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OPRD1

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Summary

OPRD1 (opioid receptor delta 1, HGNC:8153) is a protein-coding gene on chromosome 1p35.3, encoding Delta-type opioid receptor (P41143). G-protein coupled receptor that functions as a receptor for endogenous enkephalins and for a subset of other opioids.

Enables G protein-coupled enkephalin receptor activity. Involved in several processes, including G protein-coupled opioid receptor signaling pathway; cellular response to hypoxia; and positive regulation of peptidyl-serine phosphorylation. Located in plasma membrane. Implicated in alcohol dependence; alcohol use disorder; drug dependence (multiple); opioid abuse; and withdrawal disorder. Biomarker of opioid abuse.

Source: NCBI Gene 4985 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 42 total
  • Druggable target: yes — 150 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_000911

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:8153
Approved symbolOPRD1
Nameopioid receptor delta 1
Location1p35.3
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000116329
Ensembl biotypeprotein_coding
OMIM165195
Entrez4985

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000234961

RefSeq mRNA: 1 — MANE Select: NM_000911 NM_000911

CCDS: CCDS329

Canonical transcript exons

ENST00000234961 — 3 exons

ExonStartEnd
ENSE000007620022885895428859303
ENSE000008169362886274228871267
ENSE000038418592881217028812610

Expression profiles

Bgee: expression breadth broad, 63 present calls, max score 82.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7208 / max 41.0718, expressed in 171 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
18420.5560141
2014360.108963
18410.055934

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
endothelial cellCL:000011582.47silver quality
metanephric glomerulusUBERON:000473670.60gold quality
islet of LangerhansUBERON:000000669.48gold quality
primary visual cortexUBERON:000243668.51gold quality
prefrontal cortexUBERON:000045167.16gold quality
occipital lobeUBERON:000202166.21gold quality
frontal cortexUBERON:000187065.83gold quality
right frontal lobeUBERON:000281065.69gold quality
middle temporal gyrusUBERON:000277165.52silver quality
superior frontal gyrusUBERON:000266165.16gold quality
Brodmann (1909) area 23UBERON:001355465.11gold quality
dorsolateral prefrontal cortexUBERON:000983464.62gold quality
neocortexUBERON:000195064.58gold quality
Brodmann (1909) area 9UBERON:001354064.44gold quality
postcentral gyrusUBERON:000258164.12silver quality
parietal lobeUBERON:000187263.28silver quality
cerebral cortexUBERON:000095662.83gold quality
anterior cingulate cortexUBERON:000983562.23gold quality
parotid glandUBERON:000183161.24gold quality
nasal cavity epitheliumUBERON:000538461.18gold quality
telencephalonUBERON:000189360.83gold quality
putamenUBERON:000187460.45gold quality
cerebellar vermisUBERON:000472060.05gold quality
pericardiumUBERON:000240758.37gold quality
caudate nucleusUBERON:000187358.04gold quality
forebrainUBERON:000189057.98gold quality
temporal lobeUBERON:000187157.35gold quality
Ammon’s hornUBERON:000195456.73gold quality
Brodmann (1909) area 46UBERON:000648356.48gold quality
nucleus accumbensUBERON:000188256.28gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

ExperimentMarker?Max mean expression
E-MTAB-5061yes10.90
E-ANND-3yes5.55
E-ENAD-27yes4.12
E-MTAB-6075no43.76
E-GEOD-81608no4.88
E-GEOD-83139no3.52

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

TargetRegulation
SNCARepression

Upstream regulators (CollecTRI, top): ETS1, IKZF1, MBD2, RELA, SP1, SP3, TCF3, TFAP2A, USF1

miRNA regulators (miRDB)

1 targeting OPRD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-425499.1165.151315

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)
  • Gene may be linked to etiology of anorexia nervosa. (PMID:12740597)
  • random mutagenesis identified 30 activating point mutations. 3-D modeling revealed an activation path originating from the third extracellular loop and propagating through tightly packed helices III, VI and VII down to a VI-VII cytoplasmic switch. (PMID:12847517)
  • protein conformation and binding site for deltorphin ii (PMID:14999000)
  • interaction studies between the delta-opioid receptor, ligands, and G-proteins (PMID:15317820)
  • 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)
  • Results suggest that the OPRD1 gene variants may not be a factor in vulnerability to methamphetamine dependence/psychosis. (PMID:16741914)
  • Changes in the inhibitory effects of opioid receptor agonists on intracellular cAMP were used as a marker of the function delta opioid receptors (delta receptor). (PMID:16808998)
  • pharmacological chaperones facilitate plasma membrane targeting of delta-opioid receptors by binding and stabilizing receptor precursors, thereby promoting their release from the stringent ER quality control (PMID:17550902)
  • delta-opioid receptor phosphorylation regulates its beta-arrestins selectivity and subsequent receptor internalization and adenylyl cyclase desensitization (PMID:17565992)
  • The sarco(endo)plasmic reticulum Ca(2+) ATPase 2b (SERCA2b), which maintains high Ca(2+) concentration in the lumen of the endoplasmic reticulum, interacts specifically with the human delta opioid receptor. (PMID:17588601)
  • There is a positive haplotypic association between OPRd1 variants and substance dependence in European Americans. (PMID:17622222)
  • Increased delta opioid signalling is due to enhanced DOR coupling to its tethered Galpha subunit. (PMID:18182056)
  • With CXCR4 receptor, forms heterodimeric complexes that are dynamically regulated by the ligands. (PMID:18200497)
  • genes encoding the mu-, delta-, and kappa-opioid receptors may contribute to variation in personality traits (PMID:18213616)
  • Data show that CXCR2 chemokine receptor antagonism enhances delta opioid receptor (DOP) function via allosteric regulation of the CXCR2-DOP receptor heterodimer. (PMID:18307412)
  • DOP-R desensitization upon etorphine exposure relies on the GRK2, PKC and tyrosine kinases while DPDPE and deltorphin I mediate desensitization at least via tyrosine kinases. (PMID:18395423)
  • This study have used immunohistochemistry and quantified the results to demonstrate that the levels of delta- and mu-OR subtypes were high in the VZ and SVZ between 11 and 16 gestation weeks (GW) and decreased by 20GW. (PMID:18455254)
  • response to nalmefene did not vary with genotype (PMID:18537939)
  • N-glycosylation of the delta-opioid receptor is needed to maintain the expression of fully functional and stable receptor molecules at the cell surface (PMID:18703511)
  • Report human hepatic met-enkephalin and delta opioid receptor-1 immunoreactivities in viral and autoimmune hepatitis. (PMID:18753988)
  • Phe27Cys polymorphism of the hdeltaOR causes a gain-of-function phenotype, which may have implications for the regulation of receptor expression at the cell surface and possibly also for the susceptibility to pathophysiological states (PMID:19000170)
  • 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)
  • Linkage peaks were typically found in regions previously identified in linkage studies and/or containing proposed candidate genes for alcoholism including AGT, OPRD1, and PDYN. (PMID:19183129)
  • results suggest a role for G protein in delta-opioid receptor internalization, but show that alternative G protein independent pathways exist (PMID:19344370)
  • role for endogenous RGS4 protein in modulating delta-opioid receptor signaling in SH-SY5Y cells (PMID:19416973)
  • mu-opioid receptors are more dependent on cholesterol for efficient signaling than delta receptors and can be partly explained by localization of mu- but not delta-opioid receptors in cholesterol- and caveolin-enriched membrane domains (PMID:19520863)
  • Intrinsic cardiac adrenergic cells constitute a delta-opioid-regulated adrenopeptidergic paracrine system conferring robust cardioprotection through beta(2)-AR/CGRP-R co-signalling. (PMID:19581316)
  • A molecular mechanism for the formation of a DOR/secretase complex that regulates the specificity of secretase for Amyloid beta production. (PMID:20066010)
  • Results suggest that the minor G-allele of SNP rs569356 may enhance transcription factor binding and increase OPRD1 expression. (PMID:20300121)
  • human delta opioid receptor (hdeltaOR) exists in a ternary complex with SERCA2b and the ER molecular chaperone calnexin (PMID:20528919)
  • study confirmed that common single-nucleotide polymorphisms (SNPs) within OPRD1 confer risk for AN. (PMID:21079607)
  • suggest that aging individuals with at least one human delta opioid receptor(hdeltaOR)(Cys27) encoding allele might have lowered threshold for Ca(2)+ dysregulation in neurons expressing hdeltaOR (PMID:21234650)
  • Data suggest that muOR exists primarily as a dimer that will oligomerize with deltaOR into tetramers, and morphine promotes the dissociation of these tetramers. (PMID:21361347)
  • data suggest that an increased constitutive internalization and/or concurrent signaling of the delta-opioid receptor-Cys27 variant affects APP processing through altered endocytic trafficking of APP (PMID:21464208)
  • no differences in DOR mRNA levels were seen in schizophrenia. (PMID:21810780)
  • ssarrestin1 is exclusively involved in human delta-opioid receptor desensitization (PMID:22101011)
  • Cys-27 variant of human delta-opioid receptor modulates maturation and cell surface delivery of Phe-27 variant via heteromerization. (PMID:22184124)
  • between CBR and delta opioid receptor (PMID:22235275)

Cross-species orthologs

6 orthologs

OrganismSymbolGene ID
danio_reriooprd1bENSDARG00000037159
danio_reriooprd1aENSDARG00000041660
mus_musculusOprd1ENSMUSG00000050511
rattus_norvegicusOprd1ENSRNOG00000010531
drosophila_melanogasterRh7FBGN0036260
caenorhabditis_eleganstrhr-1WBGENE00016265

Paralogs (17): OPRK1 (ENSG00000082556), OPRM1 (ENSG00000112038), KISS1R (ENSG00000116014), 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

Delta-type opioid receptor — P41143 (reviewed: P41143)

All UniProt accessions (1): P41143

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor that functions as a receptor for endogenous enkephalins and for a subset of other opioids. 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 and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.

Subunit / interactions. May form homooligomers. Forms a heterodimer with OPRM1. Interacts with GPRASP1. Interacts with RTP4; the interaction promotes cell surface localization of the OPRD1-OPRM1 heterodimer.

Subcellular location. Cell membrane.

Tissue specificity. Detected in oocytes (at protein level). Detected in brain cortex, hypothalamus, hippocampus and olfactory bulb. Detected in oocytes.

Post-translational modifications. N-glycosylated. Ubiquitinated. A basal ubiquitination does not seem to be related to degradation. Ubiquitination is increased upon formation of OPRM1:OPRD1 oligomers leading to proteasomal degradation; the ubiquitination is diminished by RTP4.

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

RefSeq proteins (1): NP_000902* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000276GPCR_RhodpsnFamily
IPR000321Delta_opi_rcptFamily
IPR001418Opioid_rcptFamily
IPR017452GPCR_Rhodpsn_7TMDomain

Pfam: PF00001

UniProt features (40 total): helix 12, topological domain 8, transmembrane region 7, strand 4, glycosylation site 2, chain 1, region of interest 1, compositionally biased region 1, lipid moiety-binding region 1, disulfide bond 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

16 structures.

PDBMethodResolution (Å)
4N6HX-RAY DIFFRACTION1.8
9YDPELECTRON MICROSCOPY1.95
9CGKELECTRON MICROSCOPY2.62
4RWDX-RAY DIFFRACTION2.7
6PT2X-RAY DIFFRACTION2.8
9CGJELECTRON MICROSCOPY2.8
8Y71ELECTRON MICROSCOPY2.97
8F7SELECTRON MICROSCOPY3
9PPXELECTRON MICROSCOPY3.04
9PPYELECTRON MICROSCOPY3.1
9PQ0ELECTRON MICROSCOPY3.12
9PPZELECTRON MICROSCOPY3.19
4RWAX-RAY DIFFRACTION3.28
6PT3X-RAY DIFFRACTION3.3
9PPWELECTRON MICROSCOPY3.32
8Y45ELECTRON MICROSCOPY3.45

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P41143-F181.070.50

Antibody-complex structures (SAbDab): 1 — 9YDP

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): 333

Disulfide bonds (1): 121–198

Glycosylation sites (2): 18, 33

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

IDPathway
R-HSA-375276Peptide ligand-binding receptors
R-HSA-418594G alpha (i) signalling events
R-HSA-6785807Interleukin-4 and Interleukin-13 signaling

MSigDB gene sets: 164 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_RESPONSE_TO_ETHANOL, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_ADULT_BEHAVIOR, GOBP_ADULT_LOCOMOTORY_BEHAVIOR, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, DAWSON_METHYLATED_IN_LYMPHOMA_TCL1

GO Biological Process (19): immune response (GO:0006955), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), 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), adult locomotory behavior (GO:0008344), negative regulation of gene expression (GO:0010629), negative regulation of protein-containing complex assembly (GO:0031333), response to nicotine (GO:0035094), G protein-coupled opioid receptor signaling pathway (GO:0038003), eating behavior (GO:0042755), response to ethanol (GO:0045471), regulation of mitochondrial membrane potential (GO:0051881), regulation of calcium ion transport (GO:0051924), cellular response to growth factor stimulus (GO:0071363), cellular response to hypoxia (GO:0071456), cellular response to toxic substance (GO:0097237), signal transduction (GO:0007165)

GO Molecular Function (7): G protein-coupled opioid receptor activity (GO:0004985), receptor serine/threonine kinase binding (GO:0033612), G protein-coupled enkephalin receptor activity (GO:0038046), 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 (12): plasma membrane (GO:0005886), synaptic vesicle membrane (GO:0030672), dendrite membrane (GO:0032590), presynaptic membrane (GO:0042734), neuron projection (GO:0043005), axon terminus (GO:0043679), spine apparatus (GO:0097444), postsynaptic density membrane (GO:0098839), neuronal dense core vesicle (GO:0098992), membrane (GO:0016020), vesicle (GO:0031982), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-3 pathways:

CategoryPathways
Class A/1 (Rhodopsin-like receptors)1
GPCR downstream signalling1
Signaling by Interleukins1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
G protein-coupled receptor signaling pathway5
G protein-coupled receptor activity3
synaptic membrane2
presynapse2
membrane-bounded organelle2
immune system process1
response to stimulus1
signal transduction1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway1
adenylate cyclase inhibitor activity1
phospholipase C activator activity1
locomotory behavior1
adult behavior1
gene expression1
regulation of gene expression1
negative regulation of macromolecule biosynthetic process1
regulation of protein-containing complex assembly1
negative regulation of cellular component organization1
protein-containing complex assembly1
response to chemical1
feeding behavior1
response to alcohol1
regulation of membrane potential1
calcium ion transport1
regulation of metal ion transport1
response to growth factor1
cellular response to endogenous stimulus1
response to hypoxia1
cellular response to stress1
cellular response to decreased oxygen levels1
response to toxic substance1
cellular response to chemical stimulus1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
G protein-coupled opioid receptor signaling pathway1
signaling receptor binding1
G protein-coupled opioid receptor activity1

Protein interactions and networks

STRING

1202 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
OPRD1PENKP01210849
OPRD1PDYNP01213801
OPRD1COMTP21964731
OPRD1PNOCQ13519711
OPRD1ANKK1Q8NFD2683
OPRD1GPRASP1Q5JY77680
OPRD1POMCP01189661
OPRD1ADH1BP00325594
OPRD1ALDH2P05091531
OPRD1ADH7P40394514
OPRD1VIMP08670507
OPRD1UBAC1Q9BSL1506
OPRD1OXTP01178503
OPRD1ADH6P28332503
OPRD1GABRA6Q16445497

IntAct

35 interactions, top by confidence:

ABTypeScore
ATP2A2CANXpsi-mi:“MI:0914”(association)0.640
OPRD1SLC13A4psi-mi:“MI:0915”(physical association)0.560
OPRD1SMAGPpsi-mi:“MI:0915”(physical association)0.560
OPRD1TMEM237psi-mi:“MI:0915”(physical association)0.560
OPRD1CTXN3psi-mi:“MI:0915”(physical association)0.560
OPRD1RPRMpsi-mi:“MI:0915”(physical association)0.560
OPRD1SLC12A7psi-mi:“MI:0915”(physical association)0.560
OPRD1ATP2A2psi-mi:“MI:0915”(physical association)0.560
OPRD1ATP2A2psi-mi:“MI:0914”(association)0.560
GPRASP1OPRD1psi-mi:“MI:0915”(physical association)0.530
GPRASP1OPRD1psi-mi:“MI:0407”(direct interaction)0.530
OPRD1ATP2A2psi-mi:“MI:0915”(physical association)0.500
OPRD1CANXpsi-mi:“MI:0915”(physical association)0.500
ATP2A2CANXpsi-mi:“MI:0914”(association)0.500
OPRD1psi-mi:“MI:0915”(physical association)0.400
RAMP1OPRD1psi-mi:“MI:0915”(physical association)0.400
RAMP2OPRD1psi-mi:“MI:0915”(physical association)0.400
RAMP3OPRD1psi-mi:“MI:0915”(physical association)0.400
OPRD1SLC13A4psi-mi:“MI:0915”(physical association)0.000
SMAGPOPRD1psi-mi:“MI:0915”(physical association)0.000
CTXN3OPRD1psi-mi:“MI:0915”(physical association)0.000
OPRD1TMEM237psi-mi:“MI:0915”(physical association)0.000
RPRMOPRD1psi-mi:“MI:0915”(physical association)0.000

BioGRID (53): 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), GPRASP1 (Two-hybrid), OPRD1 (Two-hybrid), TMEM237 (Two-hybrid), SLC13A4 (Two-hybrid), SMAGP (Two-hybrid), RPRM (Two-hybrid), CTXN3 (Two-hybrid), OPRD1 (Affinity Capture-Western)

ESM2 similar proteins: A0A287A2K5, F1MV99, O08858, O43193, O77808, O97772, P28646, P30098, P30552, P30553, P30796, P30872, P30873, P30937, P30938, P31391, P32239, P32300, P32307, P32745, P33533, P35346, P35370, P35377, P41143, P41146, P46095, P46627, P47748, P48044, P49660, P51651, P56481, P58406, P79266, P79292, Q49LX5, Q5D0K2, Q6W5G4, Q6YNI2

Diamond homologs: A5PLE7, B0UXR0, B5X337, D4A7K7, F1MV99, O08858, O35210, O35811, O77590, O88634, P11613, P21556, P25025, P25095, P25104, P25106, P26824, P29089, P29754, P29755, P30555, P30556, P30937, P30938, P31391, P32249, P32250, P32300, P33396, P33535, P34976, P35346, P35366, P35372, P35373, P35383, P41143, P41231, P41232, P42866

SIGNOR signaling

42 interactions.

AEffectBMechanism
ADL-5859up-regulatesOPRD1“chemical activation”
PRKCAunknownOPRD1phosphorylation
PRKCDunknownOPRD1phosphorylation
PRKCEunknownOPRD1phosphorylation
GRK2“down-regulates activity”OPRD1phosphorylation
OPRD1“up-regulates activity”GNAI1binding
OPRD1“up-regulates activity”GNAI3binding
OPRD1“up-regulates activity”GNA14binding
MET-enkephalin“up-regulates activity”OPRD1“chemical activation”
alvimopan“down-regulates activity”OPRD1“chemical inhibition”
hydromorphone“up-regulates activity”OPRD1“chemical activation”
nalbuphine“up-regulates activity”OPRD1“chemical activation”
methylnaltrexone“down-regulates activity”OPRD1“chemical inhibition”
POMC“up-regulates activity”OPRD1“chemical activation”
PPBP“down-regulates activity”OPRD1“chemical inhibition”
PDYN“up-regulates activity”OPRD1“chemical activation”
Quadazocine“down-regulates activity”OPRD1“chemical inhibition”
Naltriben“down-regulates activity”OPRD1“chemical inhibition”
beta-Funaltrexamine“down-regulates activity”OPRD1“chemical inhibition”
(4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-6-(phenylmethylene)-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one“down-regulates activity”OPRD1“chemical inhibition”
bremazocine“up-regulates activity”OPRD1“chemical activation”
“Deltorphin B”“up-regulates activity”OPRD1“chemical activation”
Dihydromorphine“up-regulates activity”OPRD1“chemical activation”
Diprenorphine“up-regulates activity”OPRD1“chemical activation”
DPDPE“up-regulates activity”OPRD1“chemical activation”
“Dynorphin A”“up-regulates activity”OPRD1“chemical activation”
“Dynorphin B”“up-regulates activity”OPRD1“chemical activation”
Ethylketocyclazocine“up-regulates activity”OPRD1“chemical activation”
etorphine“up-regulates activity”OPRD1“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance41
Likely benign0
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

851 predictions. Top by Δscore:

