin)ki<0.0001uM
6-bromo-1-[(4-fluorophenyl)methyl]-N-(4-methylcyclohexyl)-2-oxo-1,8-naphthyridine-3-carboxamide1167199: Displacement of [3H]CP-55,940 from human recombinant CB2R expressed in HEK-293 cells after 90 mins by liquid scintillation countingki0.0001uM
2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol49842: Binding affinity to human CB2 cannabinoid receptor using [3H]CP-55940 in HEK293 EBNA transfected cellski0.0001uM
(6aS,10aS)-9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol289136: Displacement of [3H]CP-55940 from human CB2 receptor expressed in HEK cellski0.0001uM
1-butyl-2-oxo-N-(2-phenylpropan-2-yl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carboxamide749825: Displacement of [3H]-CP-55,940 from human CB2 receptor expressed in CHO cell membraneski0.0001uM
7-methoxy-1-methyl-N-(2-morpholin-4-ylethyl)-2-oxo-8-pentoxyquinoline-3-carboxamide1198061: Binding affinity to CB2 receptor (unknown origin)ki0.0001uM
[1-(oxolan-3-ylmethyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone444909: Displacement of [3H]CP-55940 from human recombinant CB2 receptor expressed in HEK293 cellski0.0001uM
(2,2,3,3-tetramethylcyclopropyl)-[1-(4,4,4-trifluorobutyl)indol-3-yl]methanone444909: Displacement of [3H]CP-55940 from human recombinant CB2 receptor expressed in HEK293 cellski0.0001uM
[6-methyl-1-(oxan-4-ylmethyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone1798067: Radioligand Binding Assay from Article 10.1021/jm7011613: “Indol-3-yl-tetramethylcyclopropyl Ketones: Effects of Indole Ring Substitution on CB2 Cannabinoid Receptor Activity.”ki0.0001uM
[7-methoxy-1-(oxan-4-ylmethyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone1798067: Radioligand Binding Assay from Article 10.1021/jm7011613: “Indol-3-yl-tetramethylcyclopropyl Ketones: Effects of Indole Ring Substitution on CB2 Cannabinoid Receptor Activity.”ki0.0001uM
N-(1,3-benzodioxol-5-ylmethyl)-7-methoxy-2-oxo-8-pentoxychromene-3-carboxamide1198061: Binding affinity to CB2 receptor (unknown origin)ki0.0001uM
N-(1-adamantyl)-1-(5-hydroxypentyl)-4-methyl-5-phenylpyrazole-3-carboxamide1921313: Antagonist activity at human CB2R assessed as beta arrestin-2 recruitment by measuring inhibition constantki0.0001uM
(4Z,7Z)-N-(1-hydroxypropan-2-yl)-9-[3-[(2Z,5Z,8Z)-undeca-2,5,8-trienyl]oxiran-2-yl]nona-4,7-dienamide1350537: Agonist activity at N-terminal FLAG-tagged human CB2 receptor transfected in human HTLA cells assessed as induction of beta-arrestin-recruitment after 8 to 14 hrs by bright-glo luminescence based assayec500.0001uM
(6aR)-9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol49690: Effective concentration for inhibition of human Cannabinoid receptor 2-mediated adenylyl cyclase using African green monkey (COS-7) cells transfected with the cDNA of human CB2 receptorec500.0001uM
(6aR,10aR)-3-(2-cycloheptylpropan-2-yl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol311038: Binding affinity to CB2 receptorki0.0002uM
(6aR,10aR)-3-(2-hexyl-1,3-dioxolan-2-yl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol311038: Binding affinity to CB2 receptorki0.0002uM
9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)benzo[c]chromen-1-ol49690: Effective concentration for inhibition of human Cannabinoid receptor 2-mediated adenylyl cyclase using African green monkey (COS-7) cells transfected with the cDNA of human CB2 receptorec500.0002uM
3-[2-[3-(2,2,3,3-tetramethylcyclopropanecarbonyl)indol-1-yl]ethyl]-1,3-oxazolidin-2-one444909: Displacement of [3H]CP-55940 from human recombinant CB2 receptor expressed in HEK293 cellski0.0002uM
[1-(oxan-4-ylmethyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone1798067: Radioligand Binding Assay from Article 10.1021/jm7011613: “Indol-3-yl-tetramethylcyclopropyl Ketones: Effects of Indole Ring Substitution on CB2 Cannabinoid Receptor Activity.”ki0.0002uM
N-(4-methylcyclohexyl)-1-(2-morpholin-4-ylethyl)-2-oxo-6-thiophen-2-yl-1,8-naphthyridine-3-carboxamide1167199: Displacement of [3H]CP-55,940 from human recombinant CB2R expressed in HEK-293 cells after 90 mins by liquid scintillation countingki0.0002uM
(2R,4R)-9-[(4-fluorophenyl)methyl]-N-(2-phenylpropan-2-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxamide1175744: Agonist activity at human recombinant CB2 receptor expressed in CHOK1 cells assessed as cAMP accumulation by HTRF methodec500.0002uM
2,5-dimethyl-1-phenyl-N-[[2-(trifluoromethyl)phenyl]methyl]imidazole-4-carboxamide458711: Antagonist activity at human CB2 receptor assessed as inhibition of forskolin-stimulated cAMP accumulation after 20 minsec500.0002uM
N-(1-adamantyl)-7-hydroxy-2-methyl-5-oxo-4-pentylpyrazolo[4,3-b]pyridine-6-carboxamide1658163: Displacement of [3H]-CP-55,940 from recombinant human CB2R expressed in HEK293 cell membraneski0.0002uM
N-(1-adamantyl)-5-ethyl-2-methyl-1-phenylimidazole-4-carboxamide458712: Inverse agonist activity at human CB2 receptor assessed as inhibition of forskolin-stimulated cAMP accumulation after 4 hrsec500.0003uM
methyl 2-[[1-(cyclohexylmethyl)-2-oxo-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonyl]amino]-2-methylpropanoate656851: Displacement of [3H]-CP55940 from recombinant human CB2 receptor by scatchard plot analysiski0.0003uM
1-[(4-fluorophenyl)methyl]-6-(furan-2-yl)-N-(4-methylcyclohexyl)-2-oxo-1,8-naphthyridine-3-carboxamide1167199: Displacement of [3H]CP-55,940 from human recombinant CB2R expressed in HEK-293 cells after 90 mins by liquid scintillation countingki0.0003uM
6-(furan-2-yl)-N-(4-methylcyclohexyl)-1-(2-morpholin-4-ylethyl)-2-oxo-1,8-naphthyridine-3-carboxamide1167199: Displacement of [3H]CP-55,940 from human recombinant CB2R expressed in HEK-293 cells after 90 mins by liquid scintillation countingki0.0003uM
butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate1626922: Agonist activity at human CB2 receptor expressed in HEK293 cells assessed as decrease in forskolin-stimulated cAMP levels after 30 minsec500.0003uM
8-[1-[(6aR,9R,10aR)-9-(azidomethyl)-1-hydroxy-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]cyclopentyl]octanenitrile1816556: Displacement of [3H]CP55940 from human CB2 expressed in HEK293 cell membrane assessed as inhibition constant incubated for 1 hr by TopCount scintillation counting methodki0.0003uM
N-[[1-[4-chloro-2-(2-fluorophenyl)sulfonylphenyl]sulfonyl-4-methylpiperidin-4-yl]methyl]-1,1,1-trifluoromethanesulfonamide454624: Binding affinity to human CB2 receptorki0.0004uM
1,1,1-trifluoro-N-[[1-[1-(2-fluorophenyl)sulfonylindol-2-yl]sulfonylpiperidin-4-yl]methyl]methanesulfonamide526516: Inhibition of beta-arrestin binding to recombinant cannabinoid CB2 receptorki0.0004uM
2-(1-adamantylmethyl)-5-pentylpyrazolo[4,3-c]quinolin-3-one1202980: Displacement of [3H]-CP55940 from human CB2 receptor after 1 hr by scintillation counting analysiski0.0004uM
N-[(1S)-1-[4-[4-methoxy-2-(4-methoxyphenyl)sulfonylphenyl]sulfonylphenyl]ethyl]methanesulfonamide254308: Inhibition constant against Cannabinoid receptor 2ki0.0004uM
[(9aS)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl]-[(11R)-11-cyclohexyl-9-oxa-1-azatricyclo[6.3.1.04,12]dodeca-2,4(12),5,7-tetraen-3-yl]methanone537910: Displacement of [3H]-CP55940 from human CB2 expressed in insect Sf9 membraneski0.0004uM
[1-(4-methylsulfanylbutyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone444909: Displacement of [3H]CP-55940 from human recombinant CB2 receptor expressed in HEK293 cellski0.0004uM
1,1,1-trifluoro-N-[(2S)-6-(1-pyridin-2-ylsulfonylindol-2-yl)sulfonyl-6-azaspiro[2.5]octan-2-yl]methanesulfonamide526516: Inhibition of beta-arrestin binding to recombinant cannabinoid CB2 receptorki0.0004uM
(2R,4R)-9-(2,4-difluorophenyl)-N-(2-methyl-1-morpholin-4-ylpropan-2-yl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-diene-7-carboxamide1175744: Agonist activity at human recombinant CB2 receptor expressed in CHOK1 cells assessed as cAMP accumulation by HTRF methodec500.0004uM
4-[(Z)-1-[(6aS,10aS)-1-hydroxy-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-3-yl]ethylideneamino]oxybutanenitrile1399861: Displacement of [3H]CP-55,940 from recombinant human Cb2 receptor expressed in HEK293 cellski0.0004uM
3-[3-(1-adamantyl)-1,2,4-oxadiazol-5-yl]-6-(furan-2-yl)-1-pentylquinolin-4-one1727010: Displacement of [3H]CP-55940 from human CB2 receptor expressed in HEK cells by competitive binding assayki0.0004uM
8-[1-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]cyclopentyl]octanenitrile1816556: Displacement of [3H]CP55940 from human CB2 expressed in HEK293 cell membrane assessed as inhibition constant incubated for 1 hr by TopCount scintillation counting methodki0.0004uM
8-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-8-methylnonanenitrile1816556: Displacement of [3H]CP55940 from human CB2 expressed in HEK293 cell membrane assessed as inhibition constant incubated for 1 hr by TopCount scintillation counting methodki0.0004uM
(6aR,9R,10aR)-9-(hydroxymethyl)-3-[1-(7-isothiocyanatoheptyl)cyclopentyl]-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-1-ol1816562: Agonist activity at 3xHA tagged human CB2 receptor expressed in CHO-K1 cells assessed as reduction in forskolin-stimulated cAMP accumulation incubated for 30 mins by cAMP assayec500.0004uM
(6aR,10aR)-3-(2-hexyl-1,3-dithiolan-2-yl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol311038: Binding affinity to CB2 receptorki0.0005uM
(6aR,10aR)-9-(hydroxymethyl)-6,6-dimethyl-3-nonyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol49832: Ability to bind with Cannabinoid receptor 2 using [H]CP-55940 as radioligand from cloned human receptor preparationki0.0005uM
(7-methylnaphthalen-1-yl)-(2-methyl-1-pentylindol-3-yl)methanone419195: Displacement of [3H]CP-55940 from human cloned CB2 receptor by filtration assayki0.0005uM
[6-methoxy-1-(oxan-4-ylmethyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone1798067: Radioligand Binding Assay from Article 10.1021/jm7011613: “Indol-3-yl-tetramethylcyclopropyl Ketones: Effects of Indole Ring Substitution on CB2 Cannabinoid Receptor Activity.”ki0.0005uM
[1-[(1-methylpiperidin-2-yl)methyl]indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone444909: Displacement of [3H]CP-55940 from human recombinant CB2 receptor expressed in HEK293 cellski0.0005uM
[1-(2-morpholin-4-ylethyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone444916: Agonist activity at human recombinant CB2 receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP productionec500.0005uM
N-[2-(4-hydroxyphenyl)ethyl]-7-methoxy-2-oxo-8-pentoxy-1H-quinoline-3-carboxamide1198061: Binding affinity to CB2 receptor (unknown origin)ki0.0005uM
N-[(1S)-1-[4-[2-(2-fluorophenyl)sulfonyl-4-methylphenyl]sulfonylphenyl]ethyl]methanesulfonamide254308: Inhibition constant against Cannabinoid receptor 2ki0.0005uM

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanolaffects response to substance, increases phosphorylation, affects binding, decreases reaction, increases activity (+8 more)33
Dronabinolincreases response to substance, affects binding, affects cotreatment, affects localization, increases reaction (+5 more)17
(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanoneaffects cotreatment, decreases reaction, increases expression, affects reaction, increases activity (+4 more)12
SR 144528affects cotreatment, affects binding, decreases reaction, increases transport, increases reaction (+5 more)10
1-pentyl-3-(1-naphthoyl)indoleincreases reaction, affects binding, decreases reaction, increases activity, increases chemical synthesis7
Colforsindecreases reaction, increases activity, increases chemical synthesis, increases abundance, affects response to substance (+3 more)6
Guanosine 5’-O-(3-Thiotriphosphate)decreases reaction, affects binding, increases reaction6
anandamideaffects activity, affects binding, increases activity, affects reaction, affects response to substance5
glyceryl 2-arachidonateaffects response to substance, increases transport, affects binding, increases activity, affects localization (+5 more)5
Pertussis Toxinaffects reaction, affects response to substance, decreases reaction, increases abundance, increases phosphorylation (+3 more)5
methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoateincreases reaction, increases activity, affects binding, decreases reaction4
Cannabidioldecreases reaction, decreases secretion, increases reaction, affects expression, affects binding (+1 more)4
1-pentyl-1H-indole-3-carboxylic acid 8-quinolinyl esteraffects binding, decreases reaction, increases activity, increases chemical synthesis, increases reaction3
1-(5-fluoropentyl)-3-(4-methyl-1-naphthoyl)indoleaffects binding, decreases reaction, increases activity, increases chemical synthesis, increases reaction3
N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamideaffects binding, increases activity, decreases reaction, increases chemical synthesis3
(4-ethyl-1-naphthalenyl)(1-(5-fluoropentyl)-1H-indol-3-yl)methanoneincreases activity, increases chemical synthesis, increases reaction, affects binding, decreases reaction3
AB-FUBINACAdecreases reaction, affects binding, increases activity3
caryophylleneaffects cotreatment, increases expression, affects reaction, increases phosphorylation, decreases reaction (+1 more)3
iodopravadolineaffects localization, affects binding, decreases activity, decreases reaction, increases activity3
JHW 015affects binding, increases activity, affects localization, increases reaction3
N’-((3Z)-1-(1-hexyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene)benzohydrazideincreases activity, decreases reaction, affects expression, affects reaction, affects phosphorylation (+1 more)3
4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanoneaffects binding, decreases reaction, increases reaction, increases activity3
XLR-11decreases activity, decreases reaction, increases activity, affects binding, increases chemical synthesis (+1 more)3
(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanoneaffects binding, increases activity, decreases reaction, increases chemical synthesis, increases reaction3
N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamideaffects binding, increases activity2
N-(1-(aminocarbonyl)-2-methylpropyl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamideaffects binding, increases activity2
N-(1-adamantyl)-1-pentylindazole-3-carboxamidedecreases reaction, increases activity, increases chemical synthesis, affects binding2
methyl 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoateaffects binding, increases activity, decreases reaction2
methyl (1-(5-fluoropentyl)-1H-indazole-3-carbonyl)valinatedecreases reaction, affects binding, increases activity2
5F-ADB cannabinoidaffects binding, increases activity, decreases reaction2

ChEMBL screening assays

1590 unique, capped per target: 872 binding, 712 functional, 5 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1838787BindingBinding affinity to CB receptor in human cortex membranesConformationally constrained analogs of BAY 59-3074 as novel cannabinoid receptor ligands. — Bioorg Med Chem Lett
CHEMBL5364352FunctionalAgonist activity at CB1/CB2 (unknown origin) receptor expressed in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 2 hrs by microplate reader analysisCannabidiol Analogue CIAC001 for the Treatment of Morphine-Induced Addiction by Targeting PKM2. — J Med Chem
CHEMBL4364975ADMETDisplacement of [3H]CP55940 from human CB2 receptor expressed in HEK293 cell membranesFunctionalized 6-(Piperidin-1-yl)-8,9-Diphenyl Purines as Peripherally Restricted Inverse Agonists of the CB1 Receptor. — J Med Chem

Cellosaurus cell lines

11 cell lines: 4 cancer cell line, 4 transformed cell line, 3 spontaneously immortalized cell line

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

CellosaurusNameCategorySex
CVCL_B7WSAbcam Raji CNR2 KOCancer cell lineMale
CVCL_B9XBAbcam THP-1 CNR2 KOCancer cell lineMale
CVCL_C0SDACTOne CB2Transformed cell lineFemale
CVCL_C6Z8Abcam PC-3 CNR2 KOCancer cell lineMale
CVCL_H410CHO-K1/CB2Spontaneously immortalized cell lineFemale
CVCL_KU96cAMP Hunter CHO-K1 CNR2 GiSpontaneously immortalized cell lineFemale
CVCL_KW73PathHunter CHO-K1 CNR2 beta-arrestinSpontaneously immortalized cell lineFemale
CVCL_KZ40PathHunter HEK 293 CNR2 beta-arrestinTransformed cell lineFemale
CVCL_YK09HEK293 CNR2 HiTSeekerTransformed cell lineFemale
CVCL_ZC54HEK293-hCNR2Transformed cell lineFemale

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
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v2.0.2

Sources 81

This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot