OGFRL1

Summary

OGFRL1 (opioid growth factor receptor like 1, HGNC:21378) is a protein-coding gene on chromosome 6q13, encoding Opioid growth factor receptor-like protein 1 (Q5TC84).

Predicted to enable opioid growth factor receptor activity. Predicted to be located in membrane.

Source: NCBI Gene 79627 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 50 total
• Druggable target: yes
• MANE Select transcript: NM_024576

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21378
Approved symbol	OGFRL1
Name	opioid growth factor receptor like 1
Location	6q13
Locus type	gene with protein product
Status	Approved
Aliases	dJ331H24.1
Ensembl gene	ENSG00000119900
Ensembl biotype	protein_coding
OMIM	621133
Entrez	79627

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000370435, ENST00000467503, ENST00000650315

RefSeq mRNA: 2 — MANE Select: NM_024576 NM_001324266, NM_024576

CCDS: CCDS34482

Canonical transcript exons

ENST00000370435 — 7 exons

Exon	Start	End
ENSE00000810385	71296672	71296817
ENSE00001026823	71296495	71296561
ENSE00001150522	71296317	71296395
ENSE00001203095	71293533	71293611
ENSE00001452720	71301386	71309059
ENSE00001452724	71288811	71289170
ENSE00003586652	71293293	71293379

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.4149 / max 988.9540, expressed in 1739 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68491	27.9373	1715
68488	2.9741	925
68490	1.7591	822
68492	1.2349	736
68489	0.8670	366
68494	0.3270	154
68495	0.3155	122

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior vestibular nucleus	UBERON:0007227	99.07	gold quality
pons	UBERON:0000988	99.01	gold quality
upper leg skin	UBERON:0004262	98.81	gold quality
subthalamic nucleus	UBERON:0001906	98.78	gold quality
lateral globus pallidus	UBERON:0002476	98.68	gold quality
skin of hip	UBERON:0001554	98.54	gold quality
endothelial cell	CL:0000115	98.52	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.51	gold quality
substantia nigra pars compacta	UBERON:0001965	98.42	gold quality
parietal pleura	UBERON:0002400	98.38	gold quality
epithelium of nasopharynx	UBERON:0001951	98.19	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.12	gold quality
oral cavity	UBERON:0000167	97.76	gold quality
mammary duct	UBERON:0001765	97.59	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.56	gold quality
penis	UBERON:0000989	97.49	gold quality
inferior vagus X ganglion	UBERON:0005363	97.49	gold quality
parotid gland	UBERON:0001831	97.44	gold quality
monocyte	CL:0000576	97.41	gold quality
esophagus squamous epithelium	UBERON:0006920	97.40	gold quality
mononuclear cell	CL:0000842	97.36	gold quality
leukocyte	CL:0000738	97.08	gold quality
globus pallidus	UBERON:0001875	97.03	gold quality
entorhinal cortex	UBERON:0002728	96.83	gold quality
ventral tegmental area	UBERON:0002691	96.82	gold quality
medial globus pallidus	UBERON:0002477	96.65	gold quality
trabecular bone tissue	UBERON:0002483	96.40	gold quality
pleura	UBERON:0000977	96.35	gold quality
mammalian vulva	UBERON:0000997	96.33	gold quality
gingival epithelium	UBERON:0001949	96.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

257 targeting OGFRL1, 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-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ogfrl1	ENSDARG00000061223
mus_musculus	Ogfrl1	ENSMUSG00000026158
rattus_norvegicus	Ogfrl1	ENSRNOG00000014142

Paralogs (1): OGFR (ENSG00000060491)

Protein

Protein identifiers

Opioid growth factor receptor-like protein 1 — Q5TC84 (reviewed: Q5TC84)

All UniProt accessions (2): Q5TC84, A0A3B3IRI0

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Ubiquitous.

Similarity. Belongs to the opioid growth factor receptor family.

RefSeq proteins (2): NP_001311195, NP_078852* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006757	OGF_rcpt	Domain
IPR039574	OGFr	Family

Pfam: PF04664

UniProt features (10 total): compositionally biased region 5, region of interest 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TC84-F1	73.11	0.53

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 237 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, FOSTER_TOLERANT_MACROPHAGE_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, COATES_MACROPHAGE_M1_VS_M2_UP, WANG_TARGETS_OF_MLL_CBP_FUSION_UP, GOMF_PEPTIDE_RECEPTOR_ACTIVITY, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, SENESE_HDAC1_TARGETS_UP, RIGGINS_TAMOXIFEN_RESISTANCE_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GEORGES_TARGETS_OF_MIR192_AND_MIR215, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_UP

GO Biological Process (0):

GO Molecular Function (2): opioid growth factor receptor activity (GO:0140625), signaling receptor activity (GO:0038023)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptide receptor activity	1
molecular transducer activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OGFRL1	UBTD2	Q8WUN7	396
OGFRL1	CIBAR1	A1XBS5	374
OGFRL1	C2CD2	Q9Y426	368
OGFRL1	DNAAF8	Q8IYS4	349
OGFRL1	OPRD1	P41143	344
OGFRL1	CCDC150	Q8NCX0	328
OGFRL1	C3orf52	Q5BVD1	323
OGFRL1	TRDMT1	O14717	318
OGFRL1	OSGIN1	Q9UJX0	315
OGFRL1	TM2D1	Q9BX74	314
OGFRL1	ZNF502	Q8TBZ5	310
OGFRL1	ZNF345	Q14585	310
OGFRL1	MROH6	A6NGR9	306
OGFRL1	ZNF729	A6NN14	305
OGFRL1	ZNF845	Q96IR2	305

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CDK4	HSP90AA1	psi-mi:“MI:0914”(association)	0.640
CDK4	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
SELENBP1	ZNF24	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): OGFRL1 (Affinity Capture-MS), OGFRL1 (Affinity Capture-MS), OGFRL1 (Affinity Capture-MS), OGFRL1 (Affinity Capture-MS), OGFRL1 (Cross-Linking-MS (XL-MS)), OGFRL1 (Proximity Label-MS), OGFRL1 (Proximity Label-MS), OGFRL1 (Proximity Label-MS), OGFRL1 (Proximity Label-MS)

ESM2 similar proteins: A0A0R4IBK5, A0JP43, A1A5R8, A2VCV0, B8QB46, P62283, P62285, P62286, P62287, P62288, P62289, P62290, P62291, P62292, P62293, P62294, P62296, P62297, Q06190, Q08AX9, Q12830, Q2T9I9, Q4KLH3, Q4VA55, Q5RA75, Q5TC84, Q5ZMS4, Q65Z40, Q66H73, Q68FF0, Q6DFV7, Q6NSI8, Q6PG04, Q6PUR7, Q6TXG9, Q7T3T8, Q7Z5K2, Q8CJ27, Q8IZT6, Q8K4P8

Diamond homologs: A2VCV0, Q4KLH3, Q5TC84, Q8VE52, Q99PG2, Q9NZT2, Q9QXY4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

962 predictions. Top by Δscore:

Variant	Effect	Δscore
6:71293287:TTTCA:T	acceptor_loss	1.0000
6:71293288:TTCA:T	acceptor_loss	1.0000
6:71293289:TCAG:T	acceptor_loss	1.0000
6:71293290:CAG:C	acceptor_loss	1.0000
6:71293291:A:AG	acceptor_gain	1.0000
6:71293291:A:C	acceptor_loss	1.0000
6:71293291:AG:A	acceptor_gain	1.0000
6:71293291:AGGGT:A	acceptor_gain	1.0000
6:71293292:G:GG	acceptor_gain	1.0000
6:71293292:G:GT	acceptor_loss	1.0000
6:71293292:GG:G	acceptor_gain	1.0000
6:71293292:GGGT:G	acceptor_gain	1.0000
6:71293292:GGGTG:G	acceptor_gain	1.0000
6:71293375:ACCC:A	donor_gain	1.0000
6:71293380:G:GG	donor_gain	1.0000
6:71293384:GA:G	donor_gain	1.0000
6:71293386:G:GG	donor_gain	1.0000
6:71293396:C:G	donor_gain	1.0000
6:71293529:GCA:G	acceptor_gain	1.0000
6:71293608:GATG:G	donor_gain	1.0000
6:71293609:ATGG:A	donor_loss	1.0000
6:71293610:TGGTG:T	donor_loss	1.0000
6:71293612:G:C	donor_loss	1.0000
6:71293612:G:GG	donor_gain	1.0000
6:71293613:T:A	donor_loss	1.0000
6:71293614:G:GT	donor_loss	1.0000
6:71293615:AGT:A	donor_loss	1.0000
6:71293616:G:GG	donor_gain	1.0000
6:71296313:TTA:T	acceptor_loss	1.0000
6:71296314:TA:T	acceptor_loss	1.0000

AlphaMissense

3003 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:71289003:T:A	W23R	1.000
6:71289003:T:C	W23R	1.000
6:71289005:G:C	W23C	1.000
6:71289005:G:T	W23C	1.000
6:71293331:A:C	R91S	1.000
6:71293331:A:T	R91S	1.000
6:71293332:A:C	S92R	1.000
6:71293334:T:A	S92R	1.000
6:71293334:T:G	S92R	1.000
6:71293342:C:A	A95D	1.000
6:71293345:C:A	A96D	1.000
6:71293350:G:C	D98H	1.000
6:71293351:A:C	D98A	1.000
6:71293351:A:G	D98G	1.000
6:71293351:A:T	D98V	1.000
6:71293352:T:A	D98E	1.000
6:71293352:T:G	D98E	1.000
6:71293354:T:G	L99W	1.000
6:71293362:T:C	Y102H	1.000
6:71293362:T:G	Y102D	1.000
6:71293363:A:C	Y102S	1.000
6:71293363:A:G	Y102C	1.000
6:71293365:C:G	R103G	1.000
6:71293366:G:C	R103P	1.000
6:71293374:T:C	Y106H	1.000
6:71293571:T:A	N120K	1.000
6:71293571:T:G	N120K	1.000
6:71293573:T:C	L121P	1.000
6:71293578:T:C	F123L	1.000
6:71293579:T:C	F123S	1.000

dbSNP variants (sampled 300 via entrez): RS1000014324 (6:71300076 A>G), RS1000074607 (6:71290265 C>G), RS1000136343 (6:71309403 A>G), RS1000385780 (6:71302210 T>C), RS1000445264 (6:71294548 G>C), RS1000600740 (6:71288030 C>T), RS1000728429 (6:71295707 G>A), RS1001119313 (6:71287576 A>C), RS1001161411 (6:71294881 T>C), RS1001213528 (6:71289097 C>A,T), RS1001482260 (6:71303011 G>A), RS1001575614 (6:71303370 T>A), RS1001826997 (6:71287105 T>C,G), RS1001888398 (6:71302588 C>T), RS1001911124 (6:71301857 T>G)

Disease associations

OMIM: gene MIM:621133 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003108_1	Antipsychotic drug-induced weight gain (time interaction)	6.000000e-06
GCST003109_1	Antipsychotic drug-induced weight gain	1.000000e-07
GCST006627_49	Diastolic blood pressure	3.000000e-11
GCST007576_239	Chronotype	5.000000e-11
GCST010002_326	Refractive error	3.000000e-205

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004567	antipsychotic drug related weight gain
EFO:0005937	longitudinal BMI measurement
EFO:0006336	diastolic blood pressure
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3638334 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

395 measured of 439 human assays (439 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S,6R)-11,15-dimethoxy-5-methyl-16-(phenylmethoxymethyl)-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	KI	0.17 nM	US-8530494: Buprenophine analogs
N,N-dimethyl-1’-phenylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	0.36 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
N,N,3-trimethyl-1’-phenylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	0.5 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
(1S,10R,11R)-N-[(2S)-1-amino-1-oxopropan-2-yl]-21-(cyclopropylmethyl)-16-hydroxy-5-oxo-4,21-diazapentacyclo[9.7.3.01,10.03,8.013,18]henicosa-3,6,13(18),14,16-pentaene-6-carboxamide	KI	0.56 nM	US-8980906: Pyridonemorphinan analogs and biological activity on opioid receptors
(1S,10R,11R)-N-(2-amino-2-oxoethyl)-21-(cyclopropylmethyl)-16-hydroxy-5-oxo-4,21-diazapentacyclo[9.7.3.01,10.03,8.013,18]henicosa-3,6,13(18),14,16-pentaene-6-carboxamide	KI	0.59 nM	US-8980906: Pyridonemorphinan analogs and biological activity on opioid receptors
N,N-dimethyl-1’-phenylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	0.6 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
1’-benzyl-N,N-dimethylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	0.6 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
6-fluoro-N,N-dimethyl-1’-phenylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	0.7 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
(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
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
1’-(dimethylamino)-1’-phenylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4’-cyclohexane]-6-ol	KI	1.1 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
4-[(1S,5R)-9-[(1R,5S)-7-methyl-3-bicyclo[3.3.1]nonanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3-oxoquinoxaline-2-carboxylate	KI	1.1 nM	US-9145408: 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-methyl-1’-phenylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	1.2 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
6-fluoro-N,N-dimethyl-1’-phenylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	1.5 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
1-[1’-(dimethylamino)-7-fluoro-1’-phenylspiro[4,9-dihydro-3H-pyrido[3,4-b]indole-1,4’-cyclohexane]-2-yl]ethanone	KI	1.7 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
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
6-methoxy-N,N-dimethyl-1’-phenylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	2 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
(2S)-2-amino-N-[[(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11-hydroxy-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-16-yl]methyl]-3-phenylpropanamide	KI	2.01 nM	US-8969358: Buprenorphine analogs
(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
1’-(3-fluorophenyl)-N,N-dimethylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	2.1 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
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
1-[1’-(dimethylamino)-1’-phenylspiro[4,9-dihydro-3H-pyrido[3,4-b]indole-1,4’-cyclohexane]-2-yl]ethanone	KI	2.2 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
methyl 1’-(dimethylamino)-1’-phenylspiro[2,3,4,9-tetrahydropyrido[3,4-b]indole-1,4’-cyclohexane]-3-carboxylate	KI	2.3 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
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
[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
N,N,6-trimethyl-1’-phenylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	2.7 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
N,N-dimethyl-1’-phenylspiro[4,9-dihydro-3H-thiopyrano[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	3.1 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
1-[(1S,5R)-9-[(1R,6S)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-2-[(5-methyl-1H-1,2,4-triazol-3-yl)methyl]benzimidazole	KI	3.8 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
4-[(1R,5S)-8-(3,5-dimethyl-1-adamantyl)-8-azabicyclo[3.2.1]octan-3-yl]-3-oxoquinoxaline-2-carboxylic acid	KI	4.1 nM	US-8846929: Substituted-quinoxaline-type piperidine compounds and the uses thereof
1-[(1S,5R)-9-[(1S,5R)-3-bicyclo[3.3.1]nonanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-2-(5-methoxypyrazin-2-yl)benzimidazole	KI	4.11 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
3-[1-[(1R,5S)-9-[(1R,5S)-3-bicyclo[3.3.1]nonanyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzimidazol-2-yl]-5-methyl-1,2-oxazole	KI	4.2 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
2-[1-[4-[(1R,5S)-9-[(1S,6R)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3-oxoquinoxalin-2-yl]azetidin-3-yl]acetic acid	EC50	4.2 nM	US-9290488: Azetidine-substituted quinoxalines as opioid receptor like-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-ylmethyl)benzimidazole	KI	4.5 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
2-[3-[1-[(1S,5R)-9-[(1R,6S)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzimidazol-2-yl]azetidin-1-yl]acetic acid	KI	4.73 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
(3S)-3-[[1-[(1R,5S)-9-[(1S,6R)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzimidazol-2-yl]methyl]morpholine	KI	5.4 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
4-[(1R,5S)-8-(3-bicyclo[3.3.1]nonanyl)-8-azabicyclo[3.2.1]octan-3-yl]-3-oxoquinoxaline-2-carboxylic acid	KI	5.7 nM	US-8476271: Substituted-quinoxaline-type bridged-piperidine compounds as ORL-1 modulators
N-[2-[(3S)-3-[[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-1-yl]ethyl]methanesulfonamide	KI	6.14 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
1-[(1R,5S)-9-[(1S,6R)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]-2-(4-chloro-1-methylpyrazol-3-yl)benzimidazole	KI	6.7 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
6-fluoro-N-methyl-1’-phenylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	6.8 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
5-[1-[(1S,5R)-9-[(1S,5R)-3-bicyclo[3.3.1]nonanyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzimidazol-2-yl]-1,2-oxazole	KI	7.1 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
1’-(4-fluorophenyl)-N,N-dimethylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4’-cyclohexane]-1’-amine	KI	7.2 nM	US-9120797: Process for preparing spirocyclic cyclohexane compounds, compositions containing such compounds and method of using such compounds
(2S)-2-[[4-[(1R,5S)-8-cyclooctyl-8-azabicyclo[3.2.1]octan-3-yl]-3-oxoquinoxalin-2-yl]amino]-3-hydroxypropanoic acid	KI	8.2 nM	US-8846929: Substituted-quinoxaline-type piperidine compounds and the uses thereof
(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]-4-[(1-methylimidazol-2-yl)methyl]morpholine	KI	8.5 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
4-[(1R,5S)-9-(1-methylcyclooctyl)-9-azabicyclo[3.3.1]nonan-3-yl]-3-oxoquinoxaline-2-carboxylic acid	KI	8.6 nM	US-8846929: Substituted-quinoxaline-type piperidine compounds and the uses thereof
3-[3-[1-[(1S,5R)-9-[(1R,6S)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzimidazol-2-yl]azetidin-1-yl]propanoic acid	KI	8.9 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
2-[(2R)-2-[1-[(1R,5S)-9-[(1S,6R)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzimidazol-2-yl]pyrrolidin-1-yl]acetic acid	KI	9 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11,15-dimethoxy-16-(phenylmethoxymethyl)-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-triene	KI	9.2 nM	US-8530494: Buprenophine analogs
N-[2-[(3S)-3-[[1-[(1R,5S)-9-[(1S,6R)-8-bicyclo[4.3.1]decanyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzimidazol-2-yl]methyl]piperidin-1-yl]ethyl]methanesulfonamide	KI	11.5 nM	US-9090618: Substituted benzimidazole-type piperidine compounds and uses thereof
4-[(1R,5S)-8-(1-adamantyl)-8-azabicyclo[3.2.1]octan-3-yl]-3-oxoquinoxaline-2-carboxylic acid	KI	11.9 nM	US-8846929: Substituted-quinoxaline-type piperidine compounds and the uses thereof

ChEMBL bioactivities

485 potent at pChembl≥5 of 487 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.66	Ki	0.22	nM	CHEMBL3961680
9.59	Ki	0.26	nM	CHEMBL3894898
9.52	Ki	0.3	nM	CHEMBL3959398
9.47	Ki	0.34	nM	CHEMBL3969279
9.30	Ki	0.5	nM	CHEMBL3894557
9.26	EC50	0.55	nM	CHEMBL3647962
9.22	Ki	0.6	nM	CHEMBL3959398
9.10	Ki	0.8	nM	CHEMBL3704630
9.05	Ki	0.9	nM	CHEMBL3892859
9.05	Ki	0.89	nM	CHEMBL4115318
9.04	Ki	0.92	nM	CHEMBL3704619
8.99	Ki	1.03	nM	CHEMBL3903565
8.96	Ki	1.1	nM	CHEMBL3890825
8.96	Ki	1.1	nM	CHEMBL3966641
8.96	Ki	1.1	nM	CHEMBL3647962
8.94	Ki	1.15	nM	CHEMBL3704618
8.92	Ki	1.2	nM	CHEMBL4115767
8.92	Ki	1.2	nM	CHEMBL3909041
8.92	Ki	1.2	nM	CHEMBL3961861
8.91	EC50	1.24	nM	CHEMBL3903565
8.88	Ki	1.32	nM	CHEMBL3913056
8.85	Ki	1.4	nM	CHEMBL3698900
8.85	Ki	1.4	nM	CHEMBL3698827
8.85	Ki	1.4	nM	CHEMBL3953613
8.85	Ki	1.4	nM	CHEMBL3954763
8.84	Ki	1.46	nM	CHEMBL3935191
8.80	Ki	1.6	nM	CHEMBL3695221
8.80	Ki	1.6	nM	CHEMBL3959597
8.74	Ki	1.8	nM	CHEMBL3698899
8.72	Ki	1.9	nM	CHEMBL6067666
8.71	Ki	1.97	nM	CHEMBL4110144
8.70	Ki	2	nM	CHEMBL3698904
8.70	Ki	2	nM	CHEMBL3704616
8.70	Ki	1.98	nM	CHEMBL4107295
8.70	Ki	1.98	nM	CHEMBL4110576
8.69	Ki	2.04	nM	CHEMBL4115760
8.69	Ki	2.05	nM	CHEMBL3704632
8.66	Ki	2.21	nM	CHEMBL3986914
8.62	Ki	2.4	nM	CHEMBL3647958
8.62	Ki	2.4	nM	CHEMBL3919062
8.60	Ki	2.5	nM	CHEMBL3698902
8.58	Ki	2.64	nM	CHEMBL3973642
8.58	EC50	2.62	nM	CHEMBL4115318
8.57	Ki	2.7	nM	CHEMBL3695242
8.57	Ki	2.68	nM	CHEMBL3704613
8.55	Ki	2.8	nM	CHEMBL3698898
8.54	Ki	2.9	nM	CHEMBL3919062
8.54	Ki	2.9	nM	CHEMBL3962932
8.51	Ki	3.1	nM	CHEMBL3695235
8.51	Ki	3.07	nM	CHEMBL4107594

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases methylation	4
Estradiol	affects cotreatment, increases expression, decreases expression	3
Tretinoin	increases expression, decreases expression	3
methylmercuric chloride	decreases expression, increases expression	2
bisphenol A	decreases expression, increases methylation	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
trichostatin A	increases expression, decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
nickel chloride	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
potassium chromate(VI)	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
torcetrapib	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3705335	Binding	Binding Assay: Binding assay of certain compounds of this invention to the opioid receptor was determine using radioligand binding assay (screening and dose-displacement).	Buprenophine analogs

Clinical trials (associated diseases)

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