OPRL1

Summary

OPRL1 (opioid related nociceptin receptor 1, HGNC:8155) is a protein-coding gene on chromosome 20q13.33, encoding Nociceptin receptor (P41146). G-protein coupled opioid receptor that functions as a receptor for the endogenous neuropeptide nociceptin.

The protein encoded by this gene is a member of the 7 transmembrane-spanning G protein-coupled receptor family, and functions as a receptor for the endogenous, opioid-related neuropeptide, nociceptin/orphanin FQ. This receptor-ligand system modulates a variety of biological functions and neurobehavior, including stress responses and anxiety behavior, learning and memory, locomotor activity, and inflammatory and immune responses. A promoter region between this gene and the 5’-adjacent RGS19 (regulator of G-protein signaling 19) gene on the opposite strand functions bi-directionally as a core-promoter for both genes, suggesting co-operative transcriptional regulation of these two functionally related genes. Alternatively spliced transcript variants have been described 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 4987 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 59 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_182647

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8155
Approved symbol	OPRL1
Name	opioid related nociceptin receptor 1
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	NOCIR, ORL1, OOR, KOR-3, NOPr, PNOCR
Ensembl gene	ENSG00000125510
Ensembl biotype	protein_coding
OMIM	602548
Entrez	4987

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 17 protein_coding

ENST00000336866, ENST00000349451, ENST00000355631, ENST00000672146, ENST00000879249, ENST00000879250, ENST00000879251, ENST00000879252, ENST00000879253, ENST00000879254, ENST00000879255, ENST00000879256, ENST00000921128, ENST00000942720, ENST00000942721, ENST00000942722, ENST00000942723

RefSeq mRNA: 6 — MANE Select: NM_182647 NM_000913, NM_001200019, NM_001318853, NM_001318854, NM_001318855, NM_182647

CCDS: CCDS13556, CCDS93075

Canonical transcript exons

ENST00000336866 — 5 exons

Exon	Start	End
ENSE00001845714	64080082	64080352
ENSE00003847756	64098276	64100633
ENSE00003980002	64091966	64092116
ENSE00003980003	64097802	64098157
ENSE00003980015	64092688	64092953

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 81.76.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0070 / max 89.1662, expressed in 548 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185928	0.7772	390
185931	0.7594	98
185932	0.1988	75
185929	0.1758	73
185935	0.0303	17
185933	0.0290	21
185934	0.0283	16
185930	0.0082	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	81.76	gold quality
superior frontal gyrus	UBERON:0002661	80.25	gold quality
right frontal lobe	UBERON:0002810	79.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.38	gold quality
leukocyte	CL:0000738	79.23	gold quality
monocyte	CL:0000576	79.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	78.72	gold quality
granulocyte	CL:0000094	77.69	gold quality
frontal cortex	UBERON:0001870	77.64	gold quality
primary visual cortex	UBERON:0002436	77.48	gold quality
cortical plate	UBERON:0005343	76.35	gold quality
cerebral cortex	UBERON:0000956	76.29	gold quality
nucleus accumbens	UBERON:0001882	76.19	gold quality
hypothalamus	UBERON:0001898	76.02	gold quality
prefrontal cortex	UBERON:0000451	75.89	gold quality
anterior cingulate cortex	UBERON:0009835	74.51	gold quality
caudate nucleus	UBERON:0001873	73.25	gold quality
putamen	UBERON:0001874	72.97	gold quality
brain	UBERON:0000955	71.50	gold quality
stromal cell of endometrium	CL:0002255	71.18	gold quality
temporal lobe	UBERON:0001871	70.61	gold quality
amygdala	UBERON:0001876	70.28	gold quality
Ammon’s horn	UBERON:0001954	69.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.59	gold quality
spleen	UBERON:0002106	69.22	gold quality
substantia nigra	UBERON:0002038	68.87	gold quality
right hemisphere of cerebellum	UBERON:0014890	67.94	gold quality
left testis	UBERON:0004533	67.40	gold quality
ventricular zone	UBERON:0003053	67.39	gold quality
bone marrow cell	CL:0002092	67.25	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting OPRL1, 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-4425	100.00	67.59	1049
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-31-5P	98.58	68.35	1239

Literature-anchored findings (GeneRIF, showing 38)

• Data show that the dynamic cycle between nociceptin receptor activation, internalization and recycling determines the activity of this receptor on the cell surface. (PMID:12568343)
• Nociceptin receptor mRNA is expressed in human trigeminal ganglia but not in basilar arteries. (PMID:12576178)
• OP4/ORL1 receptor is synthesized and functionally expressed in vascular endothelial cells, presumably as a starting point for some vasoactive mechanism(s). (PMID:14660000)
• Nociceptin-induced receptor endocytosis mainly occurred via clathrin-coated pits. Mainly internalized through the endosome compartment. Receptor phosphorylation necessary for internalization. (PMID:15016723)
• Results suggest that opioid receptor-like (ORL1) receptor utilizes both G(oA) and G(oB) for signal transduction. (PMID:16800795)
• The ORL-1 receptor is expressed by all subtypes of leukocytes; its function is not the modulation of cytokine production and requires further studies. (PMID:16807742)
• Polymorphism not associated with panic disorder. (PMID:17167337)
• molecular analysis of the nociceptin receptor and its ligand complexes (PMID:17456499)
• We analyzed 10 single nucleotide polymorphisms (SNPs) in OPRL1 and 15 SNPs in PNOC in a sample of 1923 European Americans from 219 multiplex alcohol dependent families (PMID:17910740)
• However, there was evidence in support of LD between the OLR1+1071, the OLR1+1073, and the rs669 SNPs, with T-C-A haplotype being associated with significant increased risk of AD. (PMID:18191876)
• Human CD14(+) monocytes expresses the mRNA for ORL1. The ORL1/nociceptin system plays a role in regulating chemotactic responses of leukocytes through chemokine suppression. (PMID:18247127)
• We genotyped 15 single nucleotide polymorphisms (SNPs) spanning the OPRL1 locus and found that SNP rs6010718 was significantly associated with both Type I and Type II alcoholics. (PMID:18269382)
• existence of a cross-talk between NOP and kainate receptors, leading to an interplay between glutamate and N/OFQ circuits (PMID:18286384)
• Our results support the concept postulating that chronic ethanol consumption and withdrawal downregulate the PNOC/OPRL1 system, which critically controls alcohol intake. (PMID:19501074)
• study provides evidence for an association of two variants of the OPRL1 gene, rs6090041 and rs6090043, with vulnerability to develop opiate addiction, suggesting a role for nociceptin/orphanin FQ receptor in the development of opiate addiction (PMID:20032820)
• OPRL1 expression was 1.83 times higher in vitiligo involved skin when compared to healthy control skin. (PMID:20888736)
• Our studies reported here show that ORL1 exhibits the ability to cross-desensitize CXCR4 in both primary leukocytes and hematopoetic cell lines (PMID:21656184)
• The presence of at least one C allele is associated with a decreased expression of OLR1 mRNA in the absence of hsa-miR369-3p de-regulation (PMID:21709374)
• crystal structure of human NOP (also known as ORL-1), solved in complex with the peptide mimetic antagonist compound-24 (PMID:22596163)
• Decreased plasma nociceptin/orphanin FQ is closely associated with the presence of acute cardiovascular disease, and the severity of symptoms has a significant negative correlation with the N/OFQ levels. (PMID:22849833)
• Dominant-positive Arrestin3 but not Arrestin2 was sufficient to rescue NOPR-S363A internalization and JNK signaling. (PMID:23086955)
• Oprl1 is associated with amygdala function, fear processing, and posttraumatic stress disorder symptoms. (PMID:23740899)
• Overall methylation levels in the promoter regions of three genes (ALDH1A1, OPRL1 and RGS19) are elevated in subjects who were exposed to childhood adversity. (PMID:23799031)
• Data suggest that nociceptin and nociceptin receptor evolved as one of 4 opioid receptor systems in vertebrates; this system exhibits both analgesic and hyperalgesic effects. [REVIEW] (PMID:25677768)
• Opioid neuropeptide systems are important mediators of ovarian steroid signaling that regulate reproduction in female; data suggest that nociceptin and nociceptin receptor system in arcuate nucleus of hypothalamus is such a system. [REVIEW] (PMID:25677773)
• Data suggest that the nociceptin/nociceptin receptor system is involved in modulation of the immune response and in pathogenesis of autoimmune diseases. [REVIEW] (PMID:25677775)
• Data suggest that the nociceptin/nociceptin receptor system is involved in modulation of psychological and inflammatory stress responses and in pathogenesis of anxiety. [REVIEW] (PMID:25677776)
• Data suggest that interaction between the nociceptin/nociceptin receptor system and the orexin/orexin receptor system in neurons of the hypothalamus positively and negatively modulate complex and integrated responses to stress. [REVIEW] (PMID:25677777)
• Data suggest that nociceptin/nociceptin receptor signaling in neurons of the hippocampus modulate learning and memory. [REVIEW] (PMID:25677778)
• Study presents evidence suggesting that the PNOC and OPRL1 are dysregulated in suicide completers, thereby potentially contributing to impaired emotional and behavioral control and, ultimately, to the suicidal crisis (PMID:26349406)
• The results of in vitro Ala scanning analyses revealed that the labeled residues were Cys59 in TM1, Cys215 and Cys231 in TM5, and Cys310 in TM7. The present study has provided a novel method of Cys(Npys)-affinity labeling for identification of the ligand-binding sites in the ORL1 receptor. (PMID:27271345)
• The rs2229205 SNP in the OPRL1 gene may be a genetic factor that contributes to individual differences in the vulnerability to smoking in Japanese individuals (PMID:27490265)
• Low methylation levels in intron 1 of OPRL1 are associated with higher psychosocial stress and higher frequency of binge drinking, an effect mediated by OPRL1 methylation: in individuals with low methylation of OPRL1, frequency of binge drinking is associated with stronger BOLD response in the ventral striatum during reward anticipation. (PMID:29197086)
• Nociceptin receptor ORL1 increases the cell surface expression of reticulon 4 receptor (NgR1) in HEK293T cells. (PMID:29615517)
• the present findings on OPRM1 and OPRL1 methylation together with our previous study on OPRK1 and OPRD1, suggest an epigenetic involvement of the opioid system in AD, and a potential diagnostic value of opioid receptor methylation for AD. (PMID:30152845)
• NOP-R is expressed on epidermal keratinocytes in pachyonychia congenita. Robust NOP-R expression was detected in epidermal keratinocytes and in a subset of PGP9.5+ fibers in both epidermis and dermis. NOP-R expression in keratinocytes was reduced in -affected plantar skin vs unaffected skin. Expression occurred in dermal NFH+ myelinated fibers in all groups, and SP+ fibers, but few CGRP+ fibers co-expressed it. (PMID:30255608)
• Decreased Nociceptin Receptors Are Related to Resilience and Recovery in College Women Who Have Experienced Sexual Violence. Decreased midbrain and cerebellum nociceptin receptors are associated with less severe PTSD symptoms. Medications that target nociceptin should be explored to prevent and treat PTSD. (PMID:30954231)
• Heterodimerization of apelin and opioid receptor-like 1 receptors mediates apelin-13-induced G protein biased signaling. (PMID:37364634)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	oprl1	ENSDARG00000071209
mus_musculus	Oprl1	ENSMUSG00000027584
rattus_norvegicus	Oprl1	ENSRNOG00000016768
drosophila_melanogaster	Rh7	FBGN0036260
caenorhabditis_elegans	trhr-1	WBGENE00016265

Paralogs (17): OPRK1 (ENSG00000082556), OPRM1 (ENSG00000112038), KISS1R (ENSG00000116014), OPRD1 (ENSG00000116329), 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

Nociceptin receptor — P41146 (reviewed: P41146)

Alternative names: Kappa-type 3 opioid receptor, Orphanin FQ receptor

All UniProt accessions (2): P41146, A0A5F9ZI64

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled opioid receptor that functions as a receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin.

Subcellular location. Cell membrane. Cytoplasmic vesicle.

Tissue specificity. Detected in blood leukocytes.

Post-translational modifications. Phosphorylation at Ser-363 requires GRK3.

Induction. By phytohemagglutinin (PHA).

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

Isoforms (2)

UniProt ID	Names	Canonical?
P41146-1	1	yes
P41146-2	2, KOR-3D

RefSeq proteins (6): NP_000904, NP_001186948, NP_001305782, NP_001305783, NP_001305784, NP_872588* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001418	Opioid_rcpt	Family
IPR001420	X_opioid_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (49 total): mutagenesis site 10, helix 10, topological domain 8, transmembrane region 7, glycosylation site 3, strand 3, site 2, chain 1, modified residue 1, lipid moiety-binding region 1, disulfide bond 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5DHG	X-RAY DIFFRACTION	3
5DHH	X-RAY DIFFRACTION	3
4EA3	X-RAY DIFFRACTION	3.01
8F7X	ELECTRON MICROSCOPY	3.28

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41146-F1	82.22	0.52

Antibody-complex structures (SAbDab): 1 — 8F7X

Functional residue map

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

Catalytic / active sites (2): 110 (important for g protein-mediated signaling); 130 (important for g protein-mediated signaling)

Post-translational modifications (2): 363, 334

Disulfide bonds (1): 123–200

Glycosylation sites (3): 21, 28, 39

Mutagenesis-validated functional residues (10):

Position	Phenotype
107	impairs g protein-mediated inhibition of adenylate cyclase.
110	abolishes g protein-mediated inhibition of adenylate cyclase. no effect on antagonist-mediated inhibition of g protein-m
130	abolishes g protein-mediated inhibition of adenylate cyclase. abolishes antagonist-mediated inhibition of g protein-medi
131	impairs g protein-mediated inhibition of adenylate cyclase.
280	impairs g protein-mediated inhibition of adenylate cyclase.
309	mildly impairs g protein-mediated inhibition of adenylate cyclase. abolishes antagonist-mediated inhibition of g protein
337	no effect on ligand-mediated internalization; when associated with a-346 and a-351.
346	no effect on ligand-mediated internalization; when associated with a-337 and a-351.
351	no effect on ligand-mediated internalization; when associated with a-337 and a-346.
363	impairs ligand-mediated internalization.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 106 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_SENSORY_PERCEPTION_OF_PAIN, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_NEURON_NEURON_SYNAPTIC_TRANSMISSION, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_SYNAPTIC_SIGNALING, MORF_RAP1A, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, GOBP_SENSORY_PERCEPTION, GOBP_ADENYLATE_CYCLASE_INHIBITING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOCC_NEURON_PROJECTION, KANG_IMMORTALIZED_BY_TERT_DN

GO Biological Process (10): 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), neuron-neuron synaptic transmission (GO:0007270), sensory perception (GO:0007600), sensory perception of pain (GO:0019233), calcium-mediated signaling (GO:0019722), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled opioid receptor signaling pathway (GO:0038003)

GO Molecular Function (6): nociceptin receptor activity (GO:0001626), G protein-coupled receptor activity (GO:0004930), neuropeptide binding (GO:0042923), G protein-coupled opioid receptor activity (GO:0004985), protein binding (GO:0005515), G protein-coupled peptide receptor activity (GO:0008528)

GO Cellular Component (5): plasma membrane (GO:0005886), cytoplasmic vesicle (GO:0031410), neuron projection (GO:0043005), synaptic membrane (GO:0097060), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	4
G protein-coupled receptor activity	3
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
phospholipase C activator activity	1
chemical synaptic transmission	1
nervous system process	1
sensory perception	1
intracellular signaling cassette	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
G protein-coupled opioid receptor activity	1
G protein-coupled peptide receptor activity	1
transmembrane signaling receptor activity	1
peptide binding	1
G protein-coupled opioid receptor signaling pathway	1
binding	1
peptide receptor activity	1
membrane	1
cell periphery	1
cytoplasm	1
intracellular vesicle	1
plasma membrane bounded cell projection	1
synapse	1
plasma membrane region	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

20 interactions, top by confidence:

A	B	Type	Score
OPRL1	CERS6	psi-mi:“MI:0915”(physical association)	0.630
CERS6	OPRL1	psi-mi:“MI:0915”(physical association)	0.630
OPRL1	GPRASP1	psi-mi:“MI:0407”(direct interaction)	0.440
OPRL1	PNOC	psi-mi:“MI:0915”(physical association)	0.400
OPRL1	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	OPRL1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	OPRL1	psi-mi:“MI:0915”(physical association)	0.400
OPRL1	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
OPRL1	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	OPRL1	psi-mi:“MI:0915”(physical association)	0.400
DNAJC30	OPRL1	psi-mi:“MI:0915”(physical association)	0.370
PLLP	OPRL1	psi-mi:“MI:0915”(physical association)	0.370
SLC31A2	OPRL1	psi-mi:“MI:0915”(physical association)	0.370
HLA-C	OPRL1	psi-mi:“MI:0915”(physical association)	0.370
OPRL1	METTL15	psi-mi:“MI:0914”(association)	0.350

BioGRID (105): OPRL1 (Synthetic Growth Defect), OPRL1 (Affinity Capture-RNA), OPRM1 (Affinity Capture-Western), OPRL1 (Affinity Capture-Western), OPRL1 (Reconstituted Complex), OPRM1 (Reconstituted Complex), OPRL1 (Affinity Capture-Western), CERS6 (Two-hybrid), DNAJC30 (Two-hybrid), PLLP (Two-hybrid), SLC31A2 (Two-hybrid), HLA-C (Two-hybrid), PNOC (Reconstituted Complex), OPRL1 (Affinity Capture-RNA), ADCK1 (Affinity Capture-MS)

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: A0T2N3, F1MV99, O00155, O00590, O08707, O08858, O09027, O35210, O77590, O88410, O89039, O97666, P0C5I1, P0C7U4, P11613, P21109, P25024, P25025, P25095, P25104, P25106, P29089, P29754, P29755, P30555, P30556, P30680, P30874, P30875, P30935, P30936, P30937, P30938, P31391, P32303, P32745, P33396, P33535, P34976, P34993

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
OPRL1	“up-regulates activity”	GNAI1	binding
OPRL1	“up-regulates activity”	GNAI3	binding
OPRL1	“up-regulates activity”	GNAO1	binding
OPRL1	“up-regulates activity”	GNAZ	binding
OPRL1	“up-regulates activity”	GNA14	binding
nociceptin	“up-regulates activity”	OPRL1	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1244 predictions. Top by Δscore:

Variant	Effect	Δscore
20:64080405:GGT:G	donor_gain	1.0000
20:64098157:GGTC:G	donor_loss	1.0000
20:64098158:G:C	donor_loss	1.0000
20:64098159:T:A	donor_loss	1.0000
20:64098273:CA:C	acceptor_loss	1.0000
20:64098274:A:AG	acceptor_gain	1.0000
20:64098274:A:T	acceptor_loss	1.0000
20:64098275:G:C	acceptor_loss	1.0000
20:64098275:G:GA	acceptor_gain	1.0000
20:64098275:GA:G	acceptor_gain	1.0000
20:64098275:GAGAT:G	acceptor_gain	1.0000
20:64080325:G:GT	donor_gain	0.9900
20:64080407:T:G	donor_gain	0.9900
20:64083817:CCCG:C	donor_gain	0.9900
20:64092114:GAA:G	donor_gain	0.9900
20:64092117:G:GG	donor_gain	0.9900
20:64098146:TC:T	donor_gain	0.9900
20:64098271:T:TA	acceptor_gain	0.9900
20:64098273:CAG:C	acceptor_gain	0.9900
20:64098274:AGA:A	acceptor_gain	0.9900
20:64098275:GAG:G	acceptor_gain	0.9900
20:64098275:GAGA:G	acceptor_gain	0.9900
20:64080340:G:GT	donor_gain	0.9800
20:64080350:C:T	donor_gain	0.9800
20:64080383:G:GG	donor_gain	0.9800
20:64080387:GCCGC:G	donor_gain	0.9800
20:64080404:GGGT:G	donor_gain	0.9800
20:64083810:CGCCT:C	donor_loss	0.9800
20:64083811:GCCTC:G	donor_loss	0.9800
20:64083812:CCTCA:C	donor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000129702 (20:64082597 G>C), RS1000303933 (20:64083516 G>A), RS1000325653 (20:64097191 TCAC>T), RS1000348314 (20:64089464 C>T), RS1000441807 (20:64096591 C>T), RS1000510928 (20:64096896 C>A,T), RS1000663489 (20:64095500 A>G), RS1000784964 (20:64095309 A>G), RS1000817515 (20:64082360 G>C), RS1000967897 (20:64096581 C>G), RS1001029532 (20:64088471 G>C), RS1001179295 (20:64088093 C>T), RS1001250606 (20:64082770 GGCTTCCTTTTGTACT>G), RS1001296843 (20:64089612 T>C), RS1001351437 (20:64097740 C>A,T)

Disease associations

OMIM: gene MIM:602548 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002989_13	LDL peak particle diameter (total fat intake interaction)	7.000000e-06
GCST004602_237	Mean corpuscular volume	8.000000e-09
GCST007001_16	Cerebrospinal AB1-42 levels in normal cognition	3.000000e-07
GCST007931_15	Medication use (HMG CoA reductase inhibitors)	1.000000e-16
GCST009602_87	Metabolic syndrome	4.000000e-08
GCST010173_151	Triglyceride levels	9.000000e-09
GCST010242_268	HDL cholesterol levels	2.000000e-09
GCST010244_275	Triglyceride levels	4.000000e-16
GCST90002388_588	Lymphocyte count	3.000000e-09
GCST90002390_679	Mean corpuscular hemoglobin	2.000000e-13
GCST90002392_120	Mean corpuscular volume	5.000000e-15
GCST90002396_72	Mean reticulocyte volume	1.000000e-12
GCST90002397_294	Mean spheric corpuscular volume	1.000000e-22
GCST90020024_809	A body shape index	2.000000e-13
GCST90020025_1765	Waist-to-hip ratio adjusted for BMI	4.000000e-20
GCST90020025_1767	Waist-to-hip ratio adjusted for BMI	5.000000e-08
GCST90020027_361	Waist-hip index	1.000000e-20
GCST90020029_157	Waist circumference adjusted for body mass index	1.000000e-13

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0007677	LDL peak particle diameter measurement
EFO:0007678	total fat intake measurement
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0000195	metabolic syndrome
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004587	lymphocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2014 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 92,970 (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
CHEMBL46516	FLUSPIRILENE	4	41,239
CHEMBL511142	BUPRENORPHINE	4	51,203
CHEMBL2364605	CEBRANOPADOL	3	252
CHEMBL421665	FLUPERAMIDE	2	275
CHEMBL427683	ORGANON	2	1

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2229205	Dosage	3	methadone	Heroin Dependence
rs6090041	Toxicity	3	opioids	Opioid-Related Disorders
rs6090043	Toxicity	3	opioids	Opioid-Related Disorders

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6090041	OPRL1, RGS19	3	0.50	1	opioids
rs6090043	LKAAEAR1, OPRL1	3	0.50	1	opioids
rs2229205	OPRL1	3	2.25	1	methadone
rs2295448	OPRL1		0.00	0
rs6010717	LKAAEAR1, OPRL1		0.00	0
rs7271530	OPRL1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Opioid receptors

Most potent curated ligand interactions (37 total), top 25:

Ligand	Action	Affinity	Parameter
UFP-102	Full agonist	10.7	pKd
N/OFQ-NH2	Full agonist	10.4	pKi
N/OFQ-(1-13)-NH2	Full agonist	10.4	pKi
PWT2-N/OFQ	Agonist	10.3	pKi
[3H]N/OFQ	Full agonist	10.2	pKd
UFP-101	Antagonist	10.2	pKi
[3H]Leu-N/OFQ	Full agonist	10.2	pKd
[(pF)Phe4]N/OFQ-(1-13)-NH2	Agonist	10.12	pEC50
[3H]Tyr14-N/OFQ	Full agonist	10.0	pKd
compound 24 [PMID: 16451050]	Antagonist	10.0	pIC50
LY2940094	Antagonist	10.0	pKi
nociceptin/orphanin FQ	Agonist	9.8	pEC50
UFP-112	Full agonist	9.71	pEC50
SB 612111	Antagonist	9.7	pIC50
[Arg14Lys15]N/OFQ	Full agonist	9.5	pKi
MCOPPB	Full agonist	9.41	pEC50
[F/G]N/OFQ-(1-13)-NH2	Partial agonist	9.2	pKi
AT-403	Agonist	8.96	pKi
AT-076	Antagonist	8.76	pKi
Ac-RYYRWK-NH2	Agonist	8.68	pEC50
AT-121	Partial agonist	8.44	pKi
[Nphe1]N/OFQ-(1-13)-NH2	Antagonist	8.4	pKi
sunobinop	Partial agonist	8.39	pEC50
J-113397	Antagonist	8.3	pIC50
JTC-801	Antagonist	8.1	pKi

Binding affinities (BindingDB)

378 measured of 407 human assays (437 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CAS_170713-75-4	KI	0.18 nM
FGGFTGARKSARK	KI	0.2 nM
arylpyrazole, 31	EC50	0.31 nM
N-[4-(dimethylamino)-1,4-diphenylcyclohexyl]-3-fluoro-N-methylbenzamide	KI	0.35 nM	US-9403767: Substituted 4-aminocyclohexane derivatives
N-[[4-(dimethylamino)-1-methyl-4-phenylcyclohexyl]methyl]-N-methyl-1H-indol-3-amine	KI	0.4 nM	US-9403767: Substituted 4-aminocyclohexane derivatives
Ac-RYYRWKKKKKKK-NH2	KI	0.5 nM
benzimidazole analogue, 7j	EC50	0.55 nM
benzimidazole analogue, 7p	EC50	0.59 nM
benzimidazole-based antagonist, 1	EC50	0.65 nM
benzimidazole analogue, 7e	EC50	0.72 nM
(5S)-5-[[1-[(1R,5S)-9-[(1S,6R)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzimidazol-2-yl]methyl]pyrrolidin-2-one	KI	0.8 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
2-Cyclohexylcarbonylbenzimidazole, 7e	IC50	0.8 nM
N-(4-cyano-3-methylsulfanyl-1H-pyrazol-5-yl)-2-[1-(cyclobutylmethyl)-8-(dimethylamino)-2-oxo-8-phenyl-1,3-diazaspiro[4.5]decan-3-yl]acetamide	KI	0.8 nM	US-10807989: 3-(carboxymethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives
benzimidazole analogue, 7h	IC50	0.81 nM
benzimidazole analogue, 7m	EC50	0.9 nM
benzimidazole analogue, 7o	EC50	0.91 nM
1-[(1R,5S)-9-[(1S,6R)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-2-(5-methoxypyrazin-2-yl)benzimidazole	KI	0.92 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
arylpyrazole, 28	EC50	1 nM
benzimidazole analogue, 7k	IC50	1 nM
[4-[(1R,5S)-9-[(1S,5R)-7-methyl-3-bicyclo[3.3.1]nonanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3-oxoquinoxalin-2-yl]phosphonic acid	KI	1 nM	US-9598447: Phosphorus-substituted quinoxaline-type piperidine compounds and uses thereof
[4-(dimethylamino)-4-phenyl-1-(4-phenylbutyl)cyclohexyl]methanol	KI	1.1 nM	US-9403767: Substituted 4-aminocyclohexane derivatives
arylpyrazole, 30	IC50	1.1 nM
benzimidazole analogue, 7c	EC50	1.1 nM
benzimidazole analogue, 7g	EC50	1.1 nM
4-[(1R,5S)-9-[(1S,5R)-7-methyl-3-bicyclo[3.3.1]nonanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3-oxoquinoxaline-2-carboxylic acid	KI	1.1 nM	US-8476271: Substituted-quinoxaline-type bridged-piperidine compounds as ORL-1 modulators
1-[(1R,5S)-9-[(1S,6R)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-2-pyrazin-2-ylbenzimidazole	KI	1.15 nM	US-9598411: Substituted benzimidazole-type piperidine compounds and uses thereof
N-[4-(dimethylamino)-1,4-diphenylcyclohexyl]-N-methyl-3-(trifluoromethyl)benzamide	KI	1.2 nM	US-9403767: Substituted 4-aminocyclohexane derivatives
N-[4-(dimethylamino)-1,4-diphenylcyclohexyl]-4-methoxy-N-methylbenzamide	KI	1.2 nM	US-9403767: Substituted 4-aminocyclohexane derivatives
(E)-N-[[4-(dimethylamino)-4-(3-fluorophenyl)-1-methylcyclohexyl]methyl]-2-phenylethenesulfonamide	KI	1.24 nM	US-9403767: Substituted 4-aminocyclohexane derivatives
4-chloro-N-[[4-(dimethylamino)-1-methyl-4-phenylcyclohexyl]methyl]benzenesulfonamide	KI	1.25 nM	US-9403767: Substituted 4-aminocyclohexane derivatives
2-Cyclohexylcarbonylbenzimidazole, 7c	EC50	1.3 nM
3-benzyl-1-[4-(dimethylamino)-1,4-diphenylcyclohexyl]-1-methylurea	KI	1.5 nM	US-9403767: Substituted 4-aminocyclohexane derivatives
(E)-N-[[4-(dimethylamino)-4-(3-fluorophenyl)-1-methylcyclohexyl]methyl]-3-phenylprop-2-enamide	KI	1.8 nM	US-9403767: Substituted 4-aminocyclohexane derivatives
benzimidazole analogue, 7i	EC50	1.8 nM
benzimidazole analogue, 7q	IC50	1.8 nM
1-[(1R,5S)-9-[(1S,6R)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-2-pyrrolidin-2-ylbenzimidazole	KI	1.9 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
8-((2-chloro-4-methylphenyl)(2-chlorophenyl)methyl)-3-cyclopentyl-8-azabicyclo[3.2.1]octan-3-ol	KI	1.9 nM
2-Cyclohexylcarbonylbenzimidazole, 7b	IC50	2 nM
exo-8-[Bis(2-chlorophenyl)methyl]-3-(2-piperidinyl)-8-azabicyclo[3.2.1]octane	KI	2 nM
(3R)-3-[[1-[(1S,5R)-9-[(1R,6S)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzimidazol-2-yl]methyl]morpholine	KI	2.05 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
benzimidazole analogue, 7d	EC50	2.1 nM
1-[(1R,5S)-9-[(1S,6R)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-2-(1H-1,2,4-triazol-5-yl)benzimidazole	KI	2.2 nM	US-9598411: Substituted benzimidazole-type piperidine compounds and uses thereof
4-[(1R,5S)-9-(3-bicyclo[3.3.1]nonanyl)-9-azabicyclo[3.3.1]nonan-3-yl]-3-oxoquinoxaline-2-carboxylic acid	KI	2.4 nM	US-8476271: Substituted-quinoxaline-type bridged-piperidine compounds as ORL-1 modulators
3-[(E)-2-diethoxyphosphorylethenyl]-1-[(1R,5S)-9-[(1S,5R)-7-methyl-3-bicyclo[3.3.1]nonanyl]-9-azabicyclo[3.3.1]nonan-3-yl]quinoxalin-2-one	KI	2.62 nM	US-9598447: Phosphorus-substituted quinoxaline-type piperidine compounds and uses thereof
[1-[(1S,5R)-9-[(1R,5S)-3-bicyclo[3.3.1]nonanyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzimidazol-2-yl]methanol	KI	2.68 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
8-((2-chloro-4-methylphenyl)(2-chlorophenyl)methyl)-3-(3-fluorophenyl)-8-azabicyclo[3.2.1]octan-3-ol	KI	2.7 nM
benzimidazole analogue, 5a	EC50	2.9 nM
2-[[4-[(1S,5R)-9-[(1R,5S)-7-methyl-3-bicyclo[3.3.1]nonanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3-oxoquinoxalin-2-yl]amino]ethylphosphonic acid	KI	2.92 nM	US-9598447: Phosphorus-substituted quinoxaline-type piperidine compounds and uses thereof
8-((2-chloro-4-methylphenyl)(2-chlorophenyl)methyl)-3-(1,4,5,6-tetrahydropyrimidin-2-yl)-8-azabicyclo[3.2.1]octan-3-ol	KI	3 nM
2-[4-[(1R,5S)-9-[(1S,5R)-7-methyl-3-bicyclo[3.3.1]nonanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3-oxoquinoxalin-2-yl]ethylphosphonic acid	KI	3.4 nM	US-9598447: Phosphorus-substituted quinoxaline-type piperidine compounds and uses thereof

