OPRK1

Summary

OPRK1 (opioid receptor kappa 1, HGNC:8154) is a protein-coding gene on chromosome 8q11.23, encoding Kappa-type opioid receptor (P41145). G-protein coupled opioid receptor that functions as a receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins.

This gene encodes an opioid receptor, which is a member of the 7 transmembrane-spanning G protein-coupled receptor family. It functions as a receptor for endogenous ligands, as well as a receptor for various synthetic opioids. Ligand binding results in inhibition of adenylate cyclase activity and neurotransmitter release. This opioid receptor plays a role in the perception of pain and mediating the hypolocomotor, analgesic and aversive actions of synthetic opioids. Variations in this gene have also been associated with alcohol dependence and opiate addiction. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon.

Source: NCBI Gene 4986 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 23 total
• Druggable target: yes — 344 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000912

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8154
Approved symbol	OPRK1
Name	opioid receptor kappa 1
Location	8q11.23
Locus type	gene with protein product
Status	Approved
Aliases	KOR, OPRK
Ensembl gene	ENSG00000082556
Ensembl biotype	protein_coding
OMIM	165196
Entrez	4986

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000265572, ENST00000520287, ENST00000522508, ENST00000524278, ENST00000673285

RefSeq mRNA: 3 — MANE Select: NM_000912 NM_000912, NM_001282904, NM_001318497

CCDS: CCDS6152, CCDS64895, CCDS94292

Canonical transcript exons

ENST00000265572 — 4 exons

Exon	Start	End
ENSE00001246898	53250781	53251085
ENSE00002139173	53225724	53229829
ENSE00003556810	53234759	53235111
ENSE00003842815	53251448	53251637

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 84.82.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4608 / max 29.1148, expressed in 197 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93067	0.2379	132
93066	0.1140	70
93068	0.1089	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	84.82	gold quality
pons	UBERON:0000988	83.69	gold quality
lateral nuclear group of thalamus	UBERON:0002736	83.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	75.54	gold quality
entorhinal cortex	UBERON:0002728	71.09	gold quality
middle temporal gyrus	UBERON:0002771	70.35	gold quality
nucleus accumbens	UBERON:0001882	69.64	gold quality
dorsal root ganglion	UBERON:0000044	69.52	gold quality
prefrontal cortex	UBERON:0000451	66.40	gold quality
temporal lobe	UBERON:0001871	64.68	gold quality
superior frontal gyrus	UBERON:0002661	64.46	gold quality
placenta	UBERON:0001987	63.59	gold quality
cingulate cortex	UBERON:0003027	63.41	gold quality
frontal cortex	UBERON:0001870	63.39	gold quality
anterior cingulate cortex	UBERON:0009835	63.19	gold quality
neocortex	UBERON:0001950	63.02	gold quality
primary visual cortex	UBERON:0002436	63.01	gold quality
hypothalamus	UBERON:0001898	62.86	gold quality
trigeminal ganglion	UBERON:0001675	62.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	62.31	gold quality
caudate nucleus	UBERON:0001873	62.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	62.05	gold quality
cerebral cortex	UBERON:0000956	61.56	gold quality
telencephalon	UBERON:0001893	61.46	gold quality
amygdala	UBERON:0001876	61.40	gold quality
postcentral gyrus	UBERON:0002581	61.15	silver quality
parietal lobe	UBERON:0001872	60.52	silver quality
paraflocculus	UBERON:0005351	60.04	silver quality
occipital lobe	UBERON:0002021	59.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.42
E-MTAB-5061	no	3.15

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MAX, MXD1, MYC, SP1

miRNA regulators (miRDB)

181 targeting OPRK1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-381-3P	99.93	71.87	2854

Literature-anchored findings (GeneRIF, showing 40)

• These results suggest that oligomerization of chemokine receptor CCR5 and opioid receptors mu, delta and kappa on the cell membrane of human or monkey lymphocytes may modulate receptor functions. (PMID:12413885)
• phosphorylation of serine 369 mediates KOR desensitization and internalization (PMID:12815037)
• binding of the KOR to NHERF-1/EBP50 facilitates oligomerization of NHERF-1/EBP50, leading to stimulation of NHE3. (PMID:15070904)
• OPKR1 structure and association of haplotypes with opiate addiction was found to have empirical significance. (PMID:15608558)
• The diterpenoid salvinorin A utilizes unique residues within a commonly shared binding pocket to selectively activate KORs. (PMID:15952771)
• investigation of the ability of different opioid receptors to regulate the phosphorylation and degradation of tuberin (PMID:16053916)
• Results describe the residues of the transmembrane helices 7 of delta and kappa opioid receptors that are on the water-accessible surface of the binding-site crevices. (PMID:16331961)
• GEC1 interacts with the kappa opioid receptor and enhances expression of the receptor (PMID:16431922)
• Family-based analyses demonstrated associations between alcohol dependence and multiple SNPs in intron 2 of OPRK1. (PMID:16924269)
• Helical orientation of helix 2 are critical for the selectivity of salvinorin A binding to KOR and provide a structurally novel basis for ligand selectivity. (PMID:17121830)
• The kappa opioid receptor (KOR) system seems to play a role in stress responsivity, opiate withdrawal and responses to psycho-stimulants, inhibiting mesolimbic dopamine. (PMID:17373729)
• frequency of KOR 36G > T SNP was significantly higher among heroin-dependent individuals compared with control subjects (PMID:17373729)
• activation of KORs alters functional properties of neural precursor cells that are relevant to human brain development and repair. (PMID:17538007)
• There is a positive haplotypic association between OPRK1 variants and alcohol dependence in European Americans. (PMID:17622222)
• long duration KOR antagonists disrupt KOR signaling by activating JNK (PMID:17702750)
• Thus, N-glycosylation of the hKOR plays important roles in stability and trafficking along the biosynthesis pathway of the receptor protein as well as agonist-induced receptor regulation. (PMID:17711303)
• genes encoding the mu-, delta-, and kappa-opioid receptors may contribute to variation in personality traits (PMID:18213616)
• Family-based association analyses detected evidence of association of an insertion in the ORK1 gene with alcoholism. (PMID:18319328)
• Show that LPK-26 is a novel selective kappa-opioid receptor agonist with highly potent antinociception effects and low physical dependence potential. (PMID:18353307)
• response to nalmefene did not vary with genotype (PMID:18537939)
• the coexpression of KOR-SA35443 (kappa opioid receptor) and NG2(chondroitin sulfate proteoglycan) in result of karyotype abnormal changes may predict a poor prognosis in Pro-B acute lymphoblastic leukemia (PMID:18767415)
• Neither pressure pain threshold nor tolerance between major and minor alleles of other SNPs of the OPRM1, OPRK1, and OPRD1 genes were significantly different suggesting an association between the IVS2+31G>A SNP of OPRM1 gene and pressure pain sensitivity. (PMID:19032295)
• Review. kappa-Opioid receptor signaling and brain reward function. (PMID:19804796)
• because of its stronger binding for hKOPR, GEC1 is able to be recruited by hKOPR sufficiently without membrane association via its C-terminal modification; however, du GABARAP appears to require C-terminal modifications to enhance KOPR expression. (PMID:21388957)
• This is the first report detailing the initiation of a KOR-induced JAK2/STAT3 and IRF2 signaling cascade, and these pathways result in substantial down-regulation of CXCR4 expression. (PMID:21447649)
• These findings provide evidence that previously demonstrated KOR-mediated reduction in intraocular pressure could be caused, in part, by NO production in both the ciliary body and the trabecular meshwork. (PMID:21666232)
• In summary, this study provides evidence that gene-gene interaction between KOR and OPRM1 can influence the risk of addiction to narcotics and alcohol. (PMID:22138325)
• Human apelin forms a heterodimer with the kappa opioid receptor and leads to increased protein kinase C and decreased protein kinase A. (PMID:22200678)
• crystal structure of the human kappa-OR in complex with the selective antagonist JDTic, arranged in parallel dimers, at 2.9 A resolution (PMID:22437504)
• Pairwise tag single nucleotide polymorphisms (SNPs) in DREAM, PDYN and OPRK1 were genotyped in a United Kingdom population-based discovery cohort in whom pain was assessed. (PMID:22730276)
• delta and mu-opioid receptors, but not kappa-opioid receptors, are functional in the neuronally stimulated longitudinal human vas deferens (PMID:22752269)
• A role is estsablished for dynorphin kappa-opioid receptor signaling in fear extinction. (PMID:22764240)
• Data indicate that 14-3-3zeta interaction with kappa-opioid receptor (hKOPR) C-tail promotes export of hKOPR. (PMID:22989890)
• hKOR activates p38 MAPK through a phosphorylation and arrestin-dependent mechanism; however, activation differs between hKOR and rKOR for some ligands (PMID:23086943)
• This study supports a role for NTRK2 and OPRK1 signaling in the pathophysiology of mood disorder. (PMID:23277131)
• OPRK1 and PDYN polymorphisms may alter severity of HIV infection and response to treatment. (PMID:23392455)
• Kappa Opioid receptor in the nucleus is a novel prognostic factor of esophageal squamous cell carcinoma. (PMID:23574786)
• OPRK1 rs6989250 C>G is associated with stress-induced craving and cortisol, hyperactive hypothalamus/thalamus-midbrain-cerebellum responses, and also associated with greater subsequent cocaine relapse risk. (PMID:23962922)
• This study indicates that a patient’s OPRK1 genotype could be used to identify a subset of individuals for whom vaccine treatment may be an effective pharmacotherapy for cocaine dependence. (PMID:23995774)
• crystal structure provides fundamental insights into the activation mechanism of the kappa-opioid receptor and suggest that “functional” residues may be directly involved in transduction of the agonist binding event (PMID:24121503)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	oprk1	ENSDARG00000006894
mus_musculus	Oprk1	ENSMUSG00000025905
rattus_norvegicus	Oprk1	ENSRNOG00000007647
drosophila_melanogaster	Rh7	FBGN0036260
caenorhabditis_elegans	trhr-1	WBGENE00016265

Paralogs (17): OPRM1 (ENSG00000112038), KISS1R (ENSG00000116014), OPRD1 (ENSG00000116329), OPRL1 (ENSG00000125510), NPBWR2 (ENSG00000125522), SSTR4 (ENSG00000132671), SSTR1 (ENSG00000139874), SSTR5 (ENSG00000162009), GPR149 (ENSG00000174948), SSTR2 (ENSG00000180616), UTS2R (ENSG00000181408), PTGDR2 (ENSG00000183134), CMKLR2 (ENSG00000183671), LTB4R (ENSG00000213903), LTB4R2 (ENSG00000213906), SSTR3 (ENSG00000278195), NPBWR1 (ENSG00000288611)

Protein

Protein identifiers

Kappa-type opioid receptor — P41145 (reviewed: P41145)

All UniProt accessions (3): P41145, A0A5F9ZI09, E5RJI5

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled opioid receptor that functions as a receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as a receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.

Subunit / interactions. Interacts with NHERF1. Interacts with GABARAPL1.

Subcellular location. Cell membrane.

Tissue specificity. Detected in brain and placenta.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P41145-1	1	yes
P41145-2	2

RefSeq proteins (3): NP_000903, NP_001269833, NP_001305426 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000452	Kappa_opi_rcpt	Family
IPR001418	Opioid_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (46 total): helix 10, topological domain 8, strand 8, transmembrane region 7, turn 5, glycosylation site 2, chain 1, lipid moiety-binding region 1, disulfide bond 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7UL2	ELECTRON MICROSCOPY	2.4
22ES	ELECTRON MICROSCOPY	2.43
7T10	ELECTRON MICROSCOPY	2.5
8FEG	ELECTRON MICROSCOPY	2.54
8DZR	ELECTRON MICROSCOPY	2.61
8DZS	ELECTRON MICROSCOPY	2.65
7T11	ELECTRON MICROSCOPY	2.7
8DZP	ELECTRON MICROSCOPY	2.71
9V6O	ELECTRON MICROSCOPY	2.76
8DZQ	ELECTRON MICROSCOPY	2.82
22EM	ELECTRON MICROSCOPY	2.86
4DJH	X-RAY DIFFRACTION	2.9
9L60	ELECTRON MICROSCOPY	2.9
9W49	ELECTRON MICROSCOPY	2.9
9MQL	ELECTRON MICROSCOPY	2.96
7UL3	ELECTRON MICROSCOPY	3
8K2W	ELECTRON MICROSCOPY	3
8VVF	ELECTRON MICROSCOPY	3
6B73	X-RAY DIFFRACTION	3.1
7UL5	ELECTRON MICROSCOPY	3.1
9MQK	ELECTRON MICROSCOPY	3.18
8F7W	ELECTRON MICROSCOPY	3.19
6VI4	X-RAY DIFFRACTION	3.3
7Y1F	ELECTRON MICROSCOPY	3.3
7YIT	X-RAY DIFFRACTION	3.3
8VVE	ELECTRON MICROSCOPY	3.3
8VVG	ELECTRON MICROSCOPY	3.3
9UWV	ELECTRON MICROSCOPY	3.3
7YMJ	ELECTRON MICROSCOPY	3.35
9LFA	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41145-F1	80.06	0.49

Antibody-complex structures (SAbDab): 20 — 6B73, 6VI4, 7T10, 7T11, 7UL2, 7UL3, 7UL5, 7Y1F, 7YIT, 7YMJ, 8DZP, 8DZQ, 8DZR, 8DZS, 8F7W, 8FEG, 8HNN, 8K2W, 8VVF, 9V6O

Functional residue map

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

Post-translational modifications (1): 345

Disulfide bonds (1): 131–210

Glycosylation sites (2): 25, 39

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events
R-HSA-9022699	MECP2 regulates neuronal receptors and channels

MSigDB gene sets: 287 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_DIGESTION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_COGNITION, MODULE_274, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_COCAINE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_ADULT_BEHAVIOR, GOBP_ASSOCIATIVE_LEARNING

GO Biological Process (33): immune response (GO:0006955), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), neuropeptide signaling pathway (GO:0007218), chemical synaptic transmission (GO:0007268), sensory perception (GO:0007600), locomotory behavior (GO:0007626), sensory perception of pain (GO:0019233), adenylate cyclase-inhibiting opioid receptor signaling pathway (GO:0031635), response to insulin (GO:0032868), positive regulation of dopamine secretion (GO:0033603), negative regulation of luteinizing hormone secretion (GO:0033685), response to nicotine (GO:0035094), G protein-coupled opioid receptor signaling pathway (GO:0038003), maternal behavior (GO:0042711), eating behavior (GO:0042755), response to estrogen (GO:0043627), estrous cycle (GO:0044849), response to ethanol (GO:0045471), regulation of saliva secretion (GO:0046877), behavioral response to cocaine (GO:0048148), sensory perception of temperature stimulus (GO:0050951), defense response to virus (GO:0051607), cellular response to lipopolysaccharide (GO:0071222), cellular response to glucose stimulus (GO:0071333), positive regulation of p38MAPK cascade (GO:1900745), positive regulation of potassium ion transmembrane transport (GO:1901381), response to acrylamide (GO:1903937), positive regulation of eating behavior (GO:1904000), conditioned place preference (GO:1990708), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), response to cocaine (GO:0042220)

GO Molecular Function (7): G protein-coupled opioid receptor activity (GO:0004985), receptor serine/threonine kinase binding (GO:0033612), dynorphin receptor activity (GO:0038048), neuropeptide binding (GO:0042923), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515), G protein-coupled peptide receptor activity (GO:0008528)

GO Cellular Component (16): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), sarcoplasmic reticulum (GO:0016529), T-tubule (GO:0030315), dendrite (GO:0030425), synaptic vesicle membrane (GO:0030672), presynaptic membrane (GO:0042734), neuron projection (GO:0043005), perikaryon (GO:0043204), axon terminus (GO:0043679), postsynaptic membrane (GO:0045211), sarcolemma (GO:0042383), neuronal cell body (GO:0043025)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Transcriptional Regulation by MECP2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
G protein-coupled receptor signaling pathway	4
G protein-coupled opioid receptor signaling pathway	2
G protein-coupled receptor activity	2
cytoplasm	2
synaptic membrane	2
presynapse	2
immune system process	1
response to stimulus	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
phospholipase C activator activity	1
anterograde trans-synaptic signaling	1
nervous system process	1
behavior	1
sensory perception	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
response to peptide hormone	1
dopamine secretion	1
regulation of dopamine secretion	1
positive regulation of catecholamine secretion	1
luteinizing hormone secretion	1
negative regulation of gonadotropin secretion	1
regulation of luteinizing hormone secretion	1
response to chemical	1
parental behavior	1
feeding behavior	1
response to hormone	1
ovulation cycle	1
response to alcohol	1
regulation of digestive system process	1
saliva secretion	1
regulation of body fluid levels	1
regulation of secretion	1
signaling receptor binding	1
G protein-coupled opioid receptor activity	1
G protein-coupled peptide receptor activity	1
peptide binding	1
transmembrane signaling receptor activity	1
binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

31 interactions, top by confidence:

A	B	Type	Score
APLNR	OPRK1	psi-mi:“MI:0403”(colocalization)	0.650
APLNR	OPRK1	psi-mi:“MI:0915”(physical association)	0.650
OPRK1	APLNR	psi-mi:“MI:2364”(proximity)	0.650
OPRK1	APLNR	psi-mi:“MI:0915”(physical association)	0.650
OPRK1	GABARAPL1	psi-mi:“MI:0915”(physical association)	0.630
GABARAPL1	OPRK1	psi-mi:“MI:0915”(physical association)	0.630
OPRK1	GABARAPL1	psi-mi:“MI:0407”(direct interaction)	0.630
OPRK1	NKG7	psi-mi:“MI:0915”(physical association)	0.560
GPRASP1	OPRK1	psi-mi:“MI:0407”(direct interaction)	0.440
HCRTR1	OPRK1	psi-mi:“MI:0915”(physical association)	0.400
	OPRK1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	OPRK1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	OPRK1	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	OPRK1	psi-mi:“MI:0915”(physical association)	0.400
OPRK1	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
OPRK1	SIAH1	psi-mi:“MI:0915”(physical association)	0.400
SIAH2	OPRK1	psi-mi:“MI:0915”(physical association)	0.400
OPRK1	WLS	psi-mi:“MI:0915”(physical association)	0.400
GJA4	OPRK1	psi-mi:“MI:0915”(physical association)	0.400
OPRK1	VAPA	psi-mi:“MI:0915”(physical association)	0.400
AUP1	OPRK1	psi-mi:“MI:0915”(physical association)	0.400
NHERF1	OPRK1	psi-mi:“MI:0915”(physical association)	0.400
GABARAP	OPRK1	psi-mi:“MI:0915”(physical association)	0.370
NKG7	OPRK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): AUP1 (Affinity Capture-Western), GJA4 (Affinity Capture-Western), DOK4 (Affinity Capture-Western), SIAH1 (Affinity Capture-Western), SIAH2 (Affinity Capture-Western), VAPA (Affinity Capture-Western), WLS (Affinity Capture-Western), OPRK1 (Two-hybrid), GABARAPL1 (Affinity Capture-Western), OPRK1 (Reconstituted Complex), SLC9A3R1 (Affinity Capture-Western), GABARAPL1 (Two-hybrid), GABARAPL1 (Affinity Capture-Western), NKG7 (Two-hybrid), SLC9A3R1 (Affinity Capture-Western)

ESM2 similar proteins: A5A4K9, A5A4L1, B2ZI34, F1MV99, O08725, O08786, O42329, O43193, O62709, O97772, P11616, P21451, P21729, P24053, P25099, P26684, P28088, P28190, P28646, P30542, P30550, P30551, P30872, P30873, P32238, P33534, P34970, P34975, P35342, P41144, P41145, P47745, P47751, P48302, P52500, P60893, P60894, P60895, Q2KIP6, Q49LX5

Diamond homologs: A0T2N3, A1ZAX0, E7F7V7, F1MV99, F1R332, O08726, O08858, O43603, O60755, O88626, O88853, O88854, O97666, P14600, P21109, P25024, P25025, P25103, P28646, P30547, P30548, P30680, P30731, P30872, P30873, P30874, P30875, P30937, P30938, P30974, P30975, P31391, P32300, P32303, P32745, P33396, P33533, P33534, P33535, P34975

SIGNOR signaling

50 interactions.

A	Effect	B	Mechanism
Matrine	up-regulates	OPRK1	“chemical activation”
OPRK1	“up-regulates activity”	GNAI1	binding
OPRK1	“up-regulates activity”	GNAI3	binding
OPRK1	“up-regulates activity”	GNAO1	binding
OPRK1	“up-regulates activity”	GNAZ	binding
“Dynorphin A”	“up-regulates activity”	OPRK1	“chemical activation”
MECP2	“up-regulates quantity by expression”	OPRK1	“post transcriptional regulation”
alvimopan	“down-regulates activity”	OPRK1	“chemical inhibition”
hydromorphone	“up-regulates activity”	OPRK1	“chemical activation”
methylnaltrexone	“down-regulates activity”	OPRK1	“chemical inhibition”
2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol	“up-regulates activity”	OPRK1	“chemical activation”
POMC	“up-regulates activity”	OPRK1	“chemical activation”
PDYN	“up-regulates activity”	OPRK1	binding
PDYN	“up-regulates activity”	OPRK1	“chemical activation”
Quadazocine	“down-regulates activity”	OPRK1	“chemical inhibition”
“Naloxone benzoylhydrazone”	“up-regulates activity”	OPRK1	“chemical activation”
Naltriben	“down-regulates activity”	OPRK1	“chemical inhibition”
nalbuphine	“up-regulates activity”	OPRK1	“chemical activation”
pentazocine	“up-regulates activity”	OPRK1	“chemical activation”
buprenorphine	“down-regulates activity”	OPRK1	“chemical inhibition”
naloxone	“down-regulates activity”	OPRK1	“chemical inhibition”
Diprenorphine	“down-regulates activity”	OPRK1	“chemical inhibition”
Ethylketocyclazocine	“up-regulates activity”	OPRK1	“chemical activation”
Nalorphine	“up-regulates activity”	OPRK1	“chemical activation”
Tifluadom	“up-regulates activity”	OPRK1	“chemical activation”
U50488	“up-regulates activity”	OPRK1	“chemical activation”
naltrexone	“down-regulates activity”	OPRK1	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

572 predictions. Top by Δscore:

Variant	Effect	Δscore
8:53229827:CGT:C	acceptor_gain	0.9900
8:53229842:A:T	acceptor_gain	0.9900
8:53229843:A:AC	acceptor_gain	0.9900
8:53229843:A:C	acceptor_gain	0.9900
8:53229851:C:CT	acceptor_gain	0.9900
8:53234753:TCTTA:T	donor_loss	0.9900
8:53234754:CTTAC:C	donor_loss	0.9900
8:53234755:TTAC:T	donor_loss	0.9900
8:53234756:TA:T	donor_loss	0.9900
8:53234757:A:AG	donor_loss	0.9900
8:53234762:C:A	donor_gain	0.9900
8:53250774:CGCT:C	donor_loss	0.9900
8:53250775:GCTCA:G	donor_loss	0.9900
8:53250776:CT:C	donor_loss	0.9900
8:53250777:TCA:T	donor_loss	0.9900
8:53250778:C:CG	donor_loss	0.9900
8:53250779:A:C	donor_loss	0.9900
8:53229830:C:CC	acceptor_gain	0.9800
8:53229841:CAA:C	acceptor_gain	0.9800
8:53234757:ACCTT:A	donor_gain	0.9800
8:53234758:CCTTC:C	donor_gain	0.9800
8:53234944:A:C	acceptor_gain	0.9800
8:53250779:A:AC	donor_gain	0.9800
8:53250780:C:CC	donor_gain	0.9800
8:53250780:CCGG:C	donor_gain	0.9800
8:53250833:C:CT	donor_gain	0.9800
8:53250834:T:TT	donor_gain	0.9800
8:53251086:C:CC	acceptor_gain	0.9800
8:53251442:GCTTA:G	donor_loss	0.9800
8:53251443:CTTA:C	donor_loss	0.9800

AlphaMissense

2517 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:53229460:G:T	P327H	1.000
8:53229468:G:C	S324R	1.000
8:53229468:G:T	S324R	1.000
8:53229470:T:G	S324R	1.000
8:53229471:A:C	S323R	1.000
8:53229471:A:T	S323R	1.000
8:53229473:T:G	S323R	1.000
8:53229474:G:C	N322K	1.000
8:53229474:G:T	N322K	1.000
8:53229574:G:C	P289R	1.000
8:53229574:G:T	P289H	1.000
8:53229581:A:G	W287R	1.000
8:53229581:A:T	W287R	1.000
8:53229584:A:G	C286R	1.000
8:53229591:G:C	F283L	1.000
8:53229591:G:T	F283L	1.000
8:53229593:A:G	F283L	1.000
8:53229707:A:G	C245R	1.000
8:53229727:G:C	P238R	1.000
8:53229727:G:T	P238H	1.000
8:53229811:C:G	C210S	1.000
8:53229812:A:G	C210R	1.000
8:53229812:A:T	C210S	1.000
8:53234822:A:G	W183R	1.000
8:53234822:A:T	W183R	1.000
8:53234893:G:T	A159D	1.000
8:53234902:C:G	R156P	1.000
8:53234903:G:T	R156S	1.000
8:53234910:G:C	S153R	1.000
8:53234910:G:T	S153R	1.000

dbSNP variants (sampled 300 via entrez): RS1000046568 (8:53237140 A>G), RS1000351840 (8:53232598 G>T), RS1000420090 (8:53243609 A>G), RS1000433662 (8:53249438 C>G,T), RS1000508007 (8:53225474 G>A,T), RS1000577402 (8:53226738 T>C), RS1000688101 (8:53231262 A>G), RS1000713948 (8:53226440 G>T), RS1000796229 (8:53251147 C>A,G,T), RS1000958094 (8:53232231 A>G), RS1001015619 (8:53245059 G>T), RS1001137831 (8:53249692 T>G), RS1001156193 (8:53238493 G>A,C,T), RS1001394468 (8:53244861 T>G), RS1001485911 (8:53249410 G>A)

Disease associations

OMIM: gene MIM:165196 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002124_2	IgE levels in asthmatics (D.p. specific)	1.000000e-06
GCST007537_4	Modic changes	5.000000e-06
GCST010252_2	Systolic blood pressure x quantitative lifestyle risk score interaction (2df test)	7.000000e-07
GCST010989_140	Body size at age 10	4.000000e-08
GCST90000047_157	Age at first sexual intercourse	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0010724	lifestyle measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095151 (SELECTIVITY GROUP), CHEMBL2095156 (SELECTIVITY GROUP), CHEMBL2095181 (PROTEIN FAMILY), CHEMBL237 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

344 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 657,441 (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
CHEMBL19019	NALTREXONE	4	34,647
CHEMBL1254682	LEVALLORPHAN	4	7,151
CHEMBL80	NALOXONE	4	38,742
CHEMBL1201149	NALTREXONE HYDROCHLORIDE	4	3,278
CHEMBL1718	NALOXONE HYDROCHLORIDE	4	4,865
CHEMBL607	MEPERIDINE	4	43,837
CHEMBL70	MORPHINE	4	128,573
CHEMBL963	OXYMORPHONE	4	25,955
CHEMBL100116	PENTAZOCINE	4	33,194
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1078261	PROPIVERINE	4	4,890
CHEMBL1086	DIBUCAINE	4	17,231
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL110	BENZNIDAZOLE	4	3,668
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1117	IDARUBICIN	4
CHEMBL114	SAQUINAVIR	4
CHEMBL1163	ATAZANAVIR	4
CHEMBL1170	TESTOSTERONE PROPIONATE	4
CHEMBL1172	DESLORATADINE	4
CHEMBL1175	DULOXETINE	4
CHEMBL1183717	ALMITRINE	4
CHEMBL1186579	METHYLNALTREXONE	4
CHEMBL12	DIAZEPAM	4
CHEMBL1200374	EXEMESTANE	4

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

PharmGKB clinical annotations

11 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10111937	Toxicity	3	cocaine	Cocaine dependence
rs1051660	Toxicity	3	heroin	Heroin Dependence
rs1051660	Dosage	3	morphine	Neoplasms;Pain
rs3802279	Dosage	3	methadone	Heroin Dependence
rs3802281	Dosage	3	methadone	Heroin Dependence
rs6473797	Toxicity	3	heroin	Heroin Dependence
rs6473797	Toxicity	3	ethanol	Alcohol abuse
rs702764	Efficacy	3	butorphanol
rs963549	Dosage	3	methadone	Heroin Dependence
rs997917	Toxicity	3	cocaine	Cocaine dependence
rs997917	Toxicity	3	opioids	Opioid-Related Disorders

PharmGKB variants

17 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1051660	OPRK1	3	2.50	2	heroin;morphine
rs7016778	OPRK1		0.00	0
rs963549	OPRK1	3	2.50	1	methadone
rs702764	OPRK1	3	0.00	1	butorphanol
rs6473797	OPRK1	3	2.75	2	ethanol;heroin
rs6473799	OPRK1		0.00	0
rs16918875	OPRK1		0.00	0
rs6985606	OPRK1		0.00	0
rs7813478	OPRK1		0.00	0
rs16918909	OPRK1		0.00	0
rs16918941	OPRK1		0.00	0
rs997917	OPRK1	3	0.00	2	cocaine;opioids
rs16918842	OPRK1		0.00	0
rs3802279	OPRK1	3	2.50	1	methadone
rs3802281	OPRK1	3	2.50	1	methadone
rs3808627	OPRK1		0.00	0
rs10111937	OPRK1	3	0.00	1	cocaine

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Opioid receptors

Most potent curated ligand interactions (89 total), top 25:

Ligand	Action	Affinity	Parameter
JDTic	Antagonist	11.22	pKi
nor-binaltorphimine	Antagonist	11.0	pKi
anrikefon	Agonist	10.95	pEC50
dynorphin A	Full agonist	10.8	pKi
dynorphin A-(1-13)	Full agonist	10.7	pKi
(-)-bremazocine	Partial agonist	10.5	pKi
ICI-199441	Agonist	10.4	pKi
α-neoendorphin	Full agonist	10.2	pKi
buprenorphine	Antagonist	10.2	pKi
nalfurafine	Full agonist	10.1	pKd
(-)-cyclazocine	Partial agonist	10.0	pKi
ethylketocyclazocine	Full agonist	10.0	pKi
butorphanol	Partial agonist	9.92	pKi
dynorphin A-(1-8)	Full agonist	9.9	pKi
dynorphin B	Partial agonist	9.9	pKi
5’-guanidinonaltrindole	Antagonist	9.9	pKi
difelikefalin	Agonist	9.8	pEC50
diprenorphine	Antagonist	9.7	pKi
dynorphin-(1-11)	Full agonist	9.7	pKi
β-FNA	Antagonist	9.7	pKi
quadazocine	Antagonist	9.7	pKi
GR 89696	Full agonist	9.7	pKi
[D-Ala2,F5,Phe4]dynorphin-(1-17)-NH2	Full agonist	9.7	pIC50
dynorphin-(1-17)-NH2	Full agonist	9.7	pIC50
etorphine	Full agonist	9.7	pKi

Binding affinities (BindingDB)

1910 measured of 2317 human assays (2396 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2R)-N-[(2R)-6-amino-1-oxo-1-(1-oxo-2,8-diazaspiro[4.5]decan-8-yl)hexan-2-yl]-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanamide	EC50	0.0027 nM	US-9359399: Synthetic peptide amides
(2R)-N-[(2R)-6-amino-1-[4-(3,5-dimethyl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-oxohexan-2-yl]-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanamide	EC50	0.0042 nM	US-9359399: Synthetic peptide amides
(2R)-N-[(2R)-6-amino-1-oxo-1-[4-(2-oxo-3H-indol-1-yl)piperidin-1-yl]hexan-2-yl]-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanamide	EC50	0.005 nM	US-9359399: Synthetic peptide amides
CHEMBL2338721	EC50	0.0061 nM
(2R)-6-amino-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-N-[(5-methylpyrazin-2-yl)methyl]hexanamide	EC50	0.0064 nM	US-9359399: Synthetic peptide amides
CHEMBL2338723	EC50	0.007 nM
CHEMBL2338724	EC50	0.0077 nM
(2R)-N-[(2R)-6-amino-1-(2-methyl-1-oxo-2,8-diazaspiro[4.5]decan-8-yl)-1-oxohexan-2-yl]-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanamide	EC50	0.0083 nM	US-9359399: Synthetic peptide amides
CHEMBL2338725	EC50	0.0098 nM
BW373U86	KI	0.01 nM
CAS_111555-58-9	KI	0.01 nM
CHEMBL2338720	EC50	0.013 nM
(2R)-N-[(2R)-6-amino-1-[4-(morpholine-4-carbonyl)piperidin-1-yl]-1-oxohexan-2-yl]-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanamide	EC50	0.0145 nM	US-9359399: Synthetic peptide amides
(2R)-N-[(2R)-6-amino-1-oxo-1-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)hexan-2-yl]-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanamide	EC50	0.0165 nM	US-9359399: Synthetic peptide amides
CHEMBL2338722	EC50	0.02 nM
(2R)-6-amino-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-N-(imidazo[1,2-a]pyridin-2-ylmethyl)hexanamide	EC50	0.0208 nM	US-9359399: Synthetic peptide amides
CHEMBL4082823	EC50	0.0222 nM
CHEMBL4103819	EC50	0.025 nM
CHEMBL4064781	EC50	0.0257 nM
(1R,9R,10S)-N-benzyl-17-(cyclopropylmethyl)-4-methoxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-amine	KI	0.026 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
CHEMBL4080324	EC50	0.0288 nM
CHEMBL2338726	EC50	0.029 nM
(1S,9R,10S,12S)-16-(cyclopropylmethyl)-N-[(3,4-dichlorophenyl)methyl]-4,10-dihydroxy-16-azatetracyclo[7.4.3.01,10.02,7]hexadeca-2(7),3,5-triene-12-carboxamide	EC50	0.03 nM	US-9656962: Ring-contracted morphinans and the use thereof
N-[(1R,9R,10S)-17-(cyclopropylmethyl)-4-methoxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-yl]benzamide	KI	0.032 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
CHEMBL2338719	EC50	0.035 nM
(1S,2S,6R,14R,16R)-5-(cyclopropylmethyl)-16-(furan-3-ylmethoxymethyl)-15-methoxy-16-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol	EC50	0.037 nM	US-9988392: 7-beta-alkyl analogs of orvinols
(1S,2S,6R,14R,16R)-5-(cyclopropylmethyl)-15-methoxy-16-methyl-16-(phenylmethoxymethyl)-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol	EC50	0.047 nM	US-9988392: 7-beta-alkyl analogs of orvinols
20-cyclopropylmethyl-(1R,12R)-7-thia-5,20-diazapentacyclo[10.5.3.01,13.02,10.04,8]icosa-2(10),3,5,8-tetraen-6-amine	KI	0.049 nM
CHEMBL4090628	EC50	0.0494 nM
Isopentyl Orvinol M320	EC50	0.051 nM
(1R,9R,10S)-N-(cyclohexylmethyl)-17-(cyclopropylmethyl)-4-methoxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-amine	KI	0.052 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
CHEMBL2338718	EC50	0.052 nM
4-chloro-N-[(1R,9R,10S)-17-(cyclopropylmethyl)-4-methoxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-yl]benzenesulfonamide	KI	0.057 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
N-[(1R,9R,10S)-17-(cyclopropylmethyl)-4-hydroxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-yl]-2,2-dimethylpropanamide	KI	0.059 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
CHEMBL2338738	KI	0.059 nM
(2S)-2-amino-N-[[(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11-hydroxy-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-16-yl]methyl]-4-methylpentanamide	KI	0.06 nM	US-8969358: Buprenorphine analogs
N-[(1R,9R,10S)-17-(cyclopropylmethyl)-4-hydroxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-13-yl]benzamide	KI	0.062 nM	US-9862726: Opioid receptor modulating oxabicyclo[2.2.2]octane morphinans
N-[[(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11-hydroxy-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-16-yl]methyl]pyrrolidine-2-carboxamide	KI	0.07 nM	US-8969358: Buprenorphine analogs
N-[[(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11-hydroxy-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-16-yl]methyl]-4-methylbenzenesulfonamide	KI	0.07 nM	US-8969358: Buprenorphine analogs
5’-Guanidinonaltrindole (5’-GNTI)	IC50	0.07 nM
(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11,15-dimethoxy-16-[(2-methylphenyl)methoxymethyl]-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	KI	0.07 nM	US-8530494: Buprenophine analogs
CHEMBL2338717	EC50	0.077 nM
CHEMBL4069608	EC50	0.0799 nM
N-[[(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11-hydroxy-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-16-yl]methyl]benzenesulfonamide	KI	0.08 nM	US-8969358: Buprenorphine analogs
1-[[(1S,2S,6R,14R,16R)-5-(cyclopropylmethyl)-11-hydroxy-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-16-yl]methyl]-3-phenylurea	KI	0.08 nM	US-8969358: Buprenorphine analogs
(1S,2S,6R,14R,15R,16R)-11,15-dimethoxy-5-methyl-16-(naphthalen-1-ylmethoxymethyl)-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	KI	0.08 nM	US-8530494: Buprenophine analogs
CHEMBL3291216	KI	0.08 nM
(1S,2S,6R,14R,16R)-5-(cyclopropylmethyl)-11,15-dimethoxy-16-methyl-16-(phenylmethoxymethyl)-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	EC50	0.085 nM	US-9988392: 7-beta-alkyl analogs of orvinols
(2S)-2-amino-1-[(1S,9R,10S)-17-(cyclopropylmethyl)-4-hydroxy-12,17-diazatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-12-yl]propan-1-one	KI	0.09 nM	US-8937084: Nitrogen containing morphinan derivatives and the use thereof
(2S,3S)-2-amino-N-[[(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11-hydroxy-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-16-yl]methyl]-3-methylpentanamide	KI	0.09 nM	US-8969358: Buprenorphine analogs

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	JDTIC
10.96	EC50	0.011	nM	CHEMBL2338747
10.94	EC50	0.0116	nM	CHEMBL4111684
10.89	EC50	0.013	nM	CHEMBL2338720
10.85	Ki	0.014	nM	CHEMBL4109154
10.84	EC50	0.0145	nM	CHEMBL4110548
10.82	Ki	0.015	nM	CHEMBL2338742
10.82	EC50	0.015	nM	SALVINORIN A
10.82	EC50	0.015	nM	CHEMBL5178795
10.82	Ki	0.015	nM	CHEMBL593214
10.81	EC50	0.0155	nM	CHEMBL4760663
10.80	EC50	0.016	nM	CHEMBL2338753
10.80	Ki	0.016	nM	CHEMBL4859512
10.78	EC50	0.0165	nM	CHEMBL4115291
10.77	EC50	0.017	nM	CHEMBL2338750
10.77	Ki	0.017	nM	CHEMBL4071862
10.74	IC50	0.018	nM	CHEMBL603370
10.72	Ki	0.019	nM	CHEMBL2338716
10.72	EC50	0.019	nM	CHEMBL3359804
10.72	Ki	0.019	nM	NALFURAFINE
10.70	EC50	0.02	nM	CHEMBL2338722
10.70	Ki	0.02	nM	CHEMBL2338717
10.70	Ki	0.02	nM	DIPRENORPHINE
10.70	Ki	0.02	nM	CHEMBL4108017
10.70	Ki	0.02	nM	CHEMBL110124
10.70	IC50	0.02	nM	CHEMBL277863
10.68	EC50	0.0208	nM	CHEMBL4107432
10.65	EC50	0.0222	nM	CHEMBL4082823
10.60	Ki	0.025	nM	CHEMBL2338718
10.60	EC50	0.025	nM	CHEMBL4103819
10.60	EC50	0.025	nM	NALFURAFINE
10.59	EC50	0.0257	nM	CHEMBL4064781
10.59	Ki	0.026	nM	CHEMBL6067837
10.57	EC50	0.027	nM	CHEMBL2338748
10.57	Ki	0.027	nM	NORBINALTORPHIMINE
10.57	Ki	0.0272	nM	CHEMBL5185211
10.57	EC50	0.027	nM	CHEMBL5970002
10.57	Kd	0.027	nM	CHEMBL1795714
10.55	EC50	0.0283	nM	CHEMBL4077552
10.55	EC50	0.028	nM	CHEMBL4066058
10.55	Kd	0.028	nM	CHEMBL5421947
10.54	EC50	0.029	nM	CHEMBL2338726
10.54	EC50	0.0288	nM	CHEMBL4080324
10.54	EC50	0.029	nM	CHEMBL2028997
10.54	Kd	0.029	nM	CHEMBL2311186
10.52	EC50	0.03	nM	SALVINORIN A
10.52	Ki	0.03	nM	JDTIC
10.52	EC50	0.03	nM	CHEMBL6020781
10.52	Ki	0.03	nM	CHEMBL571767
10.52	Ki	0.03	nM	CHEMBL107420

PubChem BioAssay actives

3023 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
methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-9-acetyloxy-2-(2-ethynylfuran-3-yl)-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate	1171840: Agonist activity at human KOR expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation after 30 mins by luminescence assay	ec50	<0.0001	uM
(E)-N-[(4R,4aS,7R,7aR,12bS,13S)-3-(cyclopropylmethyl)-4a,9,13-trihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-(furan-3-yl)-N-methylprop-2-enamide	1487648: Agonist activity at human kappa opioid receptor	ec50	<0.0001	uM
methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-9-acetyloxy-2-(2-bromofuran-3-yl)-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate	1171840: Agonist activity at human KOR expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation after 30 mins by luminescence assay	ec50	<0.0001	uM
(1S,15R)-N-benzyl-5-(cyclopropylmethyl)-11,15-dihydroxy-13-oxa-5,17-diazahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,16-tetraene-16-carboxamide	1167689: Agonist activity at human kappa opioid receptor expressed in CHO cells by [35S]GTPgammaS binding assay	ec50	<0.0001	uM
(1R,2S,6R,14R,15R,19R)-5-(cyclopropylmethyl)-19-[(R)-hydroxy-(3-methylphenyl)methyl]-15-methoxy-19-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11,16-tetraen-11-ol	1228369: Displacement of [3H]diprenorphine from human kappa opioid receptor expressed in CHO cell membranes incubated for 1 hr by beta counting method	ki	<0.0001	uM
1-ethyl-10-[(1-hydroxycyclopropyl)methyl]-13,13-dimethyl-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-ol	488649: Binding affinity to kappa opioid receptor	ki	<0.0001	uM
(1R,12S,13R)-20-(cyclopropylmethyl)-7-thia-5,20-diazapentacyclo[10.5.3.01,13.02,10.04,8]icosa-2,4(8),5,9-tetraen-6-amine	1274762: Displacement of [3H]U69,593 from human kappa opioid receptor expressed in CHO cell membrane	ki	<0.0001	uM
methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-9-acetyloxy-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate	1171840: Agonist activity at human KOR expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation after 30 mins by luminescence assay	ec50	<0.0001	uM
N-[(4R,4aR,7R,7aR,12bS)-3-(cyclopropylmethyl)-9-hydroxy-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-iodobenzamide	2007418: Binding affinity to wild type human KOR assessed as inhibition constant	ki	<0.0001	uM
4-amino-1-[(2R)-6-amino-2-[[(2R)-4-methyl-2-[[(2R)-3-phenyl-2-[[2-[[(2R)-2-phenylpropyl]amino]acetyl]amino]propanoyl]amino]pentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid	1725716: Agonist activity at human kappa opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 5 hrs by One-Glo luciferase assay	ec50	<0.0001	uM
4-amino-1-[(2R)-6-amino-2-[[(2R)-4-methyl-2-[[(2R)-3-phenyl-2-[[2-[[(2S)-2-phenylpropyl]amino]acetyl]amino]propanoyl]amino]pentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid	1725716: Agonist activity at human kappa opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 5 hrs by One-Glo luciferase assay	ec50	<0.0001	uM
4-amino-1-[(2R)-6-amino-2-[[(2R)-4-methyl-2-[[(2R)-2-[[2-[[(2R)-3-methyl-2-phenylbutyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]pentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid	1725716: Agonist activity at human kappa opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 5 hrs by One-Glo luciferase assay	ec50	<0.0001	uM
4-amino-1-[(2R)-6-amino-2-[[(2R)-4-methyl-2-[[(2R)-3-phenyl-2-[[2-(2-phenylbutylamino)acetyl]amino]propanoyl]amino]pentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid	1725716: Agonist activity at human kappa opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 5 hrs by One-Glo luciferase assay	ec50	<0.0001	uM
(2R)-N-[(2R)-6-amino-1-[4-(methylcarbamoylamino)piperidin-1-yl]-1-oxohexan-2-yl]-4-methyl-2-[[(2R)-3-phenyl-2-[[2-[[(2R)-2-phenylpropyl]amino]acetyl]amino]propanoyl]amino]pentanamide	1725716: Agonist activity at human kappa opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 5 hrs by One-Glo luciferase assay	ec50	<0.0001	uM
tetralithium;[[(2R,3S,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl] dioxidophosphinothioyl phosphate	450031: Antagonist activity at kappa opioid receptor expressed in HEK293 cells assessed as inhibition of compound 16-induced [35S]GTPgammaS binding	ki	<0.0001	uM
(E)-N-[(4R,4aS,7R,7aR,12bS,13S)-3-(cyclopropylmethyl)-4a,9,13-trihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-N-methyl-3-thiophen-3-ylprop-2-enamide	1487650: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation by TR-FRET assay	ec50	<0.0001	uM
(E)-N-[(4R,4aS,7R,7aR,12bS,13S)-3-(cyclopropylmethyl)-4a,9,13-trihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-N-methyl-3-pyridin-4-ylprop-2-enamide	1487650: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation by TR-FRET assay	ec50	<0.0001	uM
3-[2-[cyclopentylmethyl(2-phenylethyl)amino]ethyl]phenol;hydrochloride	1451322: Displacement of [3H]U69,593 from human kappa opioid receptor expressed in CHO cell membranes after 60 mins by liquid scintillation counting method	ki	<0.0001	uM
(E)-N-[(4R,4aS,7R,7aR,12bS,13S)-3-(cyclopropylmethyl)-4a,9,13-trihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-N-methyl-3-(4-methylphenyl)prop-2-enamide	1487650: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation by TR-FRET assay	ec50	<0.0001	uM
(E)-N-[(4R,4aS,7R,7aR,12bS,13S)-3-(cyclopropylmethyl)-4a,9,13-trihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-N-methyl-3-thiophen-2-ylprop-2-enamide	1487650: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation by TR-FRET assay	ec50	<0.0001	uM
(E)-N-[(4R,4aS,7R,7aR,12bS,13S)-3-(cyclopropylmethyl)-4a,9,13-trihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-N-methyl-3-phenylprop-2-enamide	1487650: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation by TR-FRET assay	ec50	<0.0001	uM
(E)-N-[(4R,4aS,7R,7aR,12bS,13S)-3-(cyclopropylmethyl)-4a,9,13-trihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-(4-chlorophenyl)-N-methylprop-2-enamide	1487650: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation by TR-FRET assay	ec50	<0.0001	uM
(E)-N-[(4R,4aS,7R,7aR,12bS,13S)-3-(cyclopropylmethyl)-4a,9,13-trihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-N-methyl-3-pyridin-2-ylprop-2-enamide	1487650: Agonist activity at human kappa opioid receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation by TR-FRET assay	ec50	<0.0001	uM
3-[2-[cyclohexylmethyl(2-phenylethyl)amino]ethyl]-2-fluorophenol;hydrochloride	1451322: Displacement of [3H]U69,593 from human kappa opioid receptor expressed in CHO cell membranes after 60 mins by liquid scintillation counting method	ki	<0.0001	uM
methyl 4-[2-(3,4-dichlorophenyl)acetyl]-3-(3,6-dihydro-2H-pyridin-1-ylmethyl)piperazine-1-carboxylate	148434: In vitro agonist activity at kappa opioid receptor in rabbit vas deferens.	ic50	<0.0001	uM
N-[(4R,4aS,7aR,12bR)-3-(cyclopropylmethyl)-9-hydroxy-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-yl]-3-(4-chlorophenyl)propanamide	273145: Activity at human recombinant kappa opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding	ic50	<0.0001	uM
(4R,4aS,7aR,12bR)-4a-[3-(4-chlorophenyl)propylamino]-3-(cyclopropylmethyl)-9-hydroxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one	273145: Activity at human recombinant kappa opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S binding	ic50	<0.0001	uM
(2R)-N-[(2R)-6-amino-1-morpholin-4-yl-1-oxohexan-2-yl]-4-methyl-2-[[(2R)-3-phenyl-2-[[2-(3-phenylpropylamino)acetyl]amino]propanoyl]amino]pentanamide	1725716: Agonist activity at human kappa opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 5 hrs by One-Glo luciferase assay	ec50	<0.0001	uM
(2R)-N-[(2R)-6-amino-1-morpholin-4-yl-1-oxohexan-2-yl]-4-methyl-2-[[(2R)-3-phenyl-2-[[2-(2-phenylethylamino)acetyl]amino]propanoyl]amino]pentanamide	1725716: Agonist activity at human kappa opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 5 hrs by One-Glo luciferase assay	ec50	<0.0001	uM
(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-15-methoxy-16-[3-[(4-methoxyphenyl)methylamino]phenyl]-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol	1781407: Displacement of [3H]U69,593 from human kappa opioid receptor expressed in CHO cell membrane measured after 30 mins by liquid scintillation counting method	ki	<0.0001	uM
(R)-[(1S,2S,6R,14R,15R,16S)-5-(cyclopropylmethyl)-11,15-dimethoxy-16-methyl-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-16-yl]-phenylmethanol	1885860: Agonist activity at human KOR expressed in CHO cell membranes after 1 hr by [35S]GTPgammaS binding assay	ec50	<0.0001	uM
(E)-N-[(4R,7R,7aR,12bS)-3-(cyclopropylmethyl)-9-hydroxy-2,4,4a,5,6,7,7a,13-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-(furan-3-yl)-N-methylprop-2-enamide	1877879: Displacement of [3H]DPDPE from human KOR expressed in HEK293 cell membrane	ki	<0.0001	uM
(E)-N-[(4R,7R,7aR,12bS)-3-(cyclopropylmethyl)-9-hydroxy-2,4,6,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-(furan-3-yl)-N-methylprop-2-enamide	1877879: Displacement of [3H]DPDPE from human KOR expressed in HEK293 cell membrane	ki	<0.0001	uM
5-chloro-3-[1-(pyrrolidin-1-ylmethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2,3-dihydroinden-1-one	1303901: Displacement of [3H]diprenorphine from human kappa opioid receptor expressed in CHO cell membranes after 30 mins by liquid scintillation counting analysis	ki	<0.0001	uM
Difelikefalin	1725716: Agonist activity at human kappa opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 5 hrs by One-Glo luciferase assay	ec50	<0.0001	uM
(E)-N-[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-phenylprop-2-enamide	395280: Displacement of [3H]diprenorphine from human kappa opioid receptor expressed in CHO cell membrane by liquid scintillation and luminescence counter	ki	<0.0001	uM
2-[6-(dimethylsulfamoyl)-1,3-benzodioxol-5-yl]-N-methyl-N-[(1S)-1-phenyl-2-pyrrolidin-1-ylethyl]acetamide	331201: Agonist activity at human kappa opioid receptor transfected in CHO cells by [35S]GTP-gamma-S binding assay	ec50	0.0001	uM
(1S,9R,13R)-10-(cyclopropylmethyl)-1,13-dimethyl-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-ol	310354: Displacement of [3H]U-69593 from kappa opioid receptor expressed in CHO cells	ki	0.0001	uM
2-[6-[benzyl(methyl)sulfamoyl]-1,3-benzodioxol-5-yl]-N-methyl-N-[(1S)-1-phenyl-2-pyrrolidin-1-ylethyl]acetamide	331201: Agonist activity at human kappa opioid receptor transfected in CHO cells by [35S]GTP-gamma-S binding assay	ec50	0.0001	uM
bis[(1R,9R,10R)-17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl] butanedioate	148149: Inhibitory activity against Opioid receptor kappa 1 in chinese Hamster Ovary (CHO) cell membranes was determined using [3H]U-69593 radioligand	ki	0.0001	uM
(1S,13R)-10-(cyclopropylmethyl)-1,13-dimethyl-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-triene-4-carboxamide	270234: Displacement of [3H]U-69593 from human kappa opioid receptor expressed in CHO cells	ki	0.0001	uM
N-methyl-N-[(1S)-1-phenyl-2-pyrrolidin-1-ylethyl]-2-[3-(trifluoromethyl)phenyl]acetamide	148022: In vitro binding affinity towards Opioid receptor kappa 1 by displacement of bound [3H]U-69593	ki	0.0001	uM
N-methyl-2-(3-nitrophenyl)-N-[(1S)-1-phenyl-2-pyrrolidin-1-ylethyl]acetamide	148022: In vitro binding affinity towards Opioid receptor kappa 1 by displacement of bound [3H]U-69593	ki	0.0001	uM
N-methyl-N-[(1S)-1-phenyl-2-pyrrolidin-1-ylethyl]-2-[2-(trifluoromethyl)phenyl]acetamide	148022: In vitro binding affinity towards Opioid receptor kappa 1 by displacement of bound [3H]U-69593	ki	0.0001	uM
bis[(1R,9R,10R)-17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl] (E)-but-2-enedioate	1274752: Displacement of [3H]U69593 from human kappa opioid receptor expressed in CHO cell membrane	ki	0.0001	uM
(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]-N-[(2S)-1,6-diamino-1-oxohexan-2-yl]pyrrolidine-2-carboxamide	148006: In vitro binding affinity towards human Opioid receptor kappa 1 on CHO cell membranes using [3H]diprenorphine displacement.	ki	0.0001	uM
bis[(1R,9R,10R)-17-(cyclopropylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl] butanedioate	148149: Inhibitory activity against Opioid receptor kappa 1 in chinese Hamster Ovary (CHO) cell membranes was determined using [3H]U-69593 radioligand	ki	0.0001	uM
2-anilino-N-[(1S)-2-[(3S)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-N-methylacetamide	260175: Agonist activity at kappa opioid receptor in a [35S]GTP-gamma-S functional assay	ec50	0.0001	uM
2-(3,4-dichloroanilino)-N-[(1S)-2-[(3S)-3-hydroxypyrrolidin-1-yl]-1-phenylethyl]-N-methylacetamide	260174: Binding affinity to kappa opioid receptor	ki	0.0001	uM
10-O-[(1R,9R,10R)-17-(cyclobutylmethyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-4-yl] 1-O-methyl decanedioate	148149: Inhibitory activity against Opioid receptor kappa 1 in chinese Hamster Ovary (CHO) cell membranes was determined using [3H]U-69593 radioligand	ki	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
trichostatin A	affects cotreatment, decreases expression, increases expression	3
U 69593	affects binding, decreases reaction, increases activity	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer	increases activity, decreases reaction, affects binding	2
GUM1 compound	increases activity	1
mitragynine	affects binding, decreases reaction, increases activity	1
methylmercuric chloride	decreases expression	1
nalmefene	affects binding, decreases activity	1
celastrol	decreases expression	1
ICI 199441	affects binding, increases activity	1
cyclorphan	affects binding	1
CGP 52608	affects binding, increases reaction	1
gedunin	decreases expression	1
entinostat	decreases expression	1
bardoxolone methyl	decreases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
7-hydroxymitragynine	affects binding, decreases reaction, increases activity	1
dorsomorphin	increases expression, affects cotreatment, decreases expression	1
bisphenol S	decreases methylation	1
3-chloro-4-(4-((2-(3-pyridyl)pyrrolidin-1-yl)methyl)phenoxy)benzamide	affects binding	1
3-fluoro-4-(4-((2-(3-fluorophenyl)pyrrolidin-1-yl)methyl)phenoxy)benzamide	affects binding, decreases activity	1
Resveratrol	affects cotreatment, decreases expression	1
Fomepizole	decreases expression, decreases reaction	1
Ethanol	decreases expression, decreases reaction	1
Buprenorphine	affects binding, decreases reaction	1
Cadmium	increases abundance, decreases expression	1

ChEMBL screening assays

2263 unique, capped per target: 1416 binding, 828 functional, 14 admet, 4 toxicity, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1656363	Functional	Agonist activity at kappa/delta opioid receptor expressed in HEK293 cells coexpressing chimeric Giiq protein assessed as stimulation of intracellular calcium	A κ Opioid Pharmacophore Becomes a Spinally Selective κ-δ Agonist When Modified with a Basic Extender Arm. — ACS Med Chem Lett
CHEMBL3371072	Binding	Agonist activity at human kappa-delta opioid receptor expressed in HEK293 cells assessed as induction of beta-arrestin 2 recruitment incubated for 60 mins by fluorescent microscopy	Putative kappa opioid heteromers as targets for developing analgesics free of adverse effects. — J Med Chem
CHEMBL1737954	Unclassified	PUBCHEM_BIOASSAY: Late-stage radioligand binding dose response assay to identify inhibitors of NADPH oxidase 1 (NOX1): PDSP screen Ki Set 2. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1792, AID1796, AID182	PubChem BioAssay data set

Cellosaurus cell lines

7 cell lines: 3 spontaneously immortalized cell line, 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0TB	ACTOne OPRK1	Transformed cell line	Female
CVCL_H484	CHO-K1/OPRK1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV60	cAMP Hunter CHO-K1 OPRK1 Gi	Spontaneously immortalized cell line	Female
CVCL_LA97	PathHunter U2OS OPRK1 beta-arrestin	Cancer cell line	Female
CVCL_LA98	PathHunter U2OS OPRK1 Total GPCR Internalization	Cancer cell line	Female
CVCL_ZK83	GeneBLAzer OPRK1-Gqo5-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_ZK97	Tango OPRK1-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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