CHRNA6

Summary

CHRNA6 (cholinergic receptor nicotinic alpha 6 subunit, HGNC:15963) is a protein-coding gene on chromosome 8p11.21, encoding Neuronal acetylcholine receptor subunit alpha-6 (Q15825). Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate syna….

This gene encodes an alpha subunit of neuronal nicotinic acetylcholine receptors. These receptors consist of five subunits and function as ion channels involved in neurotransmission. The encoded protein is a subunit of neuronal nicotinic acetylcholine receptors that mediate dopaminergic neurotransmission and are activated by acetylcholine and exogenous nicotine. Alternatively spliced transcript variants have been observed for this gene. Single nucleotide polymorphisms in this gene have been associated with both nicotine and alcohol dependence.

Source: NCBI Gene 8973 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 64 total — 2 pathogenic, 2 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004198

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15963
Approved symbol	CHRNA6
Name	cholinergic receptor nicotinic alpha 6 subunit
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000147434
Ensembl biotype	protein_coding
OMIM	606888
Entrez	8973

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000276410, ENST00000529467, ENST00000530869, ENST00000533810, ENST00000534622

RefSeq mRNA: 2 — MANE Select: NM_004198 NM_001199279, NM_004198

CCDS: CCDS56536, CCDS6135

Canonical transcript exons

ENST00000276410 — 6 exons

Exon	Start	End
ENSE00000980082	42756928	42757037
ENSE00000980083	42755846	42756824
ENSE00001041949	42752620	42753310
ENSE00002169398	42768352	42768786
ENSE00003536415	42765065	42765204
ENSE00003663076	42759069	42759113

Expression profiles

Bgee: expression breadth broad, 80 present calls, max score 76.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0960 / max 25.1535, expressed in 47 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92922	0.0235	11
92923	0.0214	6
92926	0.0181	8
92928	0.0107	3
92924	0.0106	3
92925	0.0073	4
92927	0.0043	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	76.51	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.60	gold quality
buccal mucosa cell	CL:0002336	68.62	gold quality
orbitofrontal cortex	UBERON:0004167	67.79	gold quality
tibialis anterior	UBERON:0001385	66.90	silver quality
ileal mucosa	UBERON:0000331	64.47	gold quality
Brodmann (1909) area 10	UBERON:0013541	59.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.70	gold quality
substantia nigra pars reticulata	UBERON:0001966	59.29	gold quality
cerebellar cortex	UBERON:0002129	57.98	gold quality
cerebellum	UBERON:0002037	57.78	gold quality
deltoid	UBERON:0001476	57.76	silver quality
cerebellar hemisphere	UBERON:0002245	57.66	gold quality
cerebellar vermis	UBERON:0004720	57.09	gold quality
triceps brachii	UBERON:0001509	56.78	gold quality
decidua	UBERON:0002450	56.55	gold quality
prefrontal cortex	UBERON:0000451	55.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	54.68	gold quality
endometrium epithelium	UBERON:0004811	54.33	gold quality
epithelial cell of pancreas	CL:0000083	54.06	gold quality
substantia nigra	UBERON:0002038	53.54	gold quality
lateral globus pallidus	UBERON:0002476	53.34	gold quality
substantia nigra pars compacta	UBERON:0001965	52.98	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
midbrain	UBERON:0001891	52.11	gold quality
quadriceps femoris	UBERON:0001377	51.58	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
tibia	UBERON:0000979	50.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

35 targeting CHRNA6, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-6804-5P	98.39	65.77	1084

Literature-anchored findings (GeneRIF, showing 29)

• CHRNA6 is associated with subjective responses to tobacco. (PMID:18055561)
• Together these results further implicate the region downstream of CHRNA6 and the region upstream of CHRNB3 in risk of nicotine dependence. (PMID:18704094)
• Alpha6 subunit-containing nicotinic receptors play a selective role in the modulation of dopamine release in both the nucleus accumbens and in the dorsal striatum. (PMID:18940582)
• Activating transgenic gain-of-function alpha 6 nicotinic receptors in dopamine neurons is sufficient to cause locomotor hyperactivity. (PMID:18940593)
• Three single nucleotide polymorphisms (SNPs) in CHRNA6 and one SNP in CHRNB3 are associated with a composite of alcohol phenotypes. (PMID:19500157)
• present findings disclose a haplotype association between the CHRNA6 gene and heavy alcohol use as well as an association of the CHRNA4 gene with increased body mass in heavy consumers of alcohol (PMID:19698703)
• The negative consequences of Prenatal exposure to maternal cigarette smoking on the brain and behavior of adolescence and suggestion that the alpha6 nAChR subunit may modify, at least in part, these effects. (PMID:20029407)
• CHRNB3-CHRNA6 and CYP2A6 sequence variants affect smoking behavior (PMID:20418888)
• Concatameric pentamers and pentamers formed from combinations of trimers, dimers, and monomers of alpha6beta2beta3* acetylcholine receptors exhibit similar properties, indicating that the linkers between subunits do not alter their functional properties. (PMID:20923852)
• CHRNB3 and CHRNA6 polymorphisms are associated with smoking behavior and lung cancer susceptibility in Chinese Han population. (PMID:21831805)
• analysis of N-terminal extracellular domain determinants in nicotinic acetylcholine receptor (nAChR) alpha6 subunits that influence effects of wild-type or mutant beta3 subunits on function of alpha6beta2*- or alpha6beta4*-nAChR (PMID:21832048)
• analysis of how nicotinic acetylcholine receptor (nAChR) alpha5 subunits and/or variants modulate function of alpha6*-nAChR (PMID:21873428)
• alpha6beta4* nAChRs are expressed and contribute to exocytosis in human chromaffin cells of the adrenal gland, the main source of adrenaline under stressful situations. (PMID:21917987)
• beta3 subunit coexpression promotes function of alpha6*-nAChR (PMID:22315221)
• Chrna6 has a cellular expression signature for retinal ganglion cells with high correlation to Thy1, a known marker. Immunofluorescence confirms this gene is preferentially expressed by RGCs in the young and adult mouse retina and expression is reduced in glaucoma. (PMID:23002780)
• Cross sectional data of US adults from the NHANES linked with genotype and geocodes were used to identify tobacco use phenotypes, state-level taxation rates, and variation in the nicotinic acetylcholine receptor (CHRNA6) genotype (PMID:23227187)
• Results demonstrate the association between SNPs in CHRNA6 nicotinic acetylcholine receptor genes and the risk of smoking in ADHD (PMID:23899432)
• Elucidation of molecular impediments in the alpha6 subunit for in vitro expression of functional alpha6beta4* nicotinic acetylcholine receptors. (PMID:24085295)
• findings indicate that both CHRNA2 and CHRNA6 play a significant role in the etiology of ND in AA and EA smokers (PMID:24253422)
• The common variant rs13273442 in the CHRNB3-CHNRA6 region is associated significantly with nicotine dependence in European Americans and African Americans. (PMID:24401102)
• the CHRNB3-A6 locus contains multiple variants affecting risk for vulnerability to cocaine and nicotine dependence as well as bipolar disorder, suggesting that they have pleiotropic effects. (PMID:24675634)
• these results demonstrate that the combined effect of rs6474412-C/T polymorphism in smoking-related CHRNB3-CHRNA6 region gene and smoking behavior may not confer risk to psoriasis vulgaris (PV), but may have impact on PV severity in Chinese Han population. (PMID:24792900)
• N-terminal alpha-helix (Asp57); complementary face/inner beta-fold (Arg87 or Asp92) and principal face/outer beta-fold (Ser156 or Asn171) residues in the halpha6 subunit are crucial for functional expression. (PMID:24886653)
• Data show efficient expression of (alpha6beta2)2beta3 nicotinic acetylcholine receptors (AChRs) in Xenopus oocytes using free subunits with only small changes in alpha6 subunits, while not altering AChR pharmacology or channel structure. (PMID:25068303)
• Polymorphism in CHRNA6 gene is associated with esophageal adenocarcinoma. (PMID:25823894)
• More low frequency variants in the CHRNA6/CHRNB3 gene region were observed in cases compared to controls. (PMID:27085880)
• To gain a better understanding of the pathological processes underlying ND and ND-related behaviors and to promote the development of effective smoking cessation therapies, we here present the most recent studies concerning the genetic effects of the CHRNB3-CHRNA6 gene cluster in ND. (PMID:27327258)
• This study is the first showing that CHRNB3/A6 are highly associated with nicotine dependence in a large Chinese Han sample. (PMID:28851948)
• Involvement of CHRNA6 in the Immune Response in Lung Squamous Cell Carcinoma and its Potential as a Drug Target for the Disease. (PMID:37680128)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrna6	ENSDARG00000055559
mus_musculus	Chrna6	ENSMUSG00000031491
rattus_norvegicus	Chrna6	ENSRNOG00000012283

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

Neuronal acetylcholine receptor subunit alpha-6 — Q15825 (reviewed: Q15825)

All UniProt accessions (2): Q15825, E9PP97

UniProt curated annotations — full annotation on UniProt →

Function. Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators. CHRNA6 forms pentameric channels with CHRNB2, CHRNB3 and CHRNA4 that exhibit high sensitivity to ACh and nicotine and are predominantly expressed in only a few brain areas, including dopaminergic neurons, norepirephrine neurons and cells of the visual system. nAChrs containing CHRNA6 subunits mediate endogenous cholinergic modulation of dopamine and gamma-aminobutyric acid (GABA) release in response to nicotine at nerve terminals.

Subunit / interactions. Neuronal AChR is composed of two different types of subunits: alpha and non-alpha (beta). CHRNA6/alpha-6 subunit can be combined to CHRNB2/beta-2, CHRNA4/alpha-4 and CHRNB3/beta-3 to give rise to functional receptors. Heteropentamers containing CHRNB3 have an stoichiometry of (CHRNA6:CHRNB2)2:CHRNB3. Interacts with LYPD6.

Subcellular location. Synaptic cell membrane.

Activity regulation. Activated by a myriad of ligands such as acetylcholine, cytisine and nicotine. CHRNA6 nAChR activity is inhibited by the antagonists alpha-conotoxin MII and PIA, a small disulfide-constrained peptides from cone snails.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-6/CHRNA6 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15825-1	1	yes
Q15825-2	2

RefSeq proteins (2): NP_001186208, NP_004189* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002394	Nicotinic_acetylcholine_rcpt	Family
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR018000	Neurotransmitter_ion_chnl_CS	Conserved_site
IPR036719	Neuro-gated_channel_TM_sf	Homologous_superfamily
IPR036734	Neur_chan_lig-bd_sf	Homologous_superfamily
IPR038050	Neuro_actylchol_rec	Homologous_superfamily

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea), 3 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (15 total): transmembrane region 4, glycosylation site 2, disulfide bond 2, topological domain 2, signal peptide 1, chain 1, splice variant 1, sequence variant 1, modified residue 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8ZRN	ELECTRON MICROSCOPY	3.25
8ZRP	ELECTRON MICROSCOPY	3.32

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15825-F1	80.06	0.56

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): 401

Disulfide bonds (2): 158–172, 222–223

Glycosylation sites (2): 171, 54

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-629594	Highly calcium permeable postsynaptic nicotinic acetylcholine receptors
R-HSA-629597	Highly calcium permeable nicotinic acetylcholine receptors
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-181431	Acetylcholine binding and downstream events
R-HSA-622323	Presynaptic nicotinic acetylcholine receptors
R-HSA-622327	Postsynaptic nicotinic acetylcholine receptors

MSigDB gene sets: 156 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_BEHAVIOR, GOBP_ADULT_BEHAVIOR, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, BLALOCK_ALZHEIMERS_DISEASE_UP, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SECRETION, GOBP_SIGNAL_RELEASE

GO Biological Process (14): signal transduction (GO:0007165), chemical synaptic transmission (GO:0007268), synaptic transmission, cholinergic (GO:0007271), neuromuscular synaptic transmission (GO:0007274), regulation of dopamine secretion (GO:0014059), monoatomic ion transmembrane transport (GO:0034220), response to nicotine (GO:0035094), behavioral response to nicotine (GO:0035095), membrane depolarization (GO:0051899), acetylcholine receptor signaling pathway (GO:0095500), presynaptic modulation of chemical synaptic transmission (GO:0099171), monoatomic ion transport (GO:0006811), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079)

GO Molecular Function (6): acetylcholine receptor activity (GO:0015464), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), protein binding (GO:0005515)

GO Cellular Component (11): plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), cation channel complex (GO:0034703), presynaptic membrane (GO:0042734), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211), dopaminergic synapse (GO:0098691), neurotransmitter receptor complex (GO:0098878), membrane (GO:0016020), synaptic membrane (GO:0097060)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Acetylcholine binding and downstream events	2
Postsynaptic nicotinic acetylcholine receptors	1
Presynaptic nicotinic acetylcholine receptors	1
Transmission across Chemical Synapses	1
Neuronal System	1
Neurotransmitter receptors and postsynaptic signal transmission	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chemical synaptic transmission	2
regulation of membrane potential	2
presynapse	2
postsynaptic neurotransmitter receptor activity	2
monoatomic ion channel complex	2
plasma membrane signaling receptor complex	2
synaptic membrane	2
synapse	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
anterograde trans-synaptic signaling	1
dopamine secretion	1
regulation of catecholamine secretion	1
monoatomic ion transport	1
transmembrane transport	1
response to chemical	1
adult behavior	1
response to nicotine	1
acetylcholine receptor activity	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
modulation of chemical synaptic transmission	1
transport	1
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
transmembrane signaling receptor activity	1
synaptic transmission, cholinergic	1
acetylcholine binding	1
excitatory extracellular ligand-gated monoatomic ion channel activity	1
ligand-gated monoatomic cation channel activity	1
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	1
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1
binding	1
membrane	1

Protein interactions and networks

STRING

884 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNA6	CYP2A6	P00190	734
CHRNA6	IGBP1	P78318	654
CHRNA6	CYP2B6	P20813	627
CHRNA6	CHRNB3	Q05901	567
CHRNA6	EGLN2	Q96KS0	537
CHRNA6	SLC17A6	Q9P2U8	516
CHRNA6	GABBR2	O75899	468
CHRNA6	CHRM5	P08912	463
CHRNA6	CHAT	P28329	445
CHRNA6	CD7	P09564	426
CHRNA6	CHRM2	P08172	424
CHRNA6	CHRNE	Q04844	415
CHRNA6	DRD1	P21728	413
CHRNA6	CHRNA4	P43681	412
CHRNA6	DDC	P20711	402

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PPP3R1	CHRNA6	psi-mi:“MI:0915”(physical association)	0.490
LYPD6	CHRNB2	psi-mi:“MI:0914”(association)	0.350
LYNX1	CHRNB2	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): CHRNA6 (Two-hybrid)

ESM2 similar proteins: A8WQK3, O16926, P02708, P02709, P02710, P02711, P02712, P02718, P04755, P04756, P04757, P05377, P09478, P09479, P09481, P09484, P09628, P12389, P12392, P17644, P18845, P19370, P20420, P22456, P23414, P25108, P25162, P26152, P26153, P30926, P32297, P43143, P48180, P48181, P49579, P49581, P91766, Q07263, Q15825, Q23022

Diamond homologs: A5X5Y0, O70212, O95264, P04757, P05376, P18845, P19370, P22770, P23979, P26153, P32297, P35563, P36544, P43143, P43679, P46098, P48182, P49581, P49582, P54131, Q05941, Q07263, Q15825, Q494W8, Q5IS76, Q68RJ7, Q70Z44, Q866A2, Q8R4G9, Q8WXA8, Q9I8C7, Q9JHJ5, Q9JJ16, A8WQK3, O16926, O70174, P02708, P02709, P02710, P02711

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CHRNA6	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta4”	binding
CHRNA6	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta2-beta3”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	48
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1807741	GRCh37/hg19 8p11.21(chr8:42303398-43002481)x1	Pathogenic
563508	GRCh37/hg19 8p11.21(chr8:42303397-43002481)x1	Pathogenic
153159	GRCh38/hg38 8p11.21(chr8:42236286-42758909)x1	Likely pathogenic
236030	Single allele	Likely pathogenic

SpliceAI

1041 predictions. Top by Δscore:

Variant	Effect	Δscore
8:42756825:C:CC	acceptor_gain	1.0000
8:42756926:A:AC	donor_gain	1.0000
8:42756927:C:CC	donor_gain	1.0000
8:42756953:T:TA	donor_gain	1.0000
8:42756964:T:C	donor_gain	1.0000
8:42765201:CAGC:C	acceptor_gain	1.0000
8:42755847:T:TA	donor_gain	0.9900
8:42765059:ACTCA:A	donor_loss	0.9900
8:42765061:T:TA	donor_loss	0.9900
8:42765063:A:T	donor_loss	0.9900
8:42765063:AC:A	donor_gain	0.9900
8:42765064:CC:C	donor_gain	0.9900
8:42765064:CCA:C	donor_gain	0.9900
8:42765064:CCACG:C	donor_gain	0.9900
8:42765202:AGCCT:A	acceptor_loss	0.9900
8:42765203:GC:G	acceptor_gain	0.9900
8:42765203:GCCTG:G	acceptor_loss	0.9900
8:42765204:CC:C	acceptor_gain	0.9900
8:42765204:CCTGT:C	acceptor_loss	0.9900
8:42765205:C:CC	acceptor_gain	0.9900
8:42765205:CTGT:C	acceptor_loss	0.9900
8:42765206:T:A	acceptor_loss	0.9900
8:42756820:CAGCA:C	acceptor_gain	0.9800
8:42765063:A:AC	donor_gain	0.9800
8:42765064:C:CC	donor_gain	0.9800
8:42767900:A:AC	donor_gain	0.9800
8:42767901:C:CC	donor_gain	0.9800
8:42758983:A:AC	donor_gain	0.9700
8:42765061:TCAC:T	donor_gain	0.9700
8:42765062:CACC:C	donor_gain	0.9700

AlphaMissense

3284 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:42756581:C:A	W206C	0.998
8:42756581:C:G	W206C	0.998
8:42756954:C:A	W116C	0.998
8:42756954:C:G	W116C	0.998
8:42756956:A:G	W116R	0.998
8:42756956:A:T	W116R	0.998
8:42757011:C:A	W97C	0.997
8:42757011:C:G	W97C	0.997
8:42757013:A:G	W97R	0.997
8:42757013:A:T	W97R	0.997
8:42757034:A:G	W90R	0.997
8:42757034:A:T	W90R	0.997
8:42756486:C:G	R238T	0.996
8:42756583:A:G	W206R	0.996
8:42756583:A:T	W206R	0.996
8:42756731:A:C	S156R	0.996
8:42756731:A:T	S156R	0.996
8:42756733:T:G	S156R	0.996
8:42756413:A:C	F262L	0.995
8:42756413:A:T	F262L	0.995
8:42756415:A:G	F262L	0.995
8:42756485:T:A	R238S	0.995
8:42756485:T:G	R238S	0.995
8:42756683:A:C	C172W	0.995
8:42756684:C:G	C172S	0.995
8:42756685:A:T	C172S	0.995
8:42756705:A:C	F165C	0.995
8:42757032:C:A	W90C	0.995
8:42757032:C:G	W90C	0.995
8:42756210:C:G	R330P	0.994

dbSNP variants (sampled 300 via entrez): RS1000107126 (8:42760088 A>T), RS1000174694 (8:42761075 C>G,T), RS1000460628 (8:42766065 G>A), RS1000541384 (8:42760239 GCACACTCATGCACACT>G), RS1000773572 (8:42767762 A>G), RS1000877795 (8:42761804 C>T), RS1001192076 (8:42754376 C>G), RS1001485856 (8:42755029 C>A,G), RS1001623462 (8:42754144 C>T), RS1002180317 (8:42753338 G>A), RS1002268969 (8:42767247 A>C,G), RS1002368260 (8:42761056 C>T), RS1002422089 (8:42761531 G>C), RS1002568530 (8:42758199 A>C,G), RS1002758541 (8:42770539 G>A)

Disease associations

OMIM: gene MIM:606888 | disease phenotypes: MIM:213600, MIM:606656

GenCC curated gene-disease

Mondo (1): basal ganglia calcification, idiopathic, 1 (MONDO:0024538)

Orphanet (1): Bilateral striopallidodentate calcinosis (Orphanet:1980)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000667_4	Smoking behavior	1.000000e-08
GCST003185_3	Nicotine dependence	1.000000e-06
GCST003225_24	Pelvic organ prolapse (moderate/severe)	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537657	Basal ganglia calcification, idiopathic 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2109233 (PROTEIN COMPLEX), CHEMBL2109237 (PROTEIN COMPLEX), CHEMBL3137285 (PROTEIN COMPLEX), CHEMBL4524133 (PROTEIN COMPLEX GROUP), CHEMBL4804182 (PROTEIN COMPLEX GROUP), CHEMBL4888445 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 184,969 (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
CHEMBL3	NICOTINE	4	184,969

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2217732	CHRNA6		0.00	0
rs1072003	CHRNA6		0.00	0
rs2304297	CHRNA6		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Nicotinic acetylcholine receptors (nACh)

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
[3H]epibatidine	Full agonist	10.46	pKd
mecamylamine	Channel blocker	4.96	pIC50
hexamethonium	Channel blocker	4.04	pIC50

Binding affinities (BindingDB)

3 measured of 3 human assays (3 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3329540	EC50	53 nM
CHEMBL3329544	KI	310 nM
CHEMBL3329545	EC50	540 nM

ChEMBL bioactivities

126 potent at pChembl≥5 of 130 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.22	Ki	0.06	nM	CHEMBL5412811
10.11	Ki	0.077	nM	CHEMBL5404069
9.80	IC50	0.16	nM	CHEMBL594330
9.70	IC50	0.2	nM	CHEMBL4869892
9.62	IC50	0.24	nM	CHEMBL4860756
9.59	IC50	0.26	nM	CHEMBL595286
9.55	IC50	0.28	nM	CHEMBL4876825
9.44	Ki	0.36	nM	CHEMBL5404578
9.41	IC50	0.39	nM	CHEMBL595311
9.39	IC50	0.41	nM	CHEMBL4878931
9.30	Ki	0.5	nM	CHEMBL5438932
9.17	Ki	0.67	nM	CHEMBL5430462
9.02	Ki	0.95	nM	CHEMBL2177538
9.02	IC50	0.95	nM	CHEMBL3104238
9.02	Ki	0.95	nM	CHEMBL5423438
9.02	IC50	0.95	nM	CHEMBL595047
9.00	Ki	1	nM	CHEMBL2177537
9.00	IC50	1	nM	CHEMBL406906
8.84	IC50	1.46	nM	CHEMBL4872474
8.83	IC50	1.49	nM	CHEMBL4468892
8.82	IC50	1.5	nM	CHEMBL5087554
8.70	IC50	2	nM	CHEMBL4462168
8.66	IC50	2.2	nM	CHEMBL4439678
8.65	IC50	2.24	nM	CHEMBL4878856
8.59	Ki	2.6	nM	CHEMBL2177543
8.55	IC50	2.84	nM	CHEMBL4461998
8.54	IC50	2.9	nM	CHEMBL4454928
8.52	IC50	3	nM	CHEMBL609593
8.45	IC50	3.52	nM	CHEMBL4865365
8.32	Ki	4.8	nM	CHEMBL2177545
8.26	IC50	5.55	nM	CHEMBL4872191
8.24	IC50	5.7	nM	CHEMBL4474223
8.17	IC50	6.75	nM	CHEMBL3104239
8.13	EC50	7.4	nM	CHEMBL2024094
8.08	IC50	8.3	nM	CHEMBL2409631
8.05	EC50	9	nM	CHEMBL2409627
8.03	IC50	9.24	nM	CHEMBL4461702
8.02	IC50	9.64	nM	CHEMBL4459917
8.01	IC50	9.7	nM	CHEMBL2024094
7.97	IC50	10.7	nM	CHEMBL4867074
7.92	IC50	12	nM	CHEMBL5086388
7.90	IC50	12.6	nM	CHEMBL4538537
7.89	IC50	12.8	nM	CHEMBL4458975
7.87	IC50	13.4	nM	CHEMBL4583045
7.85	Ki	14	nM	CHEMBL3329543
7.79	IC50	16.2	nM	CHEMBL4847671
7.74	IC50	18.2	nM	CHEMBL4516107
7.72	IC50	18.9	nM	CHEMBL4476528
7.68	Ki	21	nM	CHEMBL3329528
7.68	IC50	21	nM	CHEMBL4470868

PubChem BioAssay actives

126 with measured affinity, of 263 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
2-chloro-5-[(3S)-3-methyl(511C)pentyl]-3-[(E)-2-pyridin-4-ylethenyl]pyridine	1988843: Binding affinity to nACh alpha6beta2 receptor (unknown origin) assessed as inhibition constant	ki	0.0001	uM
6-[5-(2-(18F)fluoro-3-pyridinyl)-3-pyridinyl]-8-methyl-8-azabicyclo[3.2.1]octane	1988843: Binding affinity to nACh alpha6beta2 receptor (unknown origin) assessed as inhibition constant	ki	0.0001	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(3-carbamimidamidopropyl)-6-carbamoyl-48-(hydroxymethyl)-21,30,45-tris(1H-imidazol-5-ylmethyl)-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27,36-di(propan-2-yl)-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0002	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24,30-bis(2-amino-2-oxoethyl)-9-[(2S)-butan-2-yl]-6-carbamoyl-48-(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27,36-di(propan-2-yl)-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0002	uM
(2R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-sulfanylpropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoic acid	450500: Inhibition of alpha6beta2 nAChR	ic50	0.0002	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-30-(2-amino-2-oxoethyl)-24-(3-carbamimidamidopropyl)-6-carbamoyl-48-(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27,36-di(propan-2-yl)-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0003	uM
(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-3-sulfanylpropanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-sulfanylpropanoic acid	450500: Inhibition of alpha6beta2 nAChR	ic50	0.0003	uM
3-[[(2S)-2,5-dihydro-1H-pyrrol-2-yl]methoxy]-5-(3-(18F)fluoropropyl)pyridine	1988843: Binding affinity to nACh alpha6beta2 receptor (unknown origin) assessed as inhibition constant	ki	0.0004	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-9-[(2S)-butan-2-yl]-24-(3-carbamimidamidopropyl)-6-carbamoyl-48-(hydroxymethyl)-21,30,45-tris(1H-imidazol-5-ylmethyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27,36-di(propan-2-yl)-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0004	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-sulfanylpropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(1R)-1-carboxy-2-sulfanylethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	450500: Inhibition of alpha6beta2 nAChR	ic50	0.0004	uM
2-(18F)fluoro-3-[[(2S)-1-methyl-2,5-dihydropyrrol-2-yl]methoxy]pyridine	1988843: Binding affinity to nACh alpha6beta2 receptor (unknown origin) assessed as inhibition constant	ki	0.0005	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-(3-(18F)fluoropropyl)pyridine	1988843: Binding affinity to nACh alpha6beta2 receptor (unknown origin) assessed as inhibition constant	ki	0.0007	uM
(3S)-4-[(2S)-2-[[(2R)-1-[[(2R)-1-[[(2S)-1-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-1-[[(2R)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-5-amino-1-[[(2S,3S)-1-[[(1R)-1-carboxy-2-sulfanylethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-4-oxobutanoic acid	450500: Inhibition of alpha6beta2 nAChR	ic50	0.0009	uM
6-[5-(6-(18F)fluoro-2-pyridinyl)-3-pyridinyl]-8-methyl-8-azabicyclo[3.2.1]octane	1988843: Binding affinity to nACh alpha6beta2 receptor (unknown origin) assessed as inhibition constant	ki	0.0009	uM
(1S,5R)-7-pyridin-3-yl-3-azabicyclo[3.3.1]non-6-ene	705800: Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	ki	0.0009	uM
(3S)-3-[[(2S)-2-amino-5-carbamimidamidopentanoyl]amino]-4-[(2S)-2-[[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-21,45-bis(2-amino-2-oxoethyl)-12-(3-amino-3-oxopropyl)-9-[(2S)-butan-2-yl]-6-carbamoyl-30-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-24-(1H-imidazol-5-ylmethyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27,36-di(propan-2-yl)-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-53-yl]carbamoyl]pyrrolidin-1-yl]-4-oxobutanoic acid	1062465: Antagonist activity at human alpha6/alpha3beta2beta3 nAChR expressed in Xenopus oocytes assessed as inhibition of ACh-induced current by voltage clamp electrophysiology method	ic50	0.0009	uM
(3S)-3-amino-4-[(2S)-2-[[(2R)-1-[[(2R)-1-[[(2S)-1-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-1-[[(2R)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[(2S)-2-[[(2S)-5-amino-1-[[(2S,3S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,4-dioxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-4-oxobutanoic acid	242400: Inhibitory concentration against Nicotinic acetylcholine receptor alpha-6-alpha-3-beta-2-beta-3; Range is 0.7-1 nM	ic50	0.0010	uM
(1R,5S)-7-pyridin-3-yl-3-azabicyclo[3.3.1]non-6-ene	705800: Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	ki	0.0010	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(4-aminobutyl)-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0015	uM
2-[[(1R,4S,10S,16S,19S,22R,27S,30S,33S,36S,39S,46R)-46-[(2-aminoacetyl)amino]-16-[(1R)-1-hydroxyethyl]-19-(hydroxymethyl)-30-[(4-hydroxyphenyl)methyl]-39-methyl-33-(2-methylpropyl)-3,9,15,18,21,29,32,35,38,41,47-undecaoxo-36-propan-2-yl-24,25,43,44-tetrathia-2,8,14,17,20,28,31,34,37,40,48-undecazatetracyclo[20.19.7.04,8.010,14]octatetracontane-27-carbonyl]amino]acetic acid	1831938: Antagonist activity at rat alpha6/alpha3beta4 nAChR expressed in xenopus oocytes assessed as inhibition of Ach- induced response at -70 mV holding potential preincubated for 5 mins followed by Ach stimulation by voltage-clamp based electrophysiological method	ic50	0.0015	uM
3-[(1R,6R,9S,12S,15S,18S,21S,24S,27S,30R,33S,36S,42S,45S,50R)-50-[(2-aminoacetyl)amino]-12,42-bis(2-amino-2-oxoethyl)-6-carbamoyl-15,45-bis(hydroxymethyl)-18,27-bis(1H-imidazol-5-ylmethyl)-9,24-bis(2-methylpropyl)-8,11,14,17,20,23,26,29,32,35,41,44,47,49-tetradecaoxo-33-propan-2-yl-3,4,52,53-tetrathia-7,10,13,16,19,22,25,28,31,34,40,43,46,48-tetradecazatricyclo[28.17.7.036,40]tetrapentacontan-21-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0015	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-6-carbamoyl-30-[(1R)-1-hydroxyethyl]-48-(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0020	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24,30-bis(2-amino-2-oxoethyl)-6-carbamoyl-48-(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0022	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-6-carbamoyl-24-[3-(diaminomethylideneamino)propyl]-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0022	uM
7-(5-propan-2-yloxy-3-pyridinyl)-3-azabicyclo[3.3.1]non-6-ene	705800: Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	ki	0.0026	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-9-[(2S)-butan-2-yl]-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0028	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-6-carbamoyl-48-(hydroxymethyl)-21,30,45-tris(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0029	uM
(2R)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S)-4-amino-2-[[2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-sulfanylpropanoyl]amino]propanoyl]amino]acetyl]amino]-4-oxobutanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-methylpentanoyl]amino]-3-sulfanylpropanoic acid	450500: Inhibition of alpha6beta2 nAChR	ic50	0.0030	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27,36-di(propan-2-yl)-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0035	uM
7-(5-phenoxy-3-pyridinyl)-3-azabicyclo[3.3.1]non-6-ene	705800: Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	ki	0.0048	uM
(1R,6R,9S,12S,15S,18S,21S,24S,27S,30R,33S,36S,42S,45S,50R)-50-[(2-aminoacetyl)amino]-15,21,27-tris(3-carbamimidamidopropyl)-45-(hydroxymethyl)-18,42-bis(1H-imidazol-5-ylmethyl)-12,24-dimethyl-9-(2-methylpropyl)-8,11,14,17,20,23,26,29,32,35,41,44,47,49-tetradecaoxo-33-propan-2-yl-3,4,52,53-tetrathia-7,10,13,16,19,22,25,28,31,34,40,43,46,48-tetradecazatricyclo[28.17.7.036,40]tetrapentacontane-6-carboxamide	1753076: Inhibition of human alpha6/alpha3beta2beta3 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response by two-electrode voltage-clamp method	ic50	0.0056	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-9,27-di(propan-2-yl)-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0057	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0067	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-[(1S,2R)-2-(2-methoxyethyl)cyclopropyl]pyridine	761160: Agonist activity at human alpha6/alpha3beta2beta3 nAChR expressed in human SHEP1 cells assessed as stimulation of 86Rb+ ion efflux after 5 mins by liquid scintillation counting analysis	ec50	0.0074	uM
3-[(1S,2R)-2-(2-methoxyethyl)cyclopropyl]-5-[[(3R)-pyrrolidin-3-yl]methoxy]pyridine;2,2,2-trifluoroacetic acid	761152: Antagonist activity at human alpha6/alpha3beta2beta3 nAChR expressed in human SHEP1 cells assessed as inhibition of carbamylcholine-induced 86Rb+ ion efflux preincubated for 10 mins by liquid scintillation counting analysis	ic50	0.0083	uM
3-[(1S,2R)-2-(2-methoxyethyl)cyclopropyl]-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine;2,2,2-trifluoroacetic acid	761160: Agonist activity at human alpha6/alpha3beta2beta3 nAChR expressed in human SHEP1 cells assessed as stimulation of 86Rb+ ion efflux after 5 mins by liquid scintillation counting analysis	ec50	0.0090	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-27-[(2S)-butan-2-yl]-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0092	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9,27-bis(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0096	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-24,36-dimethyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0107	uM
2-[[(1R,4S,10S,16S,19S,22R,27S,30S,33S,36S,39S,46R)-46-[(2-aminoacetyl)amino]-12-hydroxy-16-[(1R)-1-hydroxyethyl]-19-(hydroxymethyl)-30-[(4-hydroxyphenyl)methyl]-39-methyl-33-(2-methylpropyl)-3,9,15,18,21,29,32,35,38,41,47-undecaoxo-36-propan-2-yl-24,25,43,44-tetrathia-2,8,14,17,20,28,31,34,37,40,48-undecazatetracyclo[20.19.7.04,8.010,14]octatetracontane-27-carbonyl]amino]acetic acid	1831996: Antagonist activity at rat alpha6/alpha3beta4 nAChR	ic50	0.0120	uM
(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-12-(3-amino-3-oxopropyl)-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontane-6-carboxamide	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0126	uM
2-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]acetic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0128	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-27-butyl-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0134	uM
3,6-diazabicyclo[3.1.1]heptan-3-yl-[(1R,2R)-2-methylcyclopropyl]methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.0140	uM
(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-12,24-bis(2-amino-2-oxoethyl)-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontane-6-carboxamide	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0162	uM
2-[[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]methyl]propanedioic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0182	uM
5-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-6-carbamoyl-12-(2-carboxyethyl)-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-24-yl]pentanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0189	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-9-butyl-6-carbamoyl-30,48-bis(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36-methyl-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0210	uM
cyclopropyl(3,6-diazabicyclo[3.1.1]heptan-3-yl)methanone	1188741: Displacement of [3H]epibatidine from human alpha6/alpha3beta2beta3 nAChR transfected in CHO cells by liquid scintillation counting	ki	0.0210	uM
3-[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-53-[(2-aminoacetyl)amino]-24-(2-amino-2-oxoethyl)-6-carbamoyl-30-(hydroxymethyl)-21,45-bis(1H-imidazol-5-ylmethyl)-36,48-dimethyl-9-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-27-propan-2-yl-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-12-yl]propanoic acid	1753051: Inhibition of human alpha6/alpha3beta4 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response measured after 5 min by two-electrode voltage-clamp method	ic50	0.0220	uM

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation	2
Nicotine	decreases expression, increases expression	2
abrine	increases expression	1
Acetaminophen	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Tobacco Smoke Pollution	affects response to substance	1
Valproic Acid	decreases methylation	1
Cadmium Chloride	increases expression	1

ChEMBL screening assays

34 unique, capped per target: 33 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2187460	Binding	Displacement of [125I]epibatidine from human alpha6/alpha3beta2beta3 nAChR expressed in HEK293T cells	Structure-activity studies of 7-heteroaryl-3-azabicyclo[3.3.1]non-6-enes: a novel class of highly potent nicotinic receptor ligands. — J Med Chem
CHEMBL4810209	ADMET	Inhibition of neuronal nicotinic receptor (unknown origin) at 0.1 to 1 uM	Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1KG	PrecisION hnAChR alpha4/alpha6/beta2-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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