CNR1

Summary

CNR1 (cannabinoid receptor 1, HGNC:2159) is a protein-coding gene on chromosome 6q15, encoding Cannabinoid receptor 1 (P21554). G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC).

This gene encodes one of two cannabinoid receptors. The cannabinoids, principally delta-9-tetrahydrocannabinol and synthetic analogs, are psychoactive ingredients of marijuana. The cannabinoid receptors are members of the guanine-nucleotide-binding protein (G-protein) coupled receptor family, which inhibit adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. The two receptors have been found to be involved in the cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana. Multiple transcript variants encoding two different protein isoforms have been described for this gene.

Source: NCBI Gene 1268 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 53 total
• Druggable target: yes — 110 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016083

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2159
Approved symbol	CNR1
Name	cannabinoid receptor 1
Location	6q15
Locus type	gene with protein product
Status	Approved
Aliases	CB1K5, CB-R, CB1, CANN6, CB1A
Ensembl gene	ENSG00000118432
Ensembl biotype	protein_coding
OMIM	114610
Entrez	1268

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 19 protein_coding

ENST00000362094, ENST00000369499, ENST00000369501, ENST00000428600, ENST00000468898, ENST00000549890, ENST00000551417, ENST00000882404, ENST00000882405, ENST00000882406, ENST00000882407, ENST00000882408, ENST00000882409, ENST00000882410, ENST00000882411, ENST00000918489, ENST00000918490, ENST00000918491, ENST00000951387

RefSeq mRNA: 17 — MANE Select: NM_016083 NM_001160226, NM_001160258, NM_001160259, NM_001365869, NM_001365870, NM_001365872, NM_001365874, NM_001370545, NM_001370546, NM_001370547, NM_001424094, NM_001424095, NM_001424096, NM_001424097, NM_001424098, NM_016083, NM_033181

CCDS: CCDS5015, CCDS5016

Canonical transcript exons

ENST00000369501 — 2 exons

Exon	Start	End
ENSE00001450191	88139864	88145337
ENSE00002407758	88165803	88166347

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 99.15.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2220 / max 178.9348, expressed in 517 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74645	2.5160	336
74644	1.1119	380
74646	0.3276	85
74643	0.1310	73
74642	0.0538	20
74641	0.0449	27
74647	0.0367	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.15	gold quality
ventricular zone	UBERON:0003053	95.84	gold quality
decidua	UBERON:0002450	95.48	gold quality
cerebellar vermis	UBERON:0004720	94.09	gold quality
paraflocculus	UBERON:0005351	93.49	gold quality
cortical plate	UBERON:0005343	91.86	gold quality
frontal pole	UBERON:0002795	91.67	gold quality
CA1 field of hippocampus	UBERON:0003881	90.30	gold quality
Brodmann (1909) area 10	UBERON:0013541	90.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.59	gold quality
endothelial cell	CL:0000115	89.08	gold quality
middle frontal gyrus	UBERON:0002702	88.89	gold quality
pericardium	UBERON:0002407	88.76	gold quality
middle temporal gyrus	UBERON:0002771	88.28	gold quality
cerebellum	UBERON:0002037	87.60	gold quality
prefrontal cortex	UBERON:0000451	87.52	gold quality
superior frontal gyrus	UBERON:0002661	87.47	gold quality
orbitofrontal cortex	UBERON:0004167	87.31	gold quality
cerebellar cortex	UBERON:0002129	87.26	gold quality
pituitary gland	UBERON:0000007	87.18	gold quality
cerebellar hemisphere	UBERON:0002245	87.05	gold quality
adenohypophysis	UBERON:0002196	86.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.86	gold quality
omental fat pad	UBERON:0010414	86.69	gold quality
peritoneum	UBERON:0002358	86.56	gold quality
frontal cortex	UBERON:0001870	86.29	gold quality
neocortex	UBERON:0001950	86.28	gold quality
entorhinal cortex	UBERON:0002728	86.05	gold quality
anterior cingulate cortex	UBERON:0009835	85.94	gold quality
cingulate cortex	UBERON:0003027	85.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	946.41
E-ANND-3	yes	5.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, FOXO1, NFKBIB, NR5A1, PAX3, PPARD, RARG, STAT6

miRNA regulators (miRDB)

275 targeting CNR1, 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-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997

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)
• Results are the first report of an significant association between CB1 receptor and a subtype of schizophrenia. (PMID:11803524)
• suggested that homozygous genotype CNR1 1359A/A confers vulnerability to alcohol withdrawal delirium. (PMID:11841893)
• a nigro-striatal lesion is associated with an increase in CB1 receptors in the basal ganglia in humans and nonhuman primates and that this increase could be reversed by chronic l-DOPA therapy. (PMID:11860478)
• recombinant protein shows high potency with an endogenous capsaicin-like substance (PMID:12060783)
• associated with susceptibility to hebephrenic schizophrenia (PMID:12082570)
• role of intracellular loops of cannabinoid CB1 receptor in functional interaction with Galpha16. (PMID:12095632)
• 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)
• CB(1)-induced ERK activation was mediated by PI3K(IB) and this effect may have important consequences in the control of cell death/survival decision. (PMID:12435806)
• both mRNA for CB(1) and the corresponding protein are expressed in human prostate gland at level comparable with the receptor expressed in cerebellum; CB(1) preferentially expressed in prostate epithelia (PMID:12497582)
• CB1 plays a role in inhibiting neovascularization and skin neoplasm development (PMID:12511587)
• evidence that CB1 is able to potentiate an orexigenic receptor, OX1R (PMID:12690115)
• CB1 receptor expression throughout the different areas of the developing human brain suggests a specific role of the endocannabinoid system in the events related to human neural development. (PMID:12752773)
• homology model of the CB(1) cannabinoid receptor (PMID:12767117)
• High level of cannabinoid receptor 1 is associated with mantle cell lymphoma (PMID:12970790)
• CB1 receptor mRNA expression was altered in Parkinson’s disease and was affected by alterations in dopaminergic systems. (PMID:14628192)
• Restricting AN and binging/purging AN may be associated with different alleles of the CNR1 gene coding cannabinoid receptor 1. (PMID:14755457)
• delta(9)-THC induces an influx of extracellular calcium in resting T cells in a CB1- CB2- -dependent manner (PMID:14966196)
• upregulation of CB(1) receptors with concomitant increase in the CB(1) receptor-mediated [(35)S]GTPgammaS binding suggests a role for enhanced cannabinoidergic signaling in the prefrontal cortex of depressed suicides (PMID:14966476)
• A 5’ Cnr1 “TAG” haplotype displays significant allelic frequency differences between substance abusers & controls in European-American, African-American & Japanese samples. Cnr1 genomic variation appears to play roles in human addiction vulnerability. (PMID:15289816)
• the cannabinoid receptor CB1 was not identified in first trimester placenta (PMID:15472222)
• Human sperm express functional CB(1)-R, the activation of which negatively influences important sperm functions such as motility. (PMID:15562018)
• Identification of a splice variant of the human CB1 receptor. (PMID:15620723)
• lipid rafts control CB1R binding and signaling, and CB1R activation underlies the protective effect of methyl-beta-cyclodextrin against apoptosis (PMID:15657045)
• the presence of two long alleles in the cnr1 gene was associated with a reduced prevalence of depression in parkinson disease (PMID:15668727)
• Senile plaques in AD patients express CB1 receptors which show increased nitration. G-protein coupling and CB1 receptor protein expression are markedly decreased in AD brains. (PMID:15728830)
• 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)
• Tole of cysteine residues in CB1 ligand binding and activation, and demonstrate a method for mapping key determinants in CB1 structure and function (PMID:15952782)
• No convincing association is found for cannabinoid receptor type 1 (Cnr1) in a systematic genetic association study in a human sample of postmenopausal osteoporosis patients and matched female controls (PMID:16204352)
• CB1R is associated with cholesterol- and sphyngolipid-enriched membrane domains (rafts). (PMID:16263116)
• CB(1) receptors are stabilized in a conformation that enables G(q)11 signaling by the WIN55212-2 cannabinoid agonist, thus shifting the G protein specificity of the receptor (PMID:16365309)
• 4 SNPs in the CNR1 gene are found to be positively associated with striatal response to happy faces (and not to disgust faces) in humans, using fMRI. (PMID:16623851)
• decreased thermal stability of T210I receptor & increased level of internalization of a T210I receptor-GFP chimera were also observed. Results suggest that T210 plays key role in governing transition between inactive & active CB(1) receptor states. (PMID:16634642)
• Sequential assignments of TM5 and intra-cellular loop 3 were accomplished. The obtained structure also showed alpha-helix in the TM5 region, but it was interrupted by a disordered region (Gly204_ILe206). (PMID:16712507)
• study shows that CB1 receptors are upregulated in the liver of cirrhotic individuals and expressed in liver fibrogenic cells (PMID:16715087)
• Findings fail to replicate the original report of an association between SNPs adjacent to an alternative CNR1 exon 3 transcription start site and polysubstance abuse. (PMID:16741937)
• analysis of human cannabinoid receptor 1 truncation (PMID:16818376)
• A common CNR1 haplotype is associated with developing fewer cannabis dependence symptoms among adolescents who have experimented with cannabis. (PMID:16917946)
• Antagonists may prove beneficial in the treatment of proliferative liver fibrosis. (PMID:16962033)
• lipid rafts control CB1R, but not CB2R, and endocannabinoid transport in immune and neuronal cells. (PMID:17015679)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnr1	ENSDARG00000009020
mus_musculus	Cnr1	ENSMUSG00000044288
rattus_norvegicus	Cnr1	ENSRNOG00000008223

Paralogs (18): LPAR2 (ENSG00000064547), MC3R (ENSG00000124089), S1PR4 (ENSG00000125910), GPR12 (ENSG00000132975), GPR6 (ENSG00000146360), GPR119 (ENSG00000147262), MC4R (ENSG00000166603), S1PR1 (ENSG00000170989), LPAR3 (ENSG00000171517), MC5R (ENSG00000176136), S1PR5 (ENSG00000180739), GPR3 (ENSG00000181773), MC2R (ENSG00000185231), CNR2 (ENSG00000188822), LPAR1 (ENSG00000198121), S1PR3 (ENSG00000213694), MC1R (ENSG00000258839), S1PR2 (ENSG00000267534)

Protein

Protein identifiers

Cannabinoid receptor 1 — P21554 (reviewed: P21554)

Alternative names: CANN6

All UniProt accessions (5): P21554, F8W187, F8W908, S5TLS4, V5KA96

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP. In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission. In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner. In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone. Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes. In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism. In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism. In response to cannabinoid anandamide, elicits a pro-inflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion. In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells. Binds both 2-arachidonoylglycerol (2-AG) and anandamide. Only binds 2-arachidonoylglycerol (2-AG) with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 2 in assays measuring GTP binding to membranes. Only binds 2-arachidonoylglycerol (2-AG) with high affinity. Contrary to its effect on isoform 1, 2-AG behaves as an inverse agonist on isoform 3 in assays measuring GTP binding to membranes.

Subunit / interactions. Interacts (via C-terminus) with CNRIP1; this interaction attenuates constitutive, but not agonist-dependent, inhibition of voltage-gated Ca(2+) channels in neurons. Associates with G protein alpha subunits, including G(i) alpha-1/GNAI1, G(i) alpha-2/GNAI2, G(i) alpha-3/GNAI3 and G(o)-alpha/GNAO1; palmitoylation is important for interaction with GNAI3 and GNAO1.

Subcellular location. Cell membrane. Membrane raft. Mitochondrion outer membrane. Cell projection. Axon. Presynapse.

Tissue specificity. Widely expressed, with highest levels in fetal and adult brain. Expression levels of isoform 2 and isoform 3 are much lower than those of isoform 1.

Post-translational modifications. Palmitoylation at Cys-415 is important for recruitment at plasma membrane and lipid rafts and association with G protein alpha subunits.

Disease relevance. Obesity (OBESITY) [MIM:601665] A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. The protein represented in this entry may be involved in disease pathogenesis. May contribute to the development of diet-induced obesity and several obesity-associated features, such as dyslipidemia and liver steatosis, regulating peripheral lipogenesis, energy expenditure and feeding behavior. CNR1 inverse agonists have been shown to reduce body weight and improve metabolic abnormalities in obese subjects, although adverse neuropsychiatric effects, including anxiety, irritability, and depressed mood, halted their therapeutic development. In obese mice, peripherally restricted CNR1 inverse agonists have been shown to normalize metabolic abnormalities, including insulin resistance and fatty liver, and to reverse leptin resistance. Dysfunction of the endogenous cannabinoid system including CNR1 has been implicated in the pathogenesis of a number of central nervous system disorders, including Huntington disease, Parkinson disease, and Alzheimer disease. In post-mortem brains from Huntington disease patients, a progressive CNR1 loss has been observed in the caudate nucleus, putamen, and substantia nigra pars reticulata, and altered expression and abnormal endocannabinoid levels precede motor symptoms in a disease mouse model. In Parkinson disease, low CNR1 expression in mid-superior frontal gyrus and mid-cingulate cortex has been associated with poor mind, poor executive functioning and poor episode memory, while patients with more severe visuospatial dysfunction showed decreased receptor availability in the precuneus, mid-cingulate, supplementary motor cortex, inferior orbitofrontal gyrus and thalamus. In an animal model for Alzheimer disease, CNR1 heterozygous deletion has been associated with decreased levels of postsynaptic density protein 95 (DLG4/PSD95) and accelerated memory impairment, suggesting synaptic dysfunction and a crucial role for CNR1 in the progression of disease symptoms.

Activity regulation. Hemopressin, a peptide derived from hemoglobin subunit alpha (HBA1 and/or HBA2), acts as an antagonist peptide: hemopressin-binding efficiently blocks cannabinoid receptor CNR1 and subsequent signaling.

Induction. Up-regulated by endocannabinoid anandamide.

Miscellaneous. High-fat diet also increases the hepatic levels of CNR1 ligand anandamide, but not that of 2-arachidonoylglycerol. Dubious isoform. A putative downstream initiation AUG is used to produce isoform 2. The use of the first AUG (same as isoform 1) gives a truncated protein of 36 AA.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P21554-1	1, Long	yes
P21554-2	2, CB1a, Short
P21554-3	3, CB1b

RefSeq proteins (17): NP_001153698, NP_001153730, NP_001153731, NP_001352798, NP_001352799, NP_001352801, NP_001352803, NP_001357474, NP_001357475, NP_001357476, NP_001411023, NP_001411024, NP_001411025, NP_001411026, NP_001411027, NP_057167, NP_149421 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000810	Canbinoid_rcpt_1	Family
IPR002230	Cnbnoid_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (57 total): helix 17, topological domain 8, sequence conflict 8, transmembrane region 7, mutagenesis site 5, modified residue 2, glycosylation site 2, splice variant 2, strand 2, chain 1, region of interest 1, lipid moiety-binding region 1, turn 1

Structure

Experimental structures (PDB)

34 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
23IV	ELECTRON MICROSCOPY	2.42
23IW	ELECTRON MICROSCOPY	2.42
5U09	X-RAY DIFFRACTION	2.6
7FEE	X-RAY DIFFRACTION	2.7
5TGZ	X-RAY DIFFRACTION	2.8
5XRA	X-RAY DIFFRACTION	2.8
8GHV	ELECTRON MICROSCOPY	2.8
9B54	ELECTRON MICROSCOPY	2.86
8K8J	ELECTRON MICROSCOPY	2.88
9ERX	ELECTRON MICROSCOPY	2.9
5XR8	X-RAY DIFFRACTION	2.95
6KPG	ELECTRON MICROSCOPY	3
6N4B	ELECTRON MICROSCOPY	3
9B65	ELECTRON MICROSCOPY	3.03
9BA0	ELECTRON MICROSCOPY	3.13
8WU1	ELECTRON MICROSCOPY	3.2
9EGO	ELECTRON MICROSCOPY	3.2
6KQI	X-RAY DIFFRACTION	3.25
7V3Z	X-RAY DIFFRACTION	3.29
8GAG	ELECTRON MICROSCOPY	3.3
8IKH	ELECTRON MICROSCOPY	3.3
9B9Z	ELECTRON MICROSCOPY	3.3
9DGI	ELECTRON MICROSCOPY	3.35
7WV9	ELECTRON MICROSCOPY	3.36
8IKG	ELECTRON MICROSCOPY	3.4
9B9Y	ELECTRON MICROSCOPY	3.5
8WRZ	ELECTRON MICROSCOPY	3.6
1LVQ	SOLUTION NMR
1LVR	SOLUTION NMR
2B0Y	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21554-F1	72.11	0.48

Antibody-complex structures (SAbDab): 14 — 6KPG, 6N4B, 7WV9, 8GAG, 8GHV, 8IKG, 8IKH, 8K8J, 8WRZ, 8WU1, 9B65, 9B9Y, 9EGO, 9ERX

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 (3): 425, 429, 415

Glycosylation sites (2): 77, 83

Mutagenesis-validated functional residues (5):

Position	Phenotype
155	enhanced g(i) signaling activation ability.
155	reduced agonist-induced receptor activation.
210	7-fold lower affinity for a synthetic agonist, cp55940, possibly due the stabilization of an inactive conformation.
341–342	loss of activity, when assayed for gnai1 gtpase stimulatory activity.
415	loss of palmitoylation, marked loss of association with lipid rafts on the plasma membrane and loss of activity, when as

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: 275 (showing top): chr6q15, TGGTGCT_MIR29A_MIR29B_MIR29C, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, RRAGTTGT_UNKNOWN, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_NEURON_RECOGNITION, MODULE_64, GOBP_NEUROGENESIS, HASLINGER_B_CLL_WITH_11Q23_DELETION, GOBP_CELL_CELL_SIGNALING, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, MODULE_205, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOCC_MITOCHONDRIAL_ENVELOPE

GO Biological Process (10): G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), axonal fasciculation (GO:0007413), cannabinoid signaling pathway (GO:0038171), glucose homeostasis (GO:0042593), retrograde trans-synaptic signaling by endocannabinoid (GO:0098921), regulation of presynaptic cytosolic calcium ion concentration (GO:0099509), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (4): G protein-coupled receptor activity (GO:0004930), cannabinoid receptor activity (GO:0004949), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (15): cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), growth cone (GO:0030426), presynaptic membrane (GO:0042734), membrane raft (GO:0045121), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), mitochondrion (GO:0005739), membrane (GO:0016020), axon (GO:0030424), cell projection (GO:0042995), synapse (GO:0045202), presynapse (GO:0098793)

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
G protein-coupled receptor signaling pathway	4
cellular anatomical structure	4
synapse	3
presynapse	2
G protein-coupled receptor activity	2
adenylate cyclase activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
neuron recognition	1
axon development	1
neuron projection fasciculation	1
cannabinoid receptor activity	1
carbohydrate homeostasis	1
retrograde trans-synaptic signaling by lipid	1
trans-synaptic signaling by endocannabinoid	1
regulation of cytosolic calcium ion concentration	1
neuron cellular homeostasis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
transmembrane signaling receptor activity	1
cannabinoid signaling pathway	1
protein binding	1
binding	1
intracellular anatomical structure	1
mitochondrial membrane	1
organelle outer membrane	1
membrane	1
cell periphery	1
cytoskeleton	1
site of polarized growth	1
distal axon	1
synaptic membrane	1
membrane microdomain	1
cytoplasm	1
intracellular membrane-bounded organelle	1
neuron projection	1

Protein interactions and networks

STRING

1602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNR1	GPR55	Q9Y2T6	974
CNR1	FAAH	O00519	972
CNR1	MGLL	Q99685	941
CNR1	ADORA2A	P29274	884
CNR1	DRD2	P14416	867
CNR1	DAGLA	Q9Y4D2	818
CNR1	NAPEPLD	Q6IQ20	801
CNR1	NTRK2	Q16620	794
CNR1	TRPV1	Q8NER1	778
CNR1	BDNF	P23560	777
CNR1	CNRIP1	Q96F85	745
CNR1	ARRB2	P32121	744
CNR1	ARRB1	P49407	737
CNR1	HCRT	O43612	731
CNR1	GNAQ	P50148	728

IntAct

55 interactions, top by confidence:

A	B	Type	Score
ADORA2A	DRD2	psi-mi:“MI:2364”(proximity)	0.680
ADORA2A	CNR1	psi-mi:“MI:0915”(physical association)	0.680
CNR1	ADORA2A	psi-mi:“MI:2364”(proximity)	0.680
CNR1	ADORA2A	psi-mi:“MI:0403”(colocalization)	0.680
ADRB2	ADRB2	psi-mi:“MI:2364”(proximity)	0.660
CNR1	CNR1	psi-mi:“MI:2364”(proximity)	0.650
CNR1	CNR1	psi-mi:“MI:0915”(physical association)	0.650
CNR2	CNR1	psi-mi:“MI:2364”(proximity)	0.510
CNR2	CNR1	psi-mi:“MI:0403”(colocalization)	0.510
CNR1	DRD2	psi-mi:“MI:2364”(proximity)	0.470
CNR1	DRD2	psi-mi:“MI:0915”(physical association)	0.470
CNR1	HTR2A	psi-mi:“MI:2364”(proximity)	0.450
CNR1	HTR2A	psi-mi:“MI:0915”(physical association)	0.450
	CNR1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	CNR1	psi-mi:“MI:0915”(physical association)	0.400
CNR1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CNR1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (13): SSTR5 (Affinity Capture-Western), SSTR5 (FRET), CNR1 (FRET), NSRP1 (Reconstituted Complex), GNAI1 (Affinity Capture-Western), GNAI2 (Affinity Capture-Western), GNAI3 (Affinity Capture-Western), CNR1 (FRET), CNR1 (FRET), CNR1 (Two-hybrid), GRIN2B (Co-localization), CNR1 (Cross-Linking-MS (XL-MS)), CNR1 (Affinity Capture-Western)

ESM2 similar proteins: A0A2R9YJI3, B2ZHY2, B3DM66, B4XF06, D4A3U0, O02777, O43194, O46635, P08909, P08911, P0C0W8, P14842, P18599, P20272, P21554, P28223, P28335, P32240, P34311, P34968, P35363, P47746, P50128, P50129, P56971, P70259, Q09502, Q333S9, Q5IS53, Q5IS66, Q5IS73, Q5IS98, Q5R4Q6, Q5U431, Q60F97, Q6DWJ6, Q71SP5, Q75Z89, Q801M1, Q80UC8

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

13 interactions.

A	Effect	B	Mechanism
“Org 27569”	down-regulates	CNR1	“chemical inhibition”
CNR1	“up-regulates activity”	GNAO1
CNR1	“up-regulates activity”	GNAI1	binding
CNR1	“up-regulates activity”	GNAI3	binding
CNR1	“up-regulates activity”	GNAO1	binding
CNR1	“up-regulates activity”	GNAZ	binding
CNR1	“up-regulates activity”	GNA14	binding
CNR1	“up-regulates activity”	GNA12	binding
CNR1	“up-regulates activity”	GNA13	binding
5-(1,1-Dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol	“up-regulates activity”	CNR1	“chemical activation”
“episterol ester”	“up-regulates activity”	CNR1	“chemical activation”
Delta(9)-tetrahydrocannabinol	“up-regulates activity”	CNR1	“chemical activation”
CNR1	“up-regulates activity”	HCRTR1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
G alpha (s) signalling events	6	36.6×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-activating G protein-coupled receptor signaling pathway	6	52.2×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

858 predictions. Top by Δscore:

Variant	Effect	Δscore
6:88165801:AC:A	donor_gain	0.9900
6:88165802:CC:C	donor_gain	0.9900
6:88164297:T:C	acceptor_gain	0.9800
6:88166091:T:TA	donor_gain	0.9800
6:88165798:CTTAC:C	donor_loss	0.9600
6:88165799:TTAC:T	donor_loss	0.9600
6:88165800:TACCC:T	donor_loss	0.9600
6:88165801:A:C	donor_loss	0.9600
6:88165802:C:CA	donor_loss	0.9600
6:88164297:T:TC	acceptor_gain	0.9500
6:88165802:CCCTT:C	donor_gain	0.9500
6:88165840:TGGC:T	donor_gain	0.9500
6:88166327:C:CA	donor_gain	0.9500
6:88165801:A:AC	donor_gain	0.9400
6:88165802:C:CC	donor_gain	0.9400
6:88166213:C:A	donor_gain	0.9400
6:88164292:CAT:C	acceptor_gain	0.9300
6:88166212:T:TA	donor_gain	0.9300
6:88164296:T:C	acceptor_gain	0.9200
6:88165664:CAG:C	donor_gain	0.9200
6:88166088:G:A	donor_gain	0.9200
6:88165726:TGGGG:T	donor_gain	0.9100
6:88143912:TG:T	donor_gain	0.8900
6:88164295:C:CC	acceptor_gain	0.8900
6:88143829:T:A	donor_gain	0.8800
6:88145337:CCTAA:C	acceptor_loss	0.8800
6:88145338:C:CA	acceptor_loss	0.8800
6:88145339:T:A	acceptor_loss	0.8800
6:88165836:C:CA	donor_gain	0.8800
6:88145338:C:CC	acceptor_gain	0.8600

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000139586 (6:88166546 G>A), RS1000225400 (6:88154370 T>C), RS1000453745 (6:88158888 T>C), RS1000600398 (6:88150201 C>G), RS1000703054 (6:88165044 ATTTCT>A), RS1000792029 (6:88160199 G>A,C), RS1000937167 (6:88162537 G>C,T), RS1000945401 (6:88153779 A>G), RS1001008397 (6:88147676 G>A,C,T), RS1001009131 (6:88154310 A>C), RS1001056330 (6:88150550 A>C), RS1001087521 (6:88167565 C>T), RS1001275508 (6:88153618 T>A,C), RS1001319748 (6:88166299 T>G), RS1001392591 (6:88162340 A>T)

Disease associations

OMIM: gene MIM:114610 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003854_22	Gut microbiota (functional units)	4.000000e-08
GCST006427_10	Depression in smokers	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2096981 (PROTEIN FAMILY), CHEMBL218 (SINGLE PROTEIN), CHEMBL3301387 (PROTEIN COMPLEX), CHEMBL3885538 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

110 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 579,519 (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
CHEMBL465	DRONABINOL	4	62,107
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1073	GLIPIZIDE	4	42,268
CHEMBL1082407	ENZALUTAMIDE	4	9,652
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL111	RIMONABANT	4	15,726
CHEMBL113	CAFFEINE	4	200,591
CHEMBL116	AMPRENAVIR	4	29,221
CHEMBL1200500	BECLOMETHASONE DIPROPIONATE	4	29,239
CHEMBL1200617	RIMEXOLONE	4	891
CHEMBL1200732	AMCINONIDE	4	16,116
CHEMBL1200989	ALCLOMETASONE DIPROPIONATE	4	8,201
CHEMBL1201151	MESTRANOL	4	10,339
CHEMBL1201271	BUCLIZINE	4	5,799
CHEMBL1201303	PYRVINIUM	4	1,797
CHEMBL1201304	INDOCYANINE GREEN ACID FORM	4	7,044
CHEMBL121	ROSIGLITAZONE	4	58,849
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL1303	ROTIGOTINE	4	832
CHEMBL1428	NIMODIPINE	4
CHEMBL1480	FELODIPINE	4
CHEMBL1525	PERMETHRIN	4
CHEMBL1530428	DEXAMETHASONE ACETATE	4
CHEMBL1623	MECLIZINE	4
CHEMBL1651990	FENTICONAZOLE	4
CHEMBL1670	MITOTANE	4
CHEMBL1676	FLUTICASONE FUROATE	4
CHEMBL1726	NISOLDIPINE	4
CHEMBL175247	ORLISTAT	4

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

PharmGKB clinical annotations

7 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1049353	Toxicity	3	risperidone	Autism Spectrum Disorder;Psychotic Disorder
rs2023239	Toxicity	3	opioids	Opioid-Related Disorders
rs6454674	Other	3	cocaine	Cocaine dependence
rs6928499	Toxicity	3	opioids	Opioid-Related Disorders
rs806368	Other	3	cocaine	Cocaine dependence
rs806368	Dosage	3	methadone	Heroin Dependence
rs806378	Toxicity	3	clozapine;olanzapine;risperidone	Autism Spectrum Disorder;Schizophrenia

PharmGKB variants

10 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs806368	CNR1	3	2.75	2	methadone;cocaine
rs806374	CNR1		0.00	0
rs806377	CNR1		0.00	0
rs806378	CNR1	3	2.00	1	clozapine;olanzapine;risperidone
rs1049353	CNR1	3	0.75	1	risperidone
rs6454674	CNR1	3	2.50	1	cocaine
rs12720071	CNR1		0.00	0
rs6928499	CNR1	3	2.00	1	opioids
rs806380	CNR1		0.00	0
rs2023239	CNR1	3	2.00	1	opioids

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Cannabinoid receptors

Most potent curated ligand interactions (61 total), top 25:

Ligand	Action	Affinity	Parameter
monlunabant	Inverse agonist	10.68	pIC50
[3H]HU-243	Full agonist	10.4	pKd
HU-210	Full agonist	10.2	pKi
MDMB-Fubinaca	Agonist	10.01	pKi
[3H]rimonabant	Antagonist	10.0	pKd
AM11542	Agonist	9.96	pKi
[123I]AM251	Antagonist	9.6	pKd
taranabant	Inverse agonist	9.52	pKi
JD5037	Antagonist	9.46	pKi
[3H]CP55940	Full agonist	9.4	pKd
CP55940	Full agonist	9.2	pKi
otenabant	Inverse agonist	9.15	pKi
PF-514273	Antagonist	9.09	pKi
AM841	Agonist	8.94	pKi
arachidonyl-2-chloroethylamide	Full agonist	8.9	pKi
WIN55212-2	Full agonist	8.7	pKi
arachidonylcyclopropylamide	Full agonist	8.7	pKi
rimonabant	Antagonist	8.7	pKi
MRI-1867	Inverse agonist	8.64	pKi
selonabant	Antagonist	8.64	pKi
AM7499	Agonist	8.62	pKi
levonantradol	Agonist	8.54	pKi
O-1812	Full agonist	8.5	pKi
AM6545	Antagonist	8.48	pKi
surinabant	Antagonist	8.46	pKi

Binding affinities (BindingDB)

1230 measured of 2864 human assays (2868 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4873473	EC50	0.02 nM
CHEMBL4872695	EC50	0.08 nM
dibenzothiazepine, 12e	KI	0.2 nM
dibenzothiazepine, 12h	KI	0.2 nM
4-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-1-phenylcyclohexane-1-carboxamide	KI	0.28 nM	US-9187480: Peripherally restricted diphenyl purine derivatives
dibenzothiazepine, 12b	KI	0.32 nM
5-(4-chloro-3-methyl-phenyl)-1-(4-methyl-benzyl)-1H-pyrazole-3-carboxylic acid (1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yl)-amide	KI	0.4 nM
(R)-3-(1,1-Dimethyl-heptyl)-9-hydroxymethyl-6,6-dimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-ol	KI	0.41 nM
6-[(4-chlorophenyl)-(4-methoxyphenyl)methyl]-N-(1-phenylpiperidin-4-yl)quinazolin-4-amine	EC50	0.5 nM	US-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
pyrazolopyrimidinone-based antagonist, 3	KI	0.6 nM
1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl]-4-(ethylamino)piperidine-4-carboxamide	KI	0.7 nM
lactam-based compound, 12i	KI	0.7 nM
ether-based lactam, 19e	EC50	0.7 nM
dibenzothiazepine, 12c	KI	0.79 nM
PF-514273	EC50	0.82 nM
5-[bis(4-chlorophenyl)methyl]-2-cyclopropyl-3-[1-(2-methoxyphenyl)sulfonylpiperidin-4-yl]indazole	EC50	1 nM	US-9682940: Indazole derivatives useful as CB-1 inverse agonists
4-[[6-[bis(4-chlorophenyl)methyl]quinazolin-4-yl]amino]-1-phenylcyclohexan-1-ol	EC50	1 nM	US-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
6-[bis(4-fluorophenyl)methyl]-N-(1-phenylpiperidin-4-yl)quinazolin-4-amine	EC50	1 nM	US-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
5,6-bis-(4-bromo-phenyl)-pyrazine-2-carboxylicacid piperidin-1-ylamide	IC50	1 nM
CAS_22475030	KI	1 nM
6-[bis(4-chlorophenyl)methyl]-4-[[1-(trifluoromethylsulfonyl)piperidin-4-yl]amino]-3,4,4a,5,6,7,8,8a-octahydro-1H-quinolin-2-one	EC50	1.2 nM	US-9266835: Quinoline derivatives useful as CB-1 inverse agonists
dibenzothiazepine, 12j	KI	1.2 nM
ether-based lactam, 19b	KI	1.3 nM
2-((1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl)-5-(2-methyloctan-2-yl)phenol	KD	1.3 nM
ether-based lactam, 19c	EC50	1.5 nM
N-[1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]piperidin-4-yl]cyclopentanecarboxamide	KI	1.54 nM	US-9187480: Peripherally restricted diphenyl purine derivatives
dibenzothiazepine, 12k	KI	1.6 nM
lactam-based compound, 12h	KI	1.7 nM
N-[1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]piperidin-4-yl]-2-cyclohexylacetamide	KI	1.93 nM	US-9187480: Peripherally restricted diphenyl purine derivatives
5-[bis(4-methoxyphenyl)methyl]-3-[1-(trifluoromethylsulfonyl)piperidin-4-yl]-2H-indazole	EC50	2 nM	US-9682940: Indazole derivatives useful as CB-1 inverse agonists
5-[4-[5-[bis(4-chlorophenyl)methyl]-2-cyclopropylindazol-3-yl]piperidin-1-yl]sulfonyl-2-methoxybenzoic acid	EC50	2 nM	US-9682940: Indazole derivatives useful as CB-1 inverse agonists
5-[4-[5-[bis(4-chlorophenyl)methyl]-2-cyclopropylindazol-3-yl]piperidin-1-yl]sulfonyl-2-chlorobenzoic acid	EC50	2 nM	US-9682940: Indazole derivatives useful as CB-1 inverse agonists
6-[bis(4-chlorophenyl)methyl]-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]quinazolin-4-amine	EC50	2 nM	US-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
6-[bis(4-chlorophenyl)methyl]-N-(1-pyrimidin-2-ylpiperidin-4-yl)quinazolin-4-amine	EC50	2 nM	US-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
6-[bis(4-chlorophenyl)methyl]-N-(1-phenylpiperidin-4-yl)quinazolin-4-amine	EC50	2 nM	US-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
6-[bis(4-chlorophenyl)methyl]-N-(1-pyridin-2-ylpiperidin-4-yl)quinazolin-4-amine	EC50	2 nM	US-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
ethyl 4-[4-[[6-[bis(4-chlorophenyl)methyl]quinazolin-4-yl]amino]piperidin-1-yl]-4-oxobutanoate	EC50	2 nM	US-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
6-[bis(4-chlorophenyl)methyl]-N-[1-(2-fluorophenyl)sulfonylpiperidin-4-yl]quinazolin-4-amine	EC50	2 nM	US-9682955: Quinazoline derivatives useful as CB-1 inverse agonists
CAS_10391336	KI	2 nM
N-[1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]piperidin-4-yl]-2-cyclopentylacetamide	KI	2.02 nM	US-9187480: Peripherally restricted diphenyl purine derivatives
CHEMBL2087110	KI	2.03 nM
N-(piperidin-1-yl)-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-1H-pyrazole-3-carboxamide	KI	2.3 nM
8-(2-chlorophenyl)-9-(4-chlorophenyl)-6-(piperidin-1-yl)-9H-purine	KI	2.3 nM
2-(3,5-dichlorophenyl)-5-(2-thiophen-2-ylpropan-2-yl)benzene-1,3-diol	KI	2.33 nM	US-9139546: Tri-aryl/heteroaromatic cannabinoids and use thereof
5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide	KD	2.5 nM
lactam-based compound, 12c	KI	2.5 nM
lactam-based compound, 12d	KI	2.5 nM
N-[1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]piperidin-4-yl]benzamide	KI	2.55 nM	US-9187480: Peripherally restricted diphenyl purine derivatives
N-[1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]piperidin-4-yl]-4-methylpentanamide	KI	2.67 nM	US-9187480: Peripherally restricted diphenyl purine derivatives
8-(2-chlorophenyl)-9-(4-chlorophenyl)-6-(4-methylpiperazin-1-yl)-9H-purine	KI	2.8 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL4062749
10.70	EC50	0.02	nM	CHEMBL4873473
10.70	EC50	0.02	nM	CHEMBL4847866
10.57	Ki	0.027	nM	CHEMBL4062749
10.52	Ki	0.03	nM	CHEMBL2063237
10.52	EC50	0.03	nM	CHEMBL4169198
10.40	Ki	0.04	nM	CHEMBL2063236
10.40	EC50	0.04	nM	CHEMBL4862304
10.40	EC50	0.04	nM	CHEMBL4875720
10.30	Ki	0.05	nM	CHEMBL2063239
10.30	EC50	0.05	nM	CHEMBL4846759
10.22	EC50	0.06	nM	CHEMBL4865162
10.22	Ki	0.06	nM	CHEMBL307696
10.21	Ki	0.062	nM	CHEMBL4095223
10.18	Ki	0.066	nM	CHEMBL6145420
10.15	Ki	0.07	nM	CHEMBL2063240
10.15	EC50	0.07	nM	CHEMBL4177060
10.10	Ki	0.08	nM	CHEMBL2063246
10.10	Ki	0.08	nM	CHEMBL2063249
10.10	EC50	0.08	nM	CHEMBL4872695
10.06	EC50	0.088	nM	CHEMBL5091754
10.05	Ki	0.09	nM	CHEMBL2063240
10.05	EC50	0.09	nM	CHEMBL4871491
10.03	IC50	0.094	nM	TARANABANT
10.01	EC50	0.098	nM	CHEMBL5081770
10.00	Ki	0.1	nM	CHEMBL425047
10.00	Ki	0.1	nM	CHEMBL204188
10.00	Ki	0.1	nM	CHEMBL4078689
10.00	Ki	0.1	nM	CHEMBL4095223
10.00	Ki	0.1	nM	CHEMBL4100882
10.00	Ki	0.1	nM	CHEMBL4094098
10.00	Ki	0.1	nM	CHEMBL4437741
10.00	IC50	0.1	nM	CHEMBL489438
10.00	Ki	0.1	nM	CHEMBL584889
10.00	Ki	0.1	nM	CHEMBL578969
10.00	IC50	0.1	nM	CHEMBL604904
10.00	Ki	0.1	nM	CHEMBL111724
9.96	Ki	0.11	nM	CHEMBL2063235
9.96	Ki	0.11	nM	CHEMBL2063245
9.96	Ki	0.11	nM	CHEMBL4087520
9.96	Ki	0.11	nM	CHEMBL4559193
9.96	IC50	0.11	nM	CHEMBL594526
9.96	IC50	0.11	nM	CHEMBL605109
9.96	EC50	0.11	nM	RIMONABANT
9.92	Ki	0.12	nM	CHEMBL2063244
9.92	Ki	0.12	nM	CHEMBL2063245
9.92	Ki	0.12	nM	OTENABANT
9.92	Ki	0.12	nM	CHEMBL1801350
9.90	Kd	0.1259	nM	IBIPINABANT
9.90	Ki	0.1259	nM	CHEMBL4087520

PubChem BioAssay actives

2493 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.

Compound	Assay	Type	Value	Unit
12-chloro-3-(2,4-dichlorophenyl)-N-piperidin-1-yl-3,4-diazatricyclo[8.4.0.02,6]tetradeca-1(10),2(6),4,11,13-pentaene-5-carboxamide	328661: Binding affinity to CB1 receptor	ki	<0.0001	uM
N-[2-(2-chlorophenyl)-3-(4-chlorophenyl)-5,6,7,8-tetrahydrooxepino[3,2-c]pyrazol-8-yl]-2-methylpropanamide	673842: Antagonist activity at human CB1 receptor expressed in CHO-K1 cells assessed as inhibition of CP-55940-induced [35S]GTPgammaS binding incubated for 10 mins prior to CP-55940-challenge measured after 1 hr by beta counting	ki	<0.0001	uM
(4Z,7Z)-N-cyclopropyl-9-[3-[(2Z,5Z,8Z)-undeca-2,5,8-trienyl]oxiran-2-yl]nona-4,7-dienamide	1350536: Agonist activity at N-terminal FLAG-tagged human CB1 receptor transfected in human HTLA cells assessed as induction of beta-arrestin-recruitment after 8 to 14 hrs by bright-glo luminescence based assay	ec50	<0.0001	uM
3-pyrazin-2-yl-N-[1-(trifluoromethyl)cyclobutyl]-11-oxa-3,4-diazatricyclo[6.2.1.02,6]undeca-2(6),4-diene-5-carboxamide	1768789: Agonist activity at human CB1 receptor expressed in CHO-K1 cells assessed as increase in cAMP level incubated for 20 mins measured after 60 mins addition of cAMP detect reagent by HTRF analysis	ec50	<0.0001	uM
5-[3-(2-methylbutan-2-yl)-1,2,4-oxadiazol-5-yl]-3-pyrazin-2-yl-11-oxa-3,4-diazatricyclo[6.2.1.02,6]undeca-2(6),4-diene	1768789: Agonist activity at human CB1 receptor expressed in CHO-K1 cells assessed as increase in cAMP level incubated for 20 mins measured after 60 mins addition of cAMP detect reagent by HTRF analysis	ec50	<0.0001	uM
1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-4-(ethylamino)piperidine-4-carboxamide	411328: Antagonist activity against human CB1 receptor expressed in CHO-K1 cells by [35S]GTPgamma binding assay	ki	0.0001	uM
5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-[1-(2-phenylpropan-2-yl)imidazol-4-yl]pyrazole	446736: Antagonist activity at human CB1 receptor transfected in CHO-K1cells by GTPgamma[35S] binding assay	ki	0.0001	uM
5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-piperidin-1-ylpyrazole-3-carboxamide	464691: Inverse agonist activity at human cannabinoid CB1 receptor expressed in CHO cells assessed as inhibition of forskolin-stimulated cAMP accumulation after 60 mins	ec50	0.0001	uM
2-[(1R,2R,5R)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol	464691: Inverse agonist activity at human cannabinoid CB1 receptor expressed in CHO cells assessed as inhibition of forskolin-stimulated cAMP accumulation after 60 mins	ic50	0.0001	uM
9-(hydroxymethyl)-6,6-dimethyl-3-(2-methyloctan-2-yl)benzo[c]chromen-1-ol	49315: Binding affinity was determined for Cannabinoid receptor 1	ki	0.0001	uM
N-[(2S,3S)-4-(4-chlorophenyl)-3-(3-cyanophenyl)butan-2-yl]-2-methyl-2-[[5-(trifluoromethyl)-2-pyridinyl]oxy]propanamide	318864: Displacement of [3H]SR-141716 from human wild type CB1R expressed in CHO cells	ic50	0.0001	uM
2-(2-chlorophenyl)-3-(4-chlorophenyl)-6-(2,2,2-trifluoroethyl)pyrazolo[4,3-d]pyrimidin-7-one	260297: Functional activity at human CB1 receptor transfected in CHOK1 cells by [35SGTP]gammaS assay	ki	0.0001	uM
2-(2-chlorophenyl)-3-(4-chlorophenyl)-6-(2,2-difluoropropyl)pyrazolo[4,3-d]pyrimidin-7-one	260297: Functional activity at human CB1 receptor transfected in CHOK1 cells by [35SGTP]gammaS assay	ki	0.0001	uM
[4-[2-(2,4-dichlorophenyl)-5-methyl-4-(piperidin-1-ylcarbamoyl)imidazol-1-yl]phenyl] 3,3,3-trifluoropropane-1-sulfonate	1467903: Displacement of [3H]CP55940 from recombinant human CB1 receptor expressed in beta-galactosidase expressing CHOK1 cell membranes after 60 mins by scintillation spectrometry	ki	0.0001	uM
[4-[2-(2,4-dichlorophenyl)-5-methyl-4-(piperidin-1-ylcarbamoyl)imidazol-1-yl]phenyl] 4,4,4-trifluorobutane-1-sulfonate	1467903: Displacement of [3H]CP55940 from recombinant human CB1 receptor expressed in beta-galactosidase expressing CHOK1 cell membranes after 60 mins by scintillation spectrometry	ki	0.0001	uM
[4-[2-(2,4-dichlorophenyl)-5-methyl-4-[[5-(trifluoromethyl)-2-pyridinyl]carbamoyl]imidazol-1-yl]phenyl] 3,3,3-trifluoropropane-1-sulfonate	1467903: Displacement of [3H]CP55940 from recombinant human CB1 receptor expressed in beta-galactosidase expressing CHOK1 cell membranes after 60 mins by scintillation spectrometry	ki	0.0001	uM
[4-[2-(2,4-dichlorophenyl)-5-methyl-4-(piperidin-1-ylcarbamoyl)imidazol-1-yl]phenyl] butane-1-sulfonate	1467903: Displacement of [3H]CP55940 from recombinant human CB1 receptor expressed in beta-galactosidase expressing CHOK1 cell membranes after 60 mins by scintillation spectrometry	ki	0.0001	uM
1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methyl-3-[1-(2-phenylpropan-2-yl)imidazol-4-yl]pyrazole	446736: Antagonist activity at human CB1 receptor transfected in CHO-K1cells by GTPgamma[35S] binding assay	ki	0.0001	uM
N-[2-(2-chlorophenyl)-3-(4-chlorophenyl)-5,6,7,8-tetrahydrooxepino[3,2-c]pyrazol-8-yl]propanamide	673842: Antagonist activity at human CB1 receptor expressed in CHO-K1 cells assessed as inhibition of CP-55940-induced [35S]GTPgammaS binding incubated for 10 mins prior to CP-55940-challenge measured after 1 hr by beta counting	ki	0.0001	uM
propan-2-yl N-[2-(2-chlorophenyl)-3-(4-chlorophenyl)-5,6,7,8-tetrahydrooxepino[3,2-c]pyrazol-8-yl]carbamate	673842: Antagonist activity at human CB1 receptor expressed in CHO-K1 cells assessed as inhibition of CP-55940-induced [35S]GTPgammaS binding incubated for 10 mins prior to CP-55940-challenge measured after 1 hr by beta counting	ki	0.0001	uM
1-[2-(2-chlorophenyl)-3-(4-chlorophenyl)-5,6,7,8-tetrahydrooxepino[3,2-c]pyrazol-8-yl]-3-ethylurea	673839: Displacement of [3H]SR141716A form human CB1 receptor expressed in HEK293 cells after 60 mins by beta counting	ki	0.0001	uM
(4Z,7Z)-N-(1-hydroxypropan-2-yl)-9-[3-[(2Z,5Z,8Z)-undeca-2,5,8-trienyl]oxiran-2-yl]nona-4,7-dienamide	1350536: Agonist activity at N-terminal FLAG-tagged human CB1 receptor transfected in human HTLA cells assessed as induction of beta-arrestin-recruitment after 8 to 14 hrs by bright-glo luminescence based assay	ec50	0.0001	uM
N-(3-pentyl-1,3-benzothiazol-2-ylidene)adamantane-1-carboxamide	1569940: Displacement of [3H]CP55940 from recombinant human CB1R expressed in HEK293 cell membranes incubated for 90 mins by Cheng-Prusoff equation analysis	ki	0.0001	uM
N-(3-pentyl-1,3-benzothiazol-2-ylidene)naphthalene-1-carboxamide	1569940: Displacement of [3H]CP55940 from recombinant human CB1R expressed in HEK293 cell membranes incubated for 90 mins by Cheng-Prusoff equation analysis	ki	0.0001	uM
[4-[2-(2,4-dichlorophenyl)-4-[(6-fluoro-3-pyridinyl)carbamoyl]-5-methylimidazol-1-yl]phenyl] 3,3,3-trifluoropropane-1-sulfonate	1467903: Displacement of [3H]CP55940 from recombinant human CB1 receptor expressed in beta-galactosidase expressing CHOK1 cell membranes after 60 mins by scintillation spectrometry	ki	0.0001	uM
2-(2-chlorophenyl)-1-(4-chlorophenyl)-5-ethyl-N-piperidin-1-ylimidazole-4-carboxamide	443600: Antagonist activity at human CB1 receptor expressed in CHO cells assessed as inhibition of [3H]arachidonic acid release	kd	0.0002	uM
7-[(6aR,10aR)-1-hydroxy-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-3-yl]-7-methyloctanenitrile	311037: Binding affinity to CB1 receptor	ki	0.0002	uM
2-(2,4-dichlorophenyl)-5-methyl-N-piperidin-1-yl-1-[4-(4,4,4-trifluorobutoxy)phenyl]imidazole-4-carboxamide	1467903: Displacement of [3H]CP55940 from recombinant human CB1 receptor expressed in beta-galactosidase expressing CHOK1 cell membranes after 60 mins by scintillation spectrometry	ki	0.0002	uM
[4-[2-(2,4-dichlorophenyl)-5-methyl-4-(piperidin-1-ylcarbamoyl)imidazol-1-yl]phenyl] 3-methylbutane-1-sulfonate	1467903: Displacement of [3H]CP55940 from recombinant human CB1 receptor expressed in beta-galactosidase expressing CHOK1 cell membranes after 60 mins by scintillation spectrometry	ki	0.0002	uM
(4Z,7Z)-N-(3-hydroxypropyl)-9-[3-[(2Z,5Z,8Z)-undeca-2,5,8-trienyl]oxiran-2-yl]nona-4,7-dienamide	1350536: Agonist activity at N-terminal FLAG-tagged human CB1 receptor transfected in human HTLA cells assessed as induction of beta-arrestin-recruitment after 8 to 14 hrs by bright-glo luminescence based assay	ec50	0.0002	uM
N-[1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]piperidin-4-yl]-3,3-dimethylbutanamide	1588558: Displacement of [3H]-CP55940 from human CB1 receptor expressed in CHO cell membranes	ki	0.0002	uM
N-butyl-6-(4-chlorophenyl)benzo[b][1,4]benzothiazepine-3-carboxamide	1798964: CB Receptor Radioligand Binding Assay (Ki) from Article 10.1021/jm801534c: “Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists.”	ki	0.0002	uM
(6aR,10aR)-3-(2-hexyl-1,3-dithiolan-2-yl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol	303924: Binding affinity at CB1 receptor	ki	0.0003	uM
N-[4-(4-chlorophenyl)-3-(3-cyanophenyl)butan-2-yl]-2-methyl-2-[[5-(trifluoromethyl)-2-pyridinyl]oxy]propanamide	352285: Antagonist activity against human recombinant cannabinoid-1 receptor	ic50	0.0003	uM
5-(4-chlorophenyl)-N’-(4-chlorophenyl)sulfonyl-4-phenyl-3,4-dihydropyrazole-2-carboximidamide	49329: Antagonistic activity towards cannabinoid receptor 1 expressed as [3H]Arachidonic acid release in CHO cells	kd	0.0003	uM
[4-[2-(2,4-dichlorophenyl)-5-methyl-4-(piperidin-1-ylcarbamoyl)imidazol-1-yl]phenyl] propane-1-sulfonate	1467903: Displacement of [3H]CP55940 from recombinant human CB1 receptor expressed in beta-galactosidase expressing CHOK1 cell membranes after 60 mins by scintillation spectrometry	ki	0.0003	uM
(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-carboxamide	1175746: Agonist activity at human recombinant CB1 receptor expressed in CHOK1 cells assessed as cAMP accumulation by HTRF method	ec50	0.0003	uM
methyl N-[2-(2-chlorophenyl)-3-(4-chlorophenyl)-5,6,7,8-tetrahydrooxepino[3,2-c]pyrazol-8-yl]carbamate	673839: Displacement of [3H]SR141716A form human CB1 receptor expressed in HEK293 cells after 60 mins by beta counting	ki	0.0003	uM
(4-methoxyphenyl)-[1-(morpholin-4-ylmethyl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-4-yl]methanone	383283: Agonist activity at CB1 receptor	ic50	0.0003	uM
3-[1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]piperidin-4-yl]-1-(2-methoxyethyl)-1-methylurea	1567036: Displacement of [3H]CP55940 from human CB1 receptor expressed in HEK293 cell membranes	ki	0.0003	uM
N-[(2S)-1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butylindazole-3-carboxamide	1853934: Displacement of [3H]-CP55940 from human CB1 receptor expressed in human HEK293-EBNA cells incubated for 60 mins by radioligand competitive binding assay based liquid scintillation counter	ki	0.0003	uM
1-(2,4-dichlorophenyl)-N-piperidin-1-yl-4-[(pyrrolidin-1-ylsulfonylamino)methyl]-5-[5-[2-[4-(trifluoromethyl)phenyl]ethynyl]thiophen-2-yl]pyrrole-3-carboxamide	1645904: Antagonist activity at human cannabinoid CB1 receptor	ki	0.0003	uM
3-[6-(2-chlorophenyl)-5-(4-chlorophenyl)-2-(2,2-dimethylpropanoyl)furo[2,3-b]pyridin-3-yl]-1,1-dimethylurea	476812: Inhibition of human CB1 receptor	ic50	0.0004	uM
(6aR,10aR)-3-(1-hexylcyclopropyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol	303924: Binding affinity at CB1 receptor	ki	0.0004	uM
(6aR,10aR)-3-(6-bromo-2-methylhexan-2-yl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol	311037: Binding affinity to CB1 receptor	ki	0.0004	uM
(6aR,10aR)-3-(1-hexylcyclopentyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydrobenzo[c]chromen-1-ol	303924: Binding affinity at CB1 receptor	ki	0.0004	uM
5-(4-chlorophenyl)-4-phenyl-N’-(2,4,6-trimethylphenyl)sulfonyl-3,4-dihydropyrazole-2-carboximidamide	49329: Antagonistic activity towards cannabinoid receptor 1 expressed as [3H]Arachidonic acid release in CHO cells	kd	0.0004	uM
5-(4-chlorophenyl)-N’-methyl-4-phenyl-N-(2,4,6-trimethylphenyl)sulfonyl-3,4-dihydropyrazole-2-carboximidamide	49329: Antagonistic activity towards cannabinoid receptor 1 expressed as [3H]Arachidonic acid release in CHO cells	kd	0.0004	uM
methyl (2S)-2-[[1-(5-fluoropentyl)indole-3-carbonyl]amino]-3,3-dimethylbutanoate	2095059: Agonist activity at HA-tagged human CB1 receptor stably transfected in AtT20 cells incubated for 60 mins by FLIPR membrane potential assay	ec50	0.0004	uM
N-[1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]piperidin-4-yl]-2-fluorobenzenesulfonamide	1588558: Displacement of [3H]-CP55940 from human CB1 receptor expressed in CHO cell membranes	ki	0.0004	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol	decreases secretion, affects cotreatment, decreases reaction, increases reaction, increases abundance (+5 more)	31
Dronabinol	affects reaction, affects response to substance, affects cotreatment, decreases reaction, affects expression (+6 more)	19
Rimonabant	increases reaction, increases abundance, affects reaction, increases activity, increases expression (+4 more)	13
(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone	affects localization, affects reaction, increases activity, decreases reaction, increases degradation (+3 more)	10
1-pentyl-3-(1-naphthoyl)indole	affects binding, decreases reaction, increases activity, increases chemical synthesis, increases reaction	7
Valproic Acid	decreases expression, increases expression	7
Cannabidiol	decreases reaction, affects binding, affects cotreatment, increases reaction, increases expression (+4 more)	6
methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoate	affects binding, decreases reaction, increases reaction, increases activity	4
anandamide	decreases reaction, increases activity, affects activity, affects localization, increases reaction (+2 more)	4
4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone	decreases reaction, increases reaction, affects binding, increases activity	4
Colforsin	affects response to substance, affects cotreatment, increases expression, affects binding, decreases reaction (+2 more)	4
1-pentyl-1H-indole-3-carboxylic acid 8-quinolinyl ester	decreases reaction, increases activity, increases chemical synthesis, increases reaction, affects binding	3
1-(5-fluoropentyl)-3-(4-methyl-1-naphthoyl)indole	affects binding, decreases reaction, increases activity, increases chemical synthesis, increases reaction	3
N-(1-adamantyl)-1-pentylindazole-3-carboxamide	affects binding, decreases reaction, increases activity, increases chemical synthesis, increases expression	3
(4-ethyl-1-naphthalenyl)(1-(5-fluoropentyl)-1H-indol-3-yl)methanone	affects binding, decreases reaction, increases activity, increases chemical synthesis, increases reaction	3
AB-FUBINACA	affects binding, increases activity, decreases reaction	3
5F-ADB cannabinoid	decreases reaction, affects binding, increases activity, decreases expression	3
HU 211	increases response to substance, affects binding, increases activity, decreases reaction	3
(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone	affects binding, increases activity, decreases reaction, increases chemical synthesis, increases reaction	3
Cyclic AMP	affects binding, decreases reaction, increases activity, increases chemical synthesis, increases abundance	3
Cocaine	affects response to substance	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Guanosine 5’-O-(3-Thiotriphosphate)	affects binding, increases reaction	3
Pertussis Toxin	decreases reaction, increases activity	3
N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide	affects binding, increases activity, decreases reaction	2
N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide	affects binding, increases activity	2
N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide	affects binding, decreases reaction, increases activity, increases chemical synthesis	2
N-(1-(aminocarbonyl)-2-methylpropyl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide	affects binding, increases activity	2
methyl 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate	affects binding, increases activity, decreases reaction	2
2-(4-methoxyphenyl)-1-(1-pentyl-indol-3-yl)methanone	increases activity, decreases reaction, increases chemical synthesis, affects binding	2

ChEMBL screening assays

1559 unique, capped per target: 985 binding, 524 functional, 47 admet, 3 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1838787	Binding	Binding affinity to CB receptor in human cortex membranes	Conformationally constrained analogs of BAY 59-3074 as novel cannabinoid receptor ligands. — Bioorg Med Chem Lett
CHEMBL5364352	Functional	Agonist 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 analysis	Cannabidiol Analogue CIAC001 for the Treatment of Morphine-Induced Addiction by Targeting PKM2. — J Med Chem
CHEMBL3866931	ADMET	Displacement of [3H]-CP-55940 from human CB1 receptor expressed in HEK293 cell membranes after 90 mins by radioligand binding assay	Discovery of novel Tetrahydrobenzo[b]thiophene and pyrrole based scaffolds as potent and selective CB2 receptor ligands: The structural elements controlling binding affinity, selectivity and functionality. — Eur J Med Chem

Cellosaurus cell lines

20 cell lines: 7 transformed cell line, 7 spontaneously immortalized cell line, 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0SB	ACTOne CB1	Transformed cell line	Female
CVCL_E0AG	Ubigene HeLa CNR1 KO	Cancer cell line	Female
CVCL_E4J0	Genomeditech CHO-K1 H_CNR1(CB1)	Spontaneously immortalized cell line	Female
CVCL_E6TT	Genomeditech HEK-293 H_CNR1(CB1)	Transformed cell line	Female
CVCL_F1TG	HyCyte SH-SY5Y KO-hCNR1	Cancer cell line	Female
CVCL_F2AK	CHO-K1 (+Galpha16) AequoScreen Cannabinoid CB1	Spontaneously immortalized cell line	Female
CVCL_H409	CHO-K1/CB1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KU95	cAMP Hunter CHO-K1 CNR1 Gi	Spontaneously immortalized cell line	Female
CVCL_KW72	PathHunter CHO-K1 CNR1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_SJ42	HAP1 CNR1 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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