ChEMBL bioactivities

3522 potent at pChembl≥5 of 3537 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	EC50	0.01	nM	NOCICEPTIN
10.70	Ki	0.01995	nM	CHEMBL442297
10.70	Ki	0.02	nM	CHEMBL415845
10.66	Ki	0.02188	nM	CHEMBL264846
10.60	Ki	0.02512	nM	CHEMBL411649
10.60	EC50	0.02512	nM	CHEMBL481366
10.55	Ki	0.02818	nM	CHEMBL409969
10.55	EC50	0.02818	nM	CHEMBL409969
10.52	Ki	0.03	nM	NALTRINDOLE
10.50	Ki	0.03162	nM	CHEMBL262544
10.48	IC50	0.033	nM	CHEMBL3343947
10.43	Ki	0.0373	nM	CHEMBL2088054
10.40	Ki	0.04	nM	CHEMBL3810319
10.33	IC50	0.0464	nM	CHEMBL414736
10.32	Ki	0.04786	nM	CHEMBL263588
10.31	Ki	0.04898	nM	NOCICEPTIN
10.30	Ki	0.05	nM	CHEMBL3808650
10.30	Ki	0.05	nM	CHEMBL266191
10.30	Ki	0.05	nM	CHEMBL414542
10.26	Ki	0.05495	nM	CHEMBL2372052
10.23	IC50	0.059	nM	CHEMBL3343949
10.22	Ki	0.06	nM	NOCICEPTIN
10.22	Ki	0.06	nM	CHEMBL438537
10.22	EC50	0.06	nM	CHEMBL414542
10.19	Ki	0.0648	nM	CHEMBL3236476
10.18	EC50	0.06607	nM	CHEMBL264846
10.17	Ki	0.0672	nM	CHEMBL2088061
10.17	EC50	0.06761	nM	CHEMBL414782
10.15	Ki	0.0711	nM	CHEMBL3236474
10.12	EC50	0.07586	nM	CHEMBL414782
10.10	IC50	0.0803	nM	CHEMBL441930
10.10	EC50	0.08	nM	NOCICEPTIN
10.10	Ki	0.08	nM	NOCICEPTIN
10.10	EC50	0.08	nM	CHEMBL266191
10.10	Ki	0.08	nM	CHEMBL408356
10.08	IC50	0.084	nM	NOCICEPTIN
10.07	Ki	0.0858	nM	CHEMBL481512
10.06	EC50	0.0871	nM	CHEMBL4781235
10.05	Ki	0.0892	nM	CHEMBL2088055
10.05	Ki	0.09	nM	CHEMBL2204347
10.05	EC50	0.09	nM	NOCICEPTIN
10.04	Ki	0.0902	nM	CHEMBL2088058
10.04	Ki	0.0908	nM	CHEMBL3236478
10.04	Ki	0.0916	nM	CHEMBL3236486
10.04	Kd	0.092	nM	NOCICEPTIN
10.03	Ki	0.0939	nM	CHEMBL3236479
10.02	Ki	0.0954	nM	CHEMBL3236475
10.01	Ki	0.097	nM	CHEMBL3236485
10.00	Ki	0.101	nM	CHEMBL2204353
10.00	EC50	0.1	nM	CHEMBL410653

PubChem BioAssay actives

2359 with measured affinity, of 3965 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
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-(diaminomethylideneamino)pentanamide	1302045: Displacement of [3H]OFQ/nociceptin from human nociceptin receptor expressed in CHO cell membrane incubated for 60 mins by liquid scintillation counting method	ki	<0.0001	uM
1-[2-(3-chlorophenyl)ethyl]-3-[2-(dimethylamino)-2-(3-fluorophenyl)ethyl]urea	2135043: Agonist activity at human NOP receptor expressed in CHO-K1 cells co-expressed with Galphai by cAMP assay	ec50	<0.0001	uM
1-[2-(dimethylamino)-2-(3-fluorophenyl)ethyl]-3-[(4-fluorophenyl)methyl]urea	2135043: Agonist activity at human NOP receptor expressed in CHO-K1 cells co-expressed with Galphai by cAMP assay	ec50	<0.0001	uM
(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoic acid	1820172: Displacement of [3H]nociceptin from human recombinant NOP receptor expressed in HEK293 cells by scintillation counting analysis	ki	<0.0001	uM
1-[2-(dimethylamino)-2-(3-fluorophenyl)ethyl]-3-[2-(3-methylphenyl)ethyl]urea	2135043: Agonist activity at human NOP receptor expressed in CHO-K1 cells co-expressed with Galphai by cAMP assay	ec50	<0.0001	uM
(2S)-6-amino-2-[[(2S,3S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-(3-methylbutanoylamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]pentanoyl]amino]-3-methylpentanoyl]amino]hexanamide	1167704: Displacement of [3H]]nociceptin from human ORL1 receptor high affinity binding site expressed in African green monkey COS7 cells after 90 mins by topcount analysis	ic50	<0.0001	uM
1-[1-(1-methylcyclooctyl)piperidin-4-yl]-2-[(3S)-piperidin-3-yl]benzimidazole	1573421: Agonist activity at human NOPR expressed in human BHK cells assessed as inhibition of forskolin-mediated cAMP accumulation after 10 mins by radioimmuno assay	ec50	<0.0001	uM
(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]pentanediamide	148870: Affinity for human Opioid receptor like 1 (ORL-1) expressed in HEK293 cells	ki	<0.0001	uM
(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-(4-fluorophenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]pentanediamide	239982: Receptor binding affinity for recombinant human N/OFQ peptide receptor (NOP) expressed in chinese hamster ovary cells	ki	<0.0001	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-N-[(2S)-5-(diaminoamino)-1-hydrazinyl-1,5-dioxopentan-2-yl]butanediamide	239982: Receptor binding affinity for recombinant human N/OFQ peptide receptor (NOP) expressed in chinese hamster ovary cells	ki	<0.0001	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-(4-fluorophenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-N-[(2S)-5-(diaminoamino)-1-hydrazinyl-1,5-dioxopentan-2-yl]butanediamide	239982: Receptor binding affinity for recombinant human N/OFQ peptide receptor (NOP) expressed in chinese hamster ovary cells	ki	<0.0001	uM
(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropyl]amino]acetyl]amino]acetyl]amino]-3-(4-fluorophenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]pentanediamide	239982: Receptor binding affinity for recombinant human N/OFQ peptide receptor (NOP) expressed in chinese hamster ovary cells	ki	<0.0001	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-N-[(2S)-5-(diaminoamino)-1-hydrazinyl-1,5-dioxopentan-2-yl]butanediamide	239982: Receptor binding affinity for recombinant human N/OFQ peptide receptor (NOP) expressed in chinese hamster ovary cells	ki	<0.0001	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropyl]amino]acetyl]amino]acetyl]amino]-3-(4-fluorophenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-N-[(2S)-5-(diaminoamino)-1-hydrazinyl-1,5-dioxopentan-2-yl]butanediamide	239982: Receptor binding affinity for recombinant human N/OFQ peptide receptor (NOP) expressed in chinese hamster ovary cells	ki	<0.0001	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[2-(benzylamino)acetyl]amino]acetyl]amino]acetyl]amino]-3-(4-fluorophenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-N-[(2S)-5-(diaminoamino)-1-hydrazinyl-1,5-dioxopentan-2-yl]butanediamide	239982: Receptor binding affinity for recombinant human N/OFQ peptide receptor (NOP) expressed in chinese hamster ovary cells	ki	<0.0001	uM
(2S)-N-[(2S)-1-[[2-[[2-[[(5S)-5-[[2-[[2-[[2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]-6-aminohexanoyl]amino]acetyl]amino]acetyl]amino]acetyl]amino]-6-amino-6-oxohexyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-3-hydroxy-1-oxopropan-2-yl]-1-[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carboxamide	271065: Displacement of [3H]NOC from human ORL1 receptor expressed in HEK293 cells	ic50	<0.0001	uM
(2S)-2-[[(2S)-4-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-(4-fluorophenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]-2-methylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-oxobutanoyl]amino]pentanediamide	296542: Displacement of [3H]N/OFQ from human recombinant NOP receptor expressed in CHO cells	ki	<0.0001	uM
(1S,2S,13R,21R)-22-(cyclopropylmethyl)-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5,7,9,15,17,19(25)-heptaene-2,16-diol	147935: Binding affinity against delta-opioid receptor in guinea pig brain membranes	ki	<0.0001	uM
2-[(2-chlorophenyl)methyl]-3-(2-chlorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4’-piperidine]-1’-yl)propanamide	682542: Displacement of [3H]Nociceptin from human recombinant NOP receptor expressed in CHO cells by scintillation counter	ki	<0.0001	uM
1-[2-(dimethylamino)-2-(3-fluorophenyl)ethyl]-3-[(3-fluorophenyl)methyl]urea	2135043: Agonist activity at human NOP receptor expressed in CHO-K1 cells co-expressed with Galphai by cAMP assay	ec50	<0.0001	uM
(2S)-6-amino-2-[[(2S,3S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-(2-methylpropanoylamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]pentanoyl]amino]-3-methylpentanoyl]amino]hexanamide	1167704: Displacement of [3H]]nociceptin from human ORL1 receptor high affinity binding site expressed in African green monkey COS7 cells after 90 mins by topcount analysis	ic50	0.0001	uM
(2R)-1-benzyl-N-(3-spiro[1H-2-benzofuran-3,4’-piperidine]-1’-ylpropyl)pyrrolidine-2-carboxamide	259848: Antagonist activity on nociceptin-induced [35S]GTP-gamma-S binding to ORL1 expressed in CHO cells	ic50	0.0001	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-fluorophenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-(diaminomethylideneamino)pentanamide	1302045: Displacement of [3H]OFQ/nociceptin from human nociceptin receptor expressed in CHO cell membrane incubated for 60 mins by liquid scintillation counting method	ki	0.0001	uM
(2R)-1-benzyl-N-(3-spiro[1,2-dihydroindene-3,4’-piperidine]-1’-ylpropyl)pyrrolidine-2-carboxamide	259848: Antagonist activity on nociceptin-induced [35S]GTP-gamma-S binding to ORL1 expressed in CHO cells	ic50	0.0001	uM
(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[4-[3-[(2R)-3-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-3-oxopropyl]sulfanyl-2,5-dioxopyrrolidin-1-yl]butanoylamino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanoyl]amino]hexanamide	1676249: Agonist activity at NOP (unknown origin) expressed in HEK293 cell membranes co-expressing Gbeta1-RGFP protein assessed as induction of G protein activation incubated for 15 mins by BRET assay	ec50	0.0001	uM
1-[1-(1-methylcyclooctyl)piperidin-4-yl]-2-[(3R)-piperidin-3-yl]benzimidazole	367833: Displacement of [3H]N/OFQ from human NOP receptor expressed in HEK293 cells	ki	0.0001	uM
(2R)-1-benzyl-N-[3-[4-(2,6-dichlorophenyl)piperidin-1-yl]propyl]pyrrolidine-2-carboxamide	600426: Antagonist activity at human recombinant NOP expressed in CHO cells by [35S]GTPgammaS binding assay	kd	0.0001	uM
(4R,7S,10S,13S,16R)-16-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-7-(4-aminobutyl)-10-[3-(diaminomethylideneamino)propyl]-13-methyl-6,9,12,15-tetraoxo-1,2-dithia-5,8,11,14-tetrazacycloheptadecane-4-carboxamide	147768: Displacement of [3H]NC from human ORL1 receptor expressing HEK293 cell membrane	ic50	0.0001	uM
(4R,7S,10S,13R)-7-(4-aminobutyl)-13-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]-10-[3-(diaminomethylideneamino)propyl]-6,9,12-trioxo-1,2-dithia-5,8,11-triazacyclotetradecane-4-carboxamide	342867: Binding affinity to human NOP receptor	ki	0.0001	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-(4-nitrophenyl)propanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanamide	147636: Inhibition of forskolin stimulated cAMP accumulation in CHO cells stably expressing the human OP4 receptor	ec50	0.0001	uM
1-[1-(1-methylcyclooctyl)piperidin-4-yl]-2-(3-methylsulfonylphenyl)benzimidazole	367833: Displacement of [3H]N/OFQ from human NOP receptor expressed in HEK293 cells	ki	0.0001	uM
(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]pentanediamide	239982: Receptor binding affinity for recombinant human N/OFQ peptide receptor (NOP) expressed in chinese hamster ovary cells	ki	0.0001	uM
(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoic acid	1798132: Radioligand Binding Assay from Article 10.1021/jm7009606: “Synthesis and pharmacological evaluation of 1,2-dihydrospiro[isoquinoline-4(3H),4’-piperidin]-3-ones as nociceptin receptor agonists.”	ki	0.0001	uM
(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]-methylamino]propanoyl]amino]-4-oxobutanoyl]amino]pentanediamide	148870: Affinity for human Opioid receptor like 1 (ORL-1) expressed in HEK293 cells	ki	0.0001	uM
(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]butanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]butanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]pentanediamide	148859: Affinity for human Opioid receptor like 1 (ORL-1) expressed in HEK293 cells	ec50	0.0001	uM
(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]butanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoic acid	148870: Affinity for human Opioid receptor like 1 (ORL-1) expressed in HEK293 cells	ki	0.0001	uM
(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]butanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoic acid	148870: Affinity for human Opioid receptor like 1 (ORL-1) expressed in HEK293 cells	ki	0.0001	uM
(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]butanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]pentanediamide	148859: Affinity for human Opioid receptor like 1 (ORL-1) expressed in HEK293 cells	ec50	0.0001	uM
(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]butanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]pentanediamide	148859: Affinity for human Opioid receptor like 1 (ORL-1) expressed in HEK293 cells	ec50	0.0001	uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[(2S)-2-[[2-[[2-[[2-(benzylamino)acetyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanoyl]amino]-N-[(2S)-5-(diaminoamino)-1-hydrazinyl-1,5-dioxopentan-2-yl]butanediamide	239982: Receptor binding affinity for recombinant human N/OFQ peptide receptor (NOP) expressed in chinese hamster ovary cells	ki	0.0001	uM
(2S)-6-amino-N-[2-[[2-[[2-[[(2S)-1-amino-6-[[2-[[2-[3-[[(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]propanoylamino]acetyl]amino]acetyl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-2-oxoethyl]-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylpentanoyl]amino]hexanamide	271065: Displacement of [3H]NOC from human ORL1 receptor expressed in HEK293 cells	ic50	0.0001	uM
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]-3,4-dichlorobenzamide;oxalic acid	450065: Inverse agonist activity at NOP expressed in HEK293 cells assessed as inhibition of [35S]GTPgammaS binding	ec50	0.0001	uM
(2S)-2-[(2-chlorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4’-piperidine]-1’-yl)propanamide	712467: Displacement of [3H]nociceptin from human recombinant NOP receptor expressed in CHO cells after 60 mins by microbeta scintillation counting	ki	0.0001	uM
(2S)-2-[(2-fluorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4’-piperidine]-1’-yl)propanamide	682542: Displacement of [3H]Nociceptin from human recombinant NOP receptor expressed in CHO cells by scintillation counter	ki	0.0001	uM
(2S)-2-[(2-fluorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4’-piperidine]-1’-yl)-N-methyl-N-propan-2-ylpropanamide	682542: Displacement of [3H]Nociceptin from human recombinant NOP receptor expressed in CHO cells by scintillation counter	ki	0.0001	uM
(2S)-2-[(2-chlorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4’-piperidine]-1’-yl)-N-methylpropanamide	712467: Displacement of [3H]nociceptin from human recombinant NOP receptor expressed in CHO cells after 60 mins by microbeta scintillation counting	ki	0.0001	uM
(2S)-2-[(2-fluorophenyl)methyl]-3-(2-fluorospiro[4,5-dihydrothieno[2,3-c]pyran-7,4’-piperidine]-1’-yl)-N-methylpropanamide	712467: Displacement of [3H]nociceptin from human recombinant NOP receptor expressed in CHO cells after 60 mins by microbeta scintillation counting	ki	0.0001	uM
[1-[4-[2-(4-chlorophenyl)benzimidazol-1-yl]piperidin-1-yl]cyclooctyl]methanol	565967: Displacement of [3H]N/OFQ from human NOP receptor expressed in HEK293 cells after 45 mins	ki	0.0001	uM
2-chloro-4,4-difluoro-1’-[[1-[3-(1H-imidazol-2-yl)-2-pyridinyl]-3-methylpyrazol-4-yl]methyl]spiro[5H-thieno[2,3-c]pyran-7,4’-piperidine]	1126451: Displacement of [3H]-nociceptin from human recombinant NOP receptor expressed in CHO cells after 60 mins by scintillation counting	ki	0.0001	uM
N,N-dimethyl-1’-phenylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4’-cyclohexane]-1’-amine;hydrochloride	1188847: Displacement of [3H]nociceptin from human NOP receptor expressed in CHO-K1 cells by scintillation proximity assay	ki	0.0001	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nociceptin	affects binding, decreases reaction, increases activity	2
Benzo(a)pyrene	affects methylation	2
Cisplatin	affects expression, affects cotreatment, increases expression	2
Estradiol	affects binding, increases expression, decreases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
beta-lapachone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
tebuconazole	decreases expression	1
AM 251	decreases expression, decreases reaction	1
2-palmitoylglycerol	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
cis-1-methyl-7-((4-(2,6-dichlorophenyl)piperidin-1-yl)methyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol	affects activity, affects binding	1
jinfukang	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Buprenorphine	affects binding, increases activity	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, decreases expression	1
Silicon Dioxide	decreases expression	1
Dronabinol	decreases expression, decreases reaction	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
S-Nitrosoglutathione	increases expression	1
Endocannabinoids	affects binding, decreases reaction, increases activity	1

ChEMBL screening assays

430 unique, capped per target: 249 binding, 181 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000195	Binding	Binding affinity to ORL1 receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1001568	Functional	Antagonist activity at human recombinant NOP receptor expressed in CHO cells coexpressing alphaqi5 assessed as inhibition of N/OFQ-induced intracellular calcium mobilization	Further studies at neuropeptide s position 5: discovery of novel neuropeptide S receptor antagonists. — J Med Chem

Cellosaurus cell lines

8 cell lines: 4 spontaneously immortalized cell line, 2 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0TD	ACTOne OPRL1	Transformed cell line	Female
CVCL_H485	CHO-K1/OPRL1/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KV61	cAMP Hunter CHO-K1 OPRL1 Gi	Spontaneously immortalized cell line	Female
CVCL_KY69	PathHunter CHO-K1 OPRL1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA99	PathHunter U2OS OPRL1 Total GPCR Internalization	Cancer cell line	Female
CVCL_U008	CHO-OPRL1	Spontaneously immortalized cell line	Female
CVCL_XA26	GeneBLAzer OPRL1-Gqi5-NFAT-bla FreeStyle 293F	Transformed cell line	Female
CVCL_ZL08	Tango OPRL1-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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