VariantEffectΔscore
1:28812608:CCGG:Cdonor_loss1.0000
1:28812609:CGG:Cdonor_loss1.0000
1:28812611:GTGA:Gdonor_loss1.0000
1:28812612:T:Gdonor_loss1.0000
1:28858951:A:AGacceptor_gain1.0000
1:28858951:AAG:Aacceptor_gain1.0000
1:28858952:A:Gacceptor_gain1.0000
1:28859301:GGG:Gdonor_gain1.0000
1:28859302:GGG:Gdonor_gain1.0000
1:28859308:G:GGdonor_gain1.0000
1:28859312:G:GGdonor_gain1.0000
1:28862734:C:CAacceptor_gain1.0000
1:28812606:GTCCG:Gdonor_gain0.9900
1:28812611:G:GGdonor_gain0.9900
1:28858949:CTAA:Cacceptor_loss0.9900
1:28858952:A:Tacceptor_loss0.9900
1:28858953:G:Aacceptor_gain0.9900
1:28858953:G:GTacceptor_gain0.9900
1:28858953:GGT:Gacceptor_gain0.9900
1:28858953:GGTAC:Gacceptor_gain0.9900
1:28859302:GG:Gdonor_gain0.9900
1:28859303:GG:Gdonor_gain0.9900
1:28859303:GGTG:Gdonor_loss0.9900
1:28859304:G:GCdonor_loss0.9900
1:28859304:GTGA:Gdonor_gain0.9900
1:28859306:G:GGdonor_loss0.9900
1:28862732:C:CAacceptor_gain0.9900
1:28862735:G:Aacceptor_gain0.9900
1:28862832:T:TAacceptor_gain0.9900
1:28858950:TAAGG:Tacceptor_gain0.9800

AlphaMissense

2410 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
1:28859153:A:CS143R1.000
1:28859155:T:AS143R1.000
1:28859155:T:GS143R1.000
1:28862972:T:CF270L1.000
1:28862974:C:AF270L1.000
1:28862974:C:GF270L1.000
1:28812570:G:AG63R0.999
1:28812570:G:CG63R0.999
1:28812579:G:CG66R0.999
1:28812584:C:AN67K0.999
1:28812584:C:GN67K0.999
1:28858996:C:AN90K0.999
1:28858996:C:GN90K0.999
1:28858998:T:CL91P0.999
1:28859024:A:CS100R0.999
1:28859026:C:AS100R0.999
1:28859026:C:GS100R0.999
1:28859068:G:CW114C0.999
1:28859068:G:TW114C0.999
1:28859087:T:AC121S0.999
1:28859088:G:AC121Y0.999
1:28859088:G:CC121S0.999
1:28859129:A:CS135R0.999
1:28859131:C:AS135R0.999
1:28859131:C:GS135R0.999
1:28859142:T:AL139H0.999
1:28859142:T:CL139P0.999
1:28859160:A:CD145A0.999
1:28859160:A:TD145V0.999
1:28859163:G:CR146P0.999

dbSNP variants (sampled 300 via entrez): RS1000160351 (1:28813304 C>T), RS1000295585 (1:28821307 T>C), RS1000343641 (1:28861575 G>T), RS1000355615 (1:28850888 A>G), RS1000392698 (1:28814453 C>G), RS1000397528 (1:28861866 C>G,T), RS1000466244 (1:28831521 A>G), RS1000493227 (1:28857500 G>T), RS1000586241 (1:28833951 G>A), RS1000670500 (1:28855416 T>C), RS1000705483 (1:28849669 G>A), RS1000782761 (1:28846645 T>C,G), RS1000795332 (1:28827129 T>C), RS1000906980 (1:28823679 C>T), RS1000914447 (1:28866319 C>T)

Disease associations

OMIM: gene MIM:165195 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST007277_1Tourette syndrome2.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2095149 (SELECTIVITY GROUP), CHEMBL2095151 (SELECTIVITY GROUP), CHEMBL2095181 (PROTEIN FAMILY), CHEMBL236 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

150 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 646,382 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1200531ALFENTANIL HYDROCHLORIDE41,169
CHEMBL19019NALTREXONE434,647
CHEMBL70MORPHINE4128,573
CHEMBL1201149NALTREXONE HYDROCHLORIDE43,278
CHEMBL1718NALOXONE HYDROCHLORIDE44,865
CHEMBL607MEPERIDINE443,837
CHEMBL80NALOXONE438,742
CHEMBL963OXYMORPHONE425,955
CHEMBL100116PENTAZOCINE433,194
CHEMBL1014CANDESARTAN CILEXETIL411,194
CHEMBL1017TELMISARTAN427,457
CHEMBL1018DIENESTROL45,607
CHEMBL104CLOTRIMAZOLE456,325
CHEMBL1096AMLEXANOX44,195
CHEMBL1113AMOXAPINE420,128
CHEMBL1117IDARUBICIN4136,065
CHEMBL114SAQUINAVIR439,899
CHEMBL1186579METHYLNALTREXONE43,390
CHEMBL1200384BETAMETHASONE DIPROPIONATE412,700
CHEMBL1200438TIOCONAZOLE415,162
CHEMBL1201203BENZTROPINE4
CHEMBL1201303PYRVINIUM4
CHEMBL1201304INDOCYANINE GREEN ACID FORM4
CHEMBL1201770METHYLNALTREXONE BROMIDE4
CHEMBL1213351PROPOXYPHENE4
CHEMBL1221SULCONAZOLE4
CHEMBL1237044TRAMADOL4
CHEMBL1242PHENAZOPYRIDINE4
CHEMBL1262OXICONAZOLE4
CHEMBL1292CLOFAZIMINE4

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

PharmGKB clinical annotations

20 annotations.

VariantTypeLevelDrugsPhenotypes
rs204047Dosage3methadone
rs204047Metabolism/PK3methadone
rs2234918Toxicity3buprenorphine;fentanyl;tramadolOpioid-Related Disorders;Physiological sexual disorder
rs2236855Toxicity3heroinHeroin Dependence
rs2236857Toxicity3heroinHeroin Dependence
rs2236861Other3opioidsOpioid-Related Disorders
rs2236861Toxicity3heroinHeroin Dependence
rs2298897Toxicity3heroinHeroin Dependence
rs3766951Toxicity3heroinHeroin Dependence
rs4654327Efficacy3naltrexoneAlcohol abuse
rs4654327Toxicity3heroinHeroin Dependence
rs508448Other3heroinHeroin Dependence
rs529520Efficacy3buprenorphineOpioid-Related Disorders
rs581111Efficacy3oxycodone
rs581111Efficacy4buprenorphineOpioid-Related Disorders
rs678849Toxicity3cocaineCocaine dependence
rs678849Efficacy3methadoneOpioid-Related Disorders
rs678849Efficacy3disulfiramCocaine dependence
rs678849Efficacy3buprenorphineOpioid-Related Disorders
rs797397Metabolism/PK3methadone

PharmGKB variants

29 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs529520OPRD131.501buprenorphine
rs581111OPRD132.002buprenorphine;oxycodone
rs1042114OPRD10.000
rs2236861OPRD131.752opioids;heroin
rs4654327OPRD131.502heroin;naltrexone
rs678849OPRD135.754disulfiram;buprenorphine;methadone;cocaine
rs10753331OPRD10.000
rs2234918OPRD132.751buprenorphine;fentanyl;tramadol
rs533123OPRD10.000
rs2236857OPRD133.501heroin
rs419335OPRD10.000
rs3766951OPRD136.001heroin
rs569356OPRD10.000
rs204047OPRD132.752methadone
rs204055OPRD10.000
rs2236855OPRD133.001heroin
rs760589OPRD10.000
rs2298897OPRD133.001heroin
rs680090OPRD10.000
rs12749204OPRD10.000
rs2298895OPRD10.000
rs508448OPRD132.251heroin
rs204076OPRD10.000
rs204069OPRD10.000
rs6669447OPRD10.000
rs2298896OPRD10.000
rs797397OPRD132.251methadone
rs482387OPRD10.000
rs421300OPRD10.000

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Opioid receptors

Most potent curated ligand interactions (81 total), top 25:

LigandActionAffinityParameter
[3H]naltrindoleAntagonist10.43pKd
UFP-512Agonist10.2pKi
naltribenAntagonist10.0pKi
UFP-505Antagonist9.82pKi
naltrindoleAntagonist9.7pKi
AZD7268Agonist9.52pKi
BW373U86Agonist9.49pKi
[3H][D-Ala2]deltorphin IAgonist9.35pKd
[3H]diprenorphineFull agonist9.3pKi
DSLETFull agonist9.3pKi
diprenorphineFull agonist9.3pKi
DADLEFull agonist9.2pKi
(-)-cyclazocinePartial agonist9.1pKi
ADL5859Agonist9.08pKi
naldemedineAntagonist9.04pKi
(-)-bremazocineFull agonist9.0pKi
TIPPψInverse agonist9.0pKi
quadazocineAntagonist8.9pKi
[3H]DPDPEFull agonist8.9pKd
eluxadolineAntagonist8.89pKi
C6-QuinoPartial agonist8.87pKi
DPDPEFull agonist8.8pKi
etorphineFull agonist8.8pKi
BU08028Partial agonist8.8pKi
deltorphin IIFull agonist8.8pKi

Binding affinities (BindingDB)

872 measured of 1239 human assays (1253 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
32+/-82-[22-cyclopropylmethyl-2,16-dihydroxy-(2S,13R)-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15(25),16,18-heptaen-9-ylcarboxamido]acetic acidKI0.00066 nM
BW373U86KI0.01 nM
CAS_111555-58-9KI0.01 nM
22-cyclopropylmethyl-2,16-dihydroxy-(2S,13R)-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15(25),16,18-heptaene-9-carboxylic acidKI0.016 nM
SN-11EC500.018 nM
4-{[(1S,5R)-8-Allyl-8-aza-bicyclo[3.2.1]oct-(3Z)-ylidene]-phenyl-methyl}-N,N-diethyl-benzamideKI0.025 nM
1N-{3-[22-cyclopropylmethyl-2,16-dihydroxy-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15,17,19(25)-heptaen-11-ylmethyl]phenyl}-2-bromoacetamideKI0.038 nM
SN-23EC500.06 nM
CAS_123924KI0.1 nM
NSC_104911KI0.1 nM
HS464KI0.11 nM
HS510AKI0.12 nM
CHEMBL4066752KI0.154 nM
CHEMBL2113671KI0.16 nM
[D-Ala2-D-Leu5]enkephalinKI0.18 nM
NSC_61677KI0.18 nM
CHEMBL1929365EC500.19 nM
CHEMBL4083940KI0.211 nM
NSC_0KI0.22 nM
CHEMBL4103044EC500.23 nM
7-(2’’-spiroindanyl)naltrexoneKI0.25 nM
22-cyclopropylmethyl-11-ethyl-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15(25),16,18-heptaene-2,16-diolKI0.26 nM
7,7-Spiro analogue ofBuprinorphineEC500.3 nM
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl esterEC500.3 nM
NSC_3034754KI0.3 nM
Tyr-D-Ala-Phe-Glu-Val-Val-GlyNH2KI0.31 nM
(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)-N-[(1R)-1-[({[(2S)-1-oxo-3-phenyl-1-[4-(N-phenylpropanamido)piperidin-1-yl]propan-2-yl]carbamoyl}methyl)carbamoyl]ethyl]propanamideKI0.36 nM
22-cyclopropylmethyl-11-(3-fluoropropyl)-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15(25),16,18-heptaene-2,16-diolKI0.4 nM
HS378KI0.4 nM
2-[22-cyclopropylmethyl-2,16-dihydroxy-(2S,13R)-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15(25),16,18-heptaen-9-ylcarboxamido]-(2R)-butanedioic acidKI0.41 nM
HS531KI0.42 nM
Cis-H-Tyr-c[D-AllylGly-Gly-Phe-D-Allylgly]-OHKI0.43 nM
22-cyclopropylmethyl-11-propyl-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15(25),16,18-heptaene-2,16-diolKI0.44 nM
Deltorphin IKI0.49 nM
CHEMBL477154KI0.49 nM
DSLET-OHKI0.5 nM
4-[((1S,5R)-8-Allyl-8-aza-bicyclo[3.2.1]oct-3-yl)-phenyl-amino]-N,N-diethyl-benzamideKI0.5 nM
1N-[10-hydroxy-4-methyl-14-oxo-(13R,17S)-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7(18),8,10-trien-17-yl]-4-(4-nitrophenyl)-(Z)-2-butenamideKI0.54 nM
(5S,8R,10E,13R)-13-[(2S)-2-amino-3-(4-hydroxyphenyl)propanamido]-5-benzyl-3,6,14-trioxo-1,4,7-triazacyclotetradec-10-ene-8-carboxylic acidKI0.57 nM
CHEMBL4061334KI0.585 nM
(14beta)-17-(cyclopropylmethyl)-18-(1-hydroxy-1-methylethyl)-6-methoxy-18,19-dihydro-4,5-epoxy-6,14-ethenomorphinan-3-olKI0.59 nM
EthylketazocineIC500.6 nM
15-benzyl-4-cyclopropylmethyl-10,17-dihydroxy-(1S,13R,15R,17S)-12-oxa-4-azapentacyclo[9.6.1.01,13.05,17.07,18]octadeca-7,9,11(18)-trien-14-oneKI0.66 nM
CHEMBL4100943EC500.67 nM
(2S)-2-amino-3-(4-hydroxyphenyl)-N-[(1R)-1-[({[(2S)-1-oxo-3-phenyl-1-[4-(N-phenylpropanamido)piperidin-1-yl]propan-2-yl]carbamoyl}methyl)carbamoyl]ethyl]propanamideKI0.69 nM
Morphinan Cyclic Imine analogueIC500.69 nM
CHEMBL1169585KI0.7 nM
CAS_24822630KI0.79 nM
(SSS)-12-Cyclopropylmethyl-13-methyl-12-aza-tricyclo[9.1.1.03,8]trideca-3(8),4,6-trien-6-ol(cyclazocine)KI0.8 nM
3-cyclopropylmethyl-18,18-dimethyl-(15S)-13,16-dioxa-3-azaheptacyclo[13.5.2.12,8.01,6.06,14.07,12.015,19]tricosa-7,9,11-trien-11-olKI0.8 nM

ChEMBL bioactivities

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

pChemblTypeValueUnitMolecule
11.00Ki0.01nMCHEMBL67192
10.89Ki0.013nMNALTRIBEN
10.89Ki0.013nMCHEMBL132420
10.82Ki0.015nMCHEMBL132897
10.80EC500.016nMCHEMBL2151735
10.80Ki0.016nMCHEMBL132420
10.76EC500.01738nMCHEMBL611926
10.74EC500.018nMCHEMBL559518
10.72Ki0.019nMCHEMBL282518
10.70Ki0.02nMCHEMBL477154
10.70Ki0.02nMCHEMBL610529
10.70IC500.02nMCHEMBL443311
10.70EC500.02nMDADLE
10.70EC500.02nMCHEMBL611926
10.70Ki0.02nMNALTREXONE
10.70Ki0.02nMCHEMBL110124
10.68Ki0.021nMCHEMBL3758292
10.64Ki0.023nMCHEMBL67846
10.60Ki0.025nMCHEMBL469815
10.60Ki0.025nMCHEMBL63732
10.52Ki0.03nMNALTRINDOLE
10.52IC500.03nMCHEMBL267027
10.52Ki0.03nMCHEMBL1649946
10.52Ki0.03nMCHEMBL107420
10.51Ki0.031nMNALTRINDOLE
10.51Ki0.031nMCHEMBL458631
10.46Ki0.035nMCHEMBL2375157
10.42Ki0.038nMCHEMBL282518
10.40IC500.04nMDADLE
10.40Ki0.04nMNALTRINDOLE
10.40Ki0.04nMCHEMBL109040
10.40Ki0.04nMNALTREXONE
10.38Ki0.042nMCHEMBL501451
10.33EC500.047nMCHEMBL552308
10.30IC500.05nMCHEMBL2370601
10.22Ki0.06nMCHEMBL611143
10.22EC500.06nMCHEMBL564538
10.21Ki0.062nMNALTRINDOLE
10.19IC500.06457nMCHEMBL1649946
10.19EC500.06457nMCHEMBL1649941
10.17IC500.068nMCHEMBL1939740
10.15IC500.07nMCHEMBL56347
10.15EC500.07079nMCHEMBL1649942
10.15EC500.07nMCHEMBL1649941
10.15EC500.07nMCHEMBL1649942
10.15IC500.071nMCHEMBL1939746
10.15Ki0.07nMNALTRINDOLE
10.10Ki0.08nMCHEMBL2113666
10.10EC500.08nMENKEPHALIN
10.10IC500.08nMCHEMBL469815

PubChem BioAssay actives

2908 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
(3S)-3-[[(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-4-[[(2S)-1-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-oxobutanoic acid277680: Activity at delta opioid receptor assessed as increase in calcium level in CHO cells by aequorin luminescence based calcium assayec50<0.0001uM
N,N-diethyl-4-[phenyl-[(1R,5S)-8-prop-2-enyl-8-azabicyclo[3.2.1]octan-3-ylidene]methyl]benzamide148241: Binding affinity for delta opioid receptorki<0.0001uM
4-[[8-(1,3-benzodioxol-5-ylmethyl)-8-azabicyclo[3.2.1]octan-3-ylidene]-phenylmethyl]-N,N-diethylbenzamide148241: Binding affinity for delta opioid receptorki<0.0001uM
(3S)-2-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-N-[2-(benzylamino)-2-oxoethyl]-3,4-dihydro-1H-isoquinoline-3-carboxamide266690: Binding affinity to delta opioid receptorki<0.0001uM
(3S)-2-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-N-(2-anilino-2-oxoethyl)-3,4-dihydro-1H-isoquinoline-3-carboxamide266690: Binding affinity to delta opioid receptorki<0.0001uM
(3R)-2-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-N-(1H-benzimidazol-2-ylmethyl)-3,4-dihydro-1H-isoquinoline-3-carboxamide1274731: Binding affinity at delta opioid receptor (unknown origin)ki<0.0001uM
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)propanamide273143: Activity at human recombinant delta opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S bindingic50<0.0001uM
(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-one273143: Activity at human recombinant delta opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTP-gamma-S bindingic50<0.0001uM
(1S,14R,15R)-25-(cyclopropylmethyl)-4,25-diazahexacyclo[13.7.3.01,14.03,12.05,10.017,22]pentacosa-3,5,7,9,11,17(22),18,20-octaen-20-ol424039: Agonist activity at human recombinant delta opioid receptor expressed in HEK293 cells by [35S]GTPgammaS binding assayec50<0.0001uM
(4S,7S,13S)-13-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-7-benzyl-3,3,14,14-tetramethyl-6,9,12-trioxo-1,2-dithia-5,8,11-triazacyclotetradecane-4-carboxylic acid1303080: Agonist activity at human DOR expressed in CHO cell membranes after 60 mins by [35S]GTP-gamma-S binding assayec500.0001uM
(E)-N-[(4R,4aS,7aR,12bR)-9-hydroxy-3-methyl-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-yl]-3-(2-methylphenyl)prop-2-enamide269571: Displacement of [3H]Cl-DPDPE from human recombinant DOR expressed in CHO cellski0.0001uM
4-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enylpiperazin-1-yl]-(3-hydroxyphenyl)methyl]-N,N-diethylbenzamide148060: Agonist potency was measured using GTP gamma-[35S] binding assayec500.0001uM
(1R,13S,14S)-24-(cyclopropylmethyl)-4,24-diazahexacyclo[12.7.3.01,13.03,11.05,10.016,21]tetracosa-3(11),5,7,9,16(21),17,19-heptaene-13,19-diol1292340: Displacement of [3H]DPDPE from human delta opioid receptor expressed in CHO cell membraneski0.0001uM
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-iodobenzamide2007423: Binding affinity to human DOR assessed as inhibition constantki0.0001uM
(2R)-N-[(1S,4R,5R,7S)-5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]nonan-7-yl]-2-phenylpropanamide270160: Inverse agonist activity at human cloned delta opioid receptor expressed in CHO cells assessed as inhibition of DPDPE-stimulated [35S]GTP-gamma-S binding in presence of 1 uM GDPic500.0001uM
N-[(1S,4R,5R,7S)-5-(3-hydroxyphenyl)-4-methyl-2-[(E)-3-(2-methylphenyl)prop-2-enyl]-2-azabicyclo[3.3.1]nonan-7-yl]-2-methyl-2-phenylpropanamide270160: Inverse agonist activity at human cloned delta opioid receptor expressed in CHO cells assessed as inhibition of DPDPE-stimulated [35S]GTP-gamma-S binding in presence of 1 uM GDPic500.0001uM
(2S)-6-amino-2-[[(2R)-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]pyrrolidine-2-carbonyl]amino]hexanoic acid226067: Tested for opioid receptor agonistic activity in guinea pig ileumic500.0002uM
1-[[(3S)-2-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-3,4-dihydro-1H-isoquinolin-3-yl]methyl]-3-tert-butylurea148079: Binding affinity at cloned human delta-opioid receptoric500.0002uM
N-[[(3S)-2-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-3,4-dihydro-1H-isoquinolin-3-yl]methyl]benzamide148079: Binding affinity at cloned human delta-opioid receptoric500.0002uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid1798046: Radioligand Labeled Binding Assay and [35S]GTP-gamma-S Binding Assay from Article 10.1021/jm050921q: “Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors.”ki0.0002uM
1-[[(3S)-2-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-3,4-dihydro-1H-isoquinolin-3-yl]methyl]-3-tert-butylthiourea148079: Binding affinity at cloned human delta-opioid receptoric500.0002uM
(3S)-3-[[(2S)-2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]hexanoyl]amino]-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid1798046: Radioligand Labeled Binding Assay and [35S]GTP-gamma-S Binding Assay from Article 10.1021/jm050921q: “Structure-activity relationships of bifunctional peptides based on overlapping pharmacophores at opioid and cholecystokinin receptors.”ki0.0002uM
N-ethyl-4-[(3-hydroxyphenyl)-[8-(thiophen-2-ylmethyl)-8-azabicyclo[3.2.1]octan-3-ylidene]methyl]benzamide150094: In vitro binding affinity towards opioid receptor delta 1ki0.0002uM
N,N-diethyl-4-[phenyl-[(1S,5R)-8-(2-phenylethyl)-8-azabicyclo[3.2.1]octan-3-ylidene]methyl]benzamide148241: Binding affinity for delta opioid receptorki0.0002uM
(3S)-5-(benzenesulfonyl)-20-(cyclopropylmethyl)-21-oxa-5,20-diazahexacyclo[8.7.3.13,9.01,9.02,6.012,17]henicosa-12(17),13,15-trien-15-ol1453588: Displacement of [3H]DPDPE from human delta opioid receptor expressed in CHO cellski0.0002uM
(2S)-2-[[1-[(3R)-2-[2-[[2-[[2-[[1-[(2S)-1-[(2S)-2-[[(2R)-2-amino-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]-4-hydroxypyrrolidine-2-carbonyl]amino]acetyl]amino]-3-thiophen-2-ylpropanoyl]amino]-3-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]propanoyl]-3,4-dihydro-1H-isoquinoline-3-carbonyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carbonyl]amino]-5-carbamimidamidopentanoic acid1247573: Displacement of [3H]DPDPE from human delta opiod receptorki0.0002uM
(3R)-2-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-N-(2-anilino-2-oxoethyl)-3,4-dihydro-1H-isoquinoline-3-carboxamide1274731: Binding affinity at delta opioid receptor (unknown origin)ki0.0002uM
(2S)-3-(4-hydroxy-2,6-dimethylphenyl)-2-[[(2R)-2-[[2-[[(2S)-3-phenyl-2-[2-[(N-propanoylanilino)methyl]piperidin-1-yl]propanoyl]amino]acetyl]amino]propanoyl]amino]propanoic acid1271112: Displacement of [3H]DPDPE from human delta opioid receptor after 180 mins by scintillation counting analysiski0.0002uM
[(3S)-20-(cyclopropylmethyl)-15-hydroxy-5,20-diazahexacyclo[8.7.3.13,9.01,9.02,6.012,17]henicosa-12(17),13,15-trien-5-yl]-(furan-3-yl)methanone1454219: Agonist activity at human recombinant DOR expressed in CHO cells assessed as cAMP accumulationec500.0002uM
(1S,2S,10R,18R)-19-(cyclopropylmethyl)-2-(3-phenylpropoxy)-6-pyrrol-1-yl-11-oxa-8,19-diazahexacyclo[10.9.1.01,10.02,18.04,9.016,22]docosa-4(9),5,7,12,14,16(22)-hexaen-13-ol1669024: Displacement of [3H]-diprenorphine from human delta opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assayki0.0002uM
(1S,2S,10R,18R)-19-(cyclopropylmethyl)-6-(3-methylphenyl)-2-(3-phenylpropoxy)-11-oxa-8,19-diazahexacyclo[10.9.1.01,10.02,18.04,9.016,22]docosa-4(9),5,7,12,14,16(22)-hexaen-13-ol1669028: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hric500.0002uM
(1S,2S,10R,18R)-19-(cyclopropylmethyl)-2-[3-(oxan-4-yl)propoxy]-6-phenyl-11-oxa-8,19-diazahexacyclo[10.9.1.01,10.02,18.04,9.016,22]docosa-4(9),5,7,12,14,16(22)-hexaen-13-ol1669028: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hric500.0002uM
(1S,2S,10R,18R)-19-(cyclopropylmethyl)-6-(5-methyl-1,3,4-oxadiazol-2-yl)-2-(3-phenylpropoxy)-11-oxa-8,19-diazahexacyclo[10.9.1.01,10.02,18.04,9.016,22]docosa-4(9),5,7,12,14,16(22)-hexaen-13-ol1669028: Antagonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as reduction in SNC80-induced [35S]GTPgammaS binding preincubated for 5 mins followed by SNC80 addition and measured after 1 hric500.0002uM
(1R,9R,13R)-10-(cyclopropylmethyl)-1,13-dimethyl-N-[2-(4-phenylphenyl)ethyl]-10-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-triene-4-carboxamide270233: Displacement of [3H]naltrindole from human delta opioid receptor expressed in CHO cellski0.0002uM
(1S,13R,14R)-24-(cyclobutylmethyl)-4,24-diazahexacyclo[12.7.3.01,13.03,11.05,10.016,21]tetracosa-3(11),5,7,9,16(21),17,19-heptaen-19-ol288550: Displacement of [3H]naltrindole from human delta opioid receptor expressed in CHO membraneki0.0002uM
(1S,13R,14R)-24-(cyclopropylmethyl)-4,24-diazahexacyclo[12.7.3.01,13.03,11.05,10.016,21]tetracosa-3(11),5,7,9,16(21),17,19-heptaen-19-ol288550: Displacement of [3H]naltrindole from human delta opioid receptor expressed in CHO membraneki0.0002uM
(1S,9R,10R)-5-amino-20-(cyclopropylmethyl)-6-thia-4,20-diazapentacyclo[8.7.3.01,9.03,7.012,17]icosa-3(7),4,12(17),13,15-pentaen-15-ol288550: Displacement of [3H]naltrindole from human delta opioid receptor expressed in CHO membraneki0.0002uM
N-[(1R,9R,10S,13S,14R)-18-(cyclopropylmethyl)-4-hydroxy-19-oxa-18-azapentacyclo[7.6.3.110,13.01,10.02,7]nonadeca-2(7),3,5-trien-14-yl]-N-methylbenzamide1888743: Agonist activity at human delta opioid receptor expressed in CHO cell membranes assessed as stimulation of [35S]GTPgammaS binding incubated for 2 hrs by scintillation counting methodec500.0002uM
(2R)-1-[(5S,8R,16R)-16-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-benzyl-3,6,10,17-tetraoxo-1,4,7,11-tetrazacycloheptadecane-8-carbonyl]piperidine-2-carboxamide2092929: Agonist activity at human DOR expressed in CHO-K1 cells co-expressing G-alpha15 by calcium mobilization assayec500.0002uM
(2S)-1-[(5S,8R,16R)-16-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-benzyl-3,6,10,17-tetraoxo-1,4,7,11-tetrazacycloheptadecane-8-carbonyl]piperidine-2-carboxamide2092929: Agonist activity at human DOR expressed in CHO-K1 cells co-expressing G-alpha15 by calcium mobilization assayec500.0002uM
(2S)-N-[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]-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]pyrrolidine-2-carboxamide226069: Opioid receptor activity in guinea pig ileum assayic500.0002uM
methyl N-[3-[(R)-[4-(diethylcarbamoyl)phenyl]-[4-(1,3-thiazol-5-ylmethyl)piperazin-1-yl]methyl]phenyl]carbamate640240: Displacement of [I125]deltorphin from delta-opioid receptor overexpressed in human HEK293 cellsic500.0003uM
3-[N-(1-benzylpiperidin-4-yl)-4-(diethylcarbamoyl)anilino]benzamide439321: Displacement of [125I]-[D-Ala2]deltorphin 2 from human cloned delta opioid receptorki0.0003uM
(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)-1-[(3S)-3-(phenylmethoxymethyl)-3,4-dihydro-1H-isoquinolin-2-yl]propan-1-one148079: Binding affinity at cloned human delta-opioid receptoric500.0003uM
1-(1-adamantyl)-3-[[(3S)-2-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-3,4-dihydro-1H-isoquinolin-3-yl]methyl]urea148079: Binding affinity at cloned human delta-opioid receptoric500.0003uM
4-[(4-acetamidophenyl)-[1-[(4-fluorophenyl)methyl]piperidin-4-ylidene]methyl]-N,N-diethylbenzamide643817: Displacement of radiolabeled iodinated deltorphin 2 from delta opioid receptor expressed in HEK293 cell membranesic500.0003uM
(3S)-20-(cyclopropylmethyl)-15-hydroxy-N-phenyl-5,20-diazahexacyclo[8.7.3.13,9.01,9.02,6.012,17]henicosa-12(17),13,15-triene-5-carboxamide1454214: Displacement of [3H]DPDPE from human recombinant DOR expressed in CHO cell membraneski0.0003uM
1-[[(3S)-2-[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-3,4-dihydro-1H-isoquinolin-3-yl]methyl]-3-phenylthiourea148079: Binding affinity at cloned human delta-opioid receptoric500.0003uM
(1S,2S,10R,18R)-8-(cyclohexylmethyl)-19-(cyclopropylmethyl)-2,13-dihydroxy-11-oxa-8,19-diazahexacyclo[10.9.1.01,10.02,18.04,9.016,22]docosa-4(9),12,14,16(22)-tetraen-7-one1181416: Displacement of [3H]Cl-DPDPE from human recombinant delta opioid receptor expressed in CHO cell membranes after 60 mins by scintillation counting methodki0.0003uM
N-[[1-[[(5R)-5-amino-5,6,7,8-tetrahydronaphthalen-2-yl]methyl]piperidin-4-yl]methyl]-N-phenylpropanamide1247886: Displacement of [3H] DAMGO from human delta opioid receptoric500.0003uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

ChemicalActions (top 5)PubMed papers
Enkephalin, D-Penicillamine (2,5)-increases activity, decreases reaction, affects binding, affects reaction3
Benzo(a)pyreneaffects methylation, increases methylation2
Valproic Aciddecreases expression, increases methylation, affects cotreatment2
methylmercuric chloridedecreases expression1
bisphenol Adecreases methylation1
ethyl-p-hydroxybenzoatedecreases expression1
S-(1,2-dichlorovinyl)cysteineaffects cotreatment, decreases expression1
CGP 52608affects binding, increases reaction1
7-hydroxymitragynineaffects binding, affects reaction, increases activity1
Resveratrolaffects cotreatment, decreases expression1
Buprenorphineaffects binding, decreases reaction1
Dynorphinsincreases activity1
Enkephalin, Leucineincreases activity1
Estradiolincreases expression1
Hydralazineaffects cotreatment, decreases expression1
Lipopolysaccharidesaffects cotreatment, decreases expression1
Morphineincreases expression, affects binding, increases reaction, increases phosphorylation, decreases reaction1
Oils, Volatileaffects binding1
Paraquatdecreases expression1
Plant Extractsaffects cotreatment, decreases expression1
Rotenonedecreases expression1
Enkephalin, Leucine-2-Alanineincreases activity, affects binding, decreases reaction1
Acrylamidedecreases expression1
Endocannabinoidsdecreases reaction, increases activity, affects binding1

ChEMBL screening assays

2150 unique, capped per target: 1454 binding, 689 functional, 7 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1794484FunctionalPUBCHEM_BIOASSAY: Luminescence-based cell-based high throughput dose response assay for agonists of heterodimerization of the mu 1 (OPRM1) and delta 1 (OPRD1) opioid receptors. (Class of assay: confirmatory) [Related pubchem assays (depositPubChem BioAssay data set
CHEMBL4145313BindingDisplacement of [3H]-diprenorphine from human mu-delta opioid receptor heterodimer expressed in CHO cell membranes at high site fraction after 80 mins by scintillation counting analysis relative to controlSynthesis and Evaluation of a Novel Bivalent Selective Antagonist for the Mu-Delta Opioid Receptor Heterodimer that Reduces Morphine Withdrawal in Mice. — J Med Chem
CHEMBL3239405ADMETAgonist activity at GFP-fused delta opioid receptor (unknown origin) expressed in HEK293 cells assessed as recruitment of beta-arrestin-2 after 10 mins by BRET assayEndomorphin analogues with mixed μ-opioid (MOP) receptor agonism/δ-opioid (DOP) receptor antagonism and lacking β-arrestin2 recruitment activity. — Bioorg Med Chem

Cellosaurus cell lines

9 cell lines: 5 cancer cell line, 3 spontaneously immortalized cell line, 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_1661ZR-75-30Cancer cell lineFemale
CVCL_C0TCACTOne OPRD1Transformed cell lineFemale
CVCL_H483CHO-K1/OPRD1/Galpha15Spontaneously immortalized cell lineFemale
CVCL_KV59cAMP Hunter CHO-K1 OPRD1 GiSpontaneously immortalized cell lineFemale
CVCL_KY68PathHunter CHO-K1 OPRD1 beta-arrestinSpontaneously immortalized cell lineFemale
CVCL_LA94PathHunter U2OS OPRD1 Activated GPCR InternalizationCancer cell lineFemale
CVCL_LA95PathHunter U2OS OPRD1 beta-arrestinCancer cell lineFemale
CVCL_LA96PathHunter U2OS OPRD1 beta-arrestin-1Cancer cell lineFemale
CVCL_ZL07Tango OPRD1-bla U2OSCancer cell lineFemale

Clinical trials (associated diseases)

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

About this page

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

Generated
Atlas version
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Sources 80

This page pulls from 80 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot