CHRNA3

Summary

CHRNA3 (cholinergic receptor nicotinic alpha 3 subunit, HGNC:1957) is a protein-coding gene on chromosome 15q25.1, encoding Neuronal acetylcholine receptor subunit alpha-3 (P32297). 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 locus encodes a member of the nicotinic acetylcholine receptor family of proteins. Members of this family of proteins form pentameric complexes comprised of both alpha and beta subunits. This locus encodes an alpha-type subunit, as it contains characteristic adjacent cysteine residues. The encoded protein is a ligand-gated ion channel that likely plays a role in neurotransmission. Polymorphisms in this gene have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 1136 — RefSeq curated summary.

At a glance

• Gene–disease (curated): urinary bladder, atony of (Strong, GenCC)
• GWAS associations: 161
• Clinical variants (ClinVar): 209 total — 5 pathogenic, 11 likely-pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes — 21 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000743

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1957
Approved symbol	CHRNA3
Name	cholinergic receptor nicotinic alpha 3 subunit
Location	15q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000080644
Ensembl biotype	protein_coding
OMIM	118503
Entrez	1136

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000326828, ENST00000348639, ENST00000558903, ENST00000559002, ENST00000559080, ENST00000559658, ENST00000559941, ENST00000561128, ENST00000893003

RefSeq mRNA: 2 — MANE Select: NM_000743 NM_000743, NM_001166694

CCDS: CCDS10305, CCDS53964

Canonical transcript exons

ENST00000326828 — 6 exons

Exon	Start	End
ENSE00000794038	78617024	78617133
ENSE00000794039	78618617	78618661
ENSE00001160226	78601253	78602264
ENSE00001371145	78595309	78596732
ENSE00001423049	78620713	78620996
ENSE00003609585	78618776	78618915

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 99.14.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1934 / max 347.3583, expressed in 301 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151115	1.2422	193
151116	0.3093	109
151114	0.2418	45
151117	0.2021	33
151118	0.1337	36
151119	0.0583	16
151120	0.0060	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	99.14	gold quality
thymus	UBERON:0002370	93.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.80	gold quality
buccal mucosa cell	CL:0002336	84.86	gold quality
secondary oocyte	CL:0000655	84.02	gold quality
oocyte	CL:0000023	83.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.24	gold quality
muscle layer of sigmoid colon	UBERON:0035805	80.08	gold quality
sigmoid colon	UBERON:0001159	76.69	gold quality
lateral nuclear group of thalamus	UBERON:0002736	76.09	gold quality
type B pancreatic cell	CL:0000169	75.63	gold quality
vermiform appendix	UBERON:0001154	75.42	gold quality
rectum	UBERON:0001052	74.72	gold quality
olfactory bulb	UBERON:0002264	74.35	gold quality
caecum	UBERON:0001153	73.95	gold quality
colon	UBERON:0001155	73.49	gold quality
large intestine	UBERON:0000059	73.34	gold quality
tongue squamous epithelium	UBERON:0006919	72.82	gold quality
transverse colon	UBERON:0001157	72.03	gold quality
intestine	UBERON:0000160	71.73	gold quality
ganglionic eminence	UBERON:0004023	71.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	71.45	gold quality
CA1 field of hippocampus	UBERON:0003881	70.50	gold quality
diaphragm	UBERON:0001103	69.67	gold quality
cerebellum	UBERON:0002037	69.57	gold quality
cerebellar cortex	UBERON:0002129	69.49	gold quality
cerebellar hemisphere	UBERON:0002245	69.21	gold quality
epithelial cell of pancreas	CL:0000083	68.62	gold quality
apex of heart	UBERON:0002098	68.30	gold quality
embryo	UBERON:0000922	67.95	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	339.88
E-MTAB-7316	yes	23.52
E-GEOD-135922	yes	13.77
E-HCAD-10	yes	3.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, ETS1, HIF1A, MYC, PHOX2A, POU3F1, RORA, SOX10, SP1, THRA

miRNA regulators (miRDB)

57 targeting CHRNA3, 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-3185	99.99	68.12	1959
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-129-1-3P	98.86	68.41	779

Literature-anchored findings (GeneRIF, showing 40)

• Changes in nicotinic acetylcholine receptor subunits expression in brain of patients with Down syndrome and Alzheimer’s disease. (PMID:11771745)
• CHRNA3 and CHRNA4 genes and AD. Two novel missense point mutations, Ser413Leu in the CHRNA4 gene and Gln397Pro in the CHRNB2 gene, were identified in two different AD cases but were not found in other AD cases and controls. (PMID:12214130)
• CHRNA3 subunit is expressed in the soma of the majority of pyramidal cells, with the most alpha 3 immunoreactivity observed in CA2-4 and entorhinal cortex and relatively less in CA1 and subicular pyramidal cell soma. (PMID:12663058)
• absence of differences in the pharmacological profile of nicotinic receptor alpha3beta4 argues against role for incorporated beta3 subunit in formation of agonist binding sites while changes in channel kinetics suggest important effect on receptor gating (PMID:12912995)
• alpha3 and alpha7 nicotinic acetylcholine receptors regulate keratinocyte chemokinesis and chemotaxis (PMID:15494367)
• alpha3beta2 nicotinic receptor has a role in regulating gene expression after tobacco exposure in oral epithelial cells (PMID:15681842)
• the alpha3 subunit is expressed in every terminally differentiated ganglionic cell, this is the first example of a “pan-autonomic” gene whose expression is regulated by PHOX2 proteins. (PMID:17344216)
• Reporter gene analysis demonstrated that this sequence, termed “alpha3 intron 5,” inhibits the transcriptional activities of the alpha3 and beta4 subunit gene promoters (PMID:17504758)
• A common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to nicotine dependence. (PMID:18227835)
• CHRNA5 and CHRNA3 are promising candidate genes in the region of 15q25.1 for lung cancer. (PMID:18385676)
• In the 2,827 long-term smokers examined, common susceptibility and protective haplotypes at the CHRNA5-A3-B4 locus were associated with nicotine dependence severity. (PMID:18618000)
• alpha3 nAChR may improve cleavage of APP by alpha-secretase, enhance antioxidation and inhibit the toxicity of Abeta, suggesting that the receptor might play an important role in AD. (PMID:18647633)
• Correlated SNPs in the cholinergic nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4, in a case-control study of cocaine dependence composed of 504 European-American and 583 African-Americans. (PMID:18759969)
• CHRNA3 seem to exert no relevant influence on smoking cessation probability in heavy smokers in the general population. (PMID:18996504)
• smokers who carry the CHRNA3 and CHRNA5 variants are expected to be at increased risk for lung cancer compared with smokers who do not carry these alleles. (PMID:19010884)
• Two distinct variant groups in the CHRNA5-CHRNA3-CHRNB4 gene cluster are strongly associated with heavy smoking. The snp rs16969968 alters the coding sequence of these genes. (PMID:19029397)
• The alpha5 and alpha3 subunits play a significant role in both nicotine dependence and alcohol abuse/dependence. (PMID:19132693)
• The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD. (PMID:19300482)
• Genetic variant in the CHRNA5-CHRNA3-CHRNB4 gene cluster is associated with smoking cessation during pregnancy. (PMID:19429911)
• The detection of alpha3-AChR autoantibody aids the diagnosis of neurological autoimmunity and cancer. (PMID:19506133)
• Missense mutation of CHRNB4, CHRNB3 and CHRNA4 are associated with sporadic amyotrophic lateral sclerosis. (PMID:19628475)
• Genetic variation at CHRNA5/CHRNA3/CHRNB4 cluster influences blood nicotine level. (PMID:19628476)
• Single Nucleotide Polymorphism in CHRNA3 is associated with non-small cell lung cancer. (PMID:19641473)
• The CHRNA3 SNP rs578776 is associated with nicotine dependence in European-Americans but not in African-Americans (PMID:19706762)
• single nucleotide polymorphisms influence treatment outcome in advanced non-small-cell lung cancer patients (PMID:19733931)
• These results indicate that variants within CHRNA3 and among CHRNA5, CHRNA3, and CHRNB4 contribute significantly to the etiology of ND through gene-gene interactions. (PMID:19859904)
• Loop 9 has a different role in the function of homomeric and heteromeric receptors. (PMID:20043866)
• Single nucleotide polymorphisms in the CHRNA3 gene is associated with lung cancer. (PMID:20234319)
• These results suggest that sensorimotor gating is influenced by variations of the CHRNA3 gene, which might also have an impact on the course and severity of schizophrenia. (PMID:20393456)
• Data suggest that interactions between alpha3beta4 nAChRs and P2X2 receptors may modulate transmission at enteric synapses that use ATP and acetylcholine as co-transmitters. (PMID:20426799)
• The data of this study supported the importance of variants in the CHRNA5/A3/B4 gene cluster as mediators of the genetic risk for substance dependence. (PMID:20485328)
• Variation in the nicotinic acetylcholine receptor gene cluster CHRNA5-CHRNA3-CHRNB4 influences cognitive flexibility differently in African Americans compared to European Americans. (PMID:20631687)
• findings suggest that both CHNA5 Asp398Asn and CHRNA3 rs578776 are associated with smoking. (PMID:20643934)
• The CHRNA3/5 locus was associated with increased smoking intensity and emphysema in individuals with COPD (PMID:20656943)
• This review focuses on the clustered nicotinic acetylcholine receptor genes CHRNalpha5/alpha3/beta4 and evaluates their role in nicotine addiction and lung cancer. (PMID:20685379)
• associations of variants in the CHRNA5/A3/B4 cluster with smoking initiation, smoking quantity and smoking cessation (PMID:20808433)
• evidence that CHRNA5-CHRNA3-CHRNB4 gene cluster variants,particularly CHRNA5 variant rs16969968, could be associated with cognitive performance possibly mediating in part risk for developing nicotine dependence (PMID:20886544)
• CHRNA5-CHRNA3-CHRNB4 is involved in the transition toward heavy smoking in mid-adulthood and in smoking persistence. (PMID:21168125)
• Single nucleotide polymorphism (SNP) CHRNA3 on chromosome 15 is not associated with Parkinson’s disease risk in the overall anaylsis or after stratifying on smoking status. (PMID:21228559)
• Variant A of the rs1051730 SNP of CHRNA5-A3-B4 gene cluster was significantly associated with smoking quantity in 2 Italian populations, Val Borbera and Cilento, no association was found in Carlantino population. (PMID:21248747)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrna3	ENSDARG00000100991
mus_musculus	Chrna3	ENSMUSG00000032303
rattus_norvegicus	Chrna3	ENSRNOG00000013829

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), 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), CHRNA6 (ENSG00000147434), 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-3 — P32297 (reviewed: P32297)

All UniProt accessions (2): P32297, H0YNF9

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. CHRNA3 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4, with CHRNA5, and CHRNB3 as accesory subunits. CHRNA3:CHRNB4 being predominant in neurons of the autonomic ganglia, it is known as ganglionic nicotinic receptor. CHRNA3:CHRNB4 or CHRNA3:CHRNA5:CHRNB4 play also an important role in the habenulo-interpeduncular tract, modulating the mesolimbic dopamine system and affecting reward circuits and addiction. Hypothalamic CHRNA3:CHRNB4 nAChR activation by nicotine leads to activation of POMC neurons and a decrease in food intake. Also expressed in the urothelium where it modulates reflex bladder activity by increasing intracellular calcium through extracellular influx and basal ATP release.

Subunit / interactions. Neuronal AChR is composed of two different types of subunits: alpha and beta. CHRNA3/Alpha-3 subunit can be combined to CHRNA5/alpha-5, CHRNB2/beta-2 CHRNB3/beta-3 or CHRNB4/beta-4 to give rise to functional receptors. Forms stoichiometries such as (CHRNA3)2:(CHRNB4)3 or (CHRNA3:CHRNB4)2:CHRNB3. Part of a complex composed of STUB1/CHIP, VCP/p97, CHRNA3, and UBXN2A that modulates the ubiquitination and endoplasmic reticulum-associated degradation (ERAD) of CHRNA3. Within the complex UBXN2A acts as a scaffold protein required for the interaction of CHRNA3 with VCP/p97, this interaction also inhibits CHRNA3 ubiquitination by STUB1/CHIP and subsequently ERAD. Interacts with UBXN2A (via SEP domain), the interaction is required for the interaction of CHRNA3 in the STUB1:VCP:UBXN2A complex. Interacts with RIC3; which is required for proper folding and assembly. Interacts with LYPD6.

Subcellular location. Synaptic cell membrane. Cell membrane. Endoplasmic reticulum. Golgi apparatus.

Post-translational modifications. Ubiquitinated; by STUB1/CHIP and thereafter degraded by the 26S proteosome complex.

Disease relevance. Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT (BAIPRCK) [MIM:191800] An autosomal recessive disease characterized by impaired innervation and autonomic dysfunction of the urinary bladder, hydronephrosis, vesicoureteral reflux, small kidneys, recurrent urinary tract infections, and progressive renal insufficiency. Additional autonomic features are impaired pupillary reflex and orthostatic hypotension. The disease manifests in utero or early childhood. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine. The heteropentamer CHRNA3:CHRNB2 activity is blocked by alpha-conotoxins ImI, ImII, PnIA, GID and MII. The heteropentamer CHRNA3:CHRNB4 activity is blocked by the alpha-conotoxin ImI and AuIB.

Polymorphism. Genetic variations in CHRNA3 have been associated with susceptibility to smoking-related behavioral traits and lung cancer, contributing to the smoking quantitative trait locus 3 (SQTL3) [MIM:612052].

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-3/CHRNA3 sub-subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P32297-2	2	yes
P32297-1	1
P32297-3	3

RefSeq proteins (2): NP_000734, NP_001160166 (=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 (60 total): strand 15, helix 10, sequence conflict 6, turn 6, topological domain 5, transmembrane region 4, sequence variant 3, modified residue 2, glycosylation site 2, disulfide bond 2, splice variant 2, signal peptide 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4ZK4	X-RAY DIFFRACTION	1.9
5TVC	X-RAY DIFFRACTION	1.93
5SYO	X-RAY DIFFRACTION	2
6PV7	ELECTRON MICROSCOPY	3.34
6PV8	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32297-F1	81.97	0.62

Antibody-complex structures (SAbDab): 2 — 6PV7, 6PV8

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 (2): 413, 416

Disulfide bonds (2): 159–173, 223–224

Glycosylation sites (2): 55, 172

Mutagenesis-validated functional residues (1):

Position	Phenotype
279	increases potency of agonists.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-629587	Highly sodium permeable postsynaptic acetylcholine nicotinic receptors
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: 255 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_DENDRITE_DEVELOPMENT, GOBP_EXCRETION, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_328, GOBP_BEHAVIOR, GOBP_ADULT_BEHAVIOR, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_NEUROGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING

GO Biological Process (19): monoatomic ion transport (GO:0006811), regulation of smooth muscle contraction (GO:0006940), signal transduction (GO:0007165), synaptic transmission, cholinergic (GO:0007271), neuromuscular synaptic transmission (GO:0007274), nervous system development (GO:0007399), locomotory behavior (GO:0007626), regulation of acetylcholine secretion, neurotransmission (GO:0014056), monoatomic ion transmembrane transport (GO:0034220), response to nicotine (GO:0035094), behavioral response to nicotine (GO:0035095), regulation of membrane potential (GO:0042391), regulation of dendrite morphogenesis (GO:0048814), membrane depolarization (GO:0051899), excitatory postsynaptic potential (GO:0060079), synaptic transmission involved in micturition (GO:0060084), acetylcholine receptor signaling pathway (GO:0095500), presynaptic modulation of chemical synaptic transmission (GO:0099171), response to acetylcholine (GO:1905144)

GO Molecular Function (8): ligand-gated monoatomic ion channel activity (GO:0015276), acetylcholine receptor activity (GO:0015464), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), acetylcholine binding (GO:0042166), 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 (21): nucleolus (GO:0005730), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), membrane (GO:0016020), nuclear speck (GO:0016607), dendrite (GO:0030425), cation channel complex (GO:0034703), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), neuron projection (GO:0043005), neuronal cell body (GO:0043025), plasma membrane raft (GO:0044853), synapse (GO:0045202), postsynaptic membrane (GO:0045211), ciliary tip (GO:0097542), presynapse (GO:0098793), neurotransmitter receptor complex (GO:0098878), synaptic membrane (GO:0097060)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Presynaptic nicotinic acetylcholine receptors	2
Postsynaptic nicotinic acetylcholine receptors	2
Acetylcholine binding and downstream events	2
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
cellular anatomical structure	5
cytoplasm	3
cilium	3
chemical synaptic transmission	2
postsynaptic neurotransmitter receptor activity	2
endomembrane system	2
intracellular membrane-bounded organelle	2
monoatomic ion channel complex	2
plasma membrane signaling receptor complex	2
transport	1
regulation of muscle contraction	1
smooth muscle contraction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
behavior	1
acetylcholine secretion, neurotransmission	1
regulation of synaptic transmission, cholinergic	1
regulation of neurotransmitter secretion	1
regulation of amine transport	1
monoatomic ion transport	1
transmembrane transport	1
response to chemical	1
adult behavior	1
response to nicotine	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
regulation of anatomical structure morphogenesis	1
dendrite morphogenesis	1
regulation of dendrite development	1
regulation of membrane potential	1
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
neuromuscular synaptic transmission	1
micturition	1
acetylcholine receptor activity	1
postsynaptic signal transduction	1

Protein interactions and networks

STRING

1016 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNA3	PSMA4	P25789	939
CHRNA3	CHRNA5	P30532	855
CHRNA3	CHRNB4	P30926	822
CHRNA3	HYKK	A2RU49	784
CHRNA3	CYP2A6	P00190	777
CHRNA3	FAM13A	O94988	720
CHRNA3	IREB2	P48200	696
CHRNA3	HHIP	Q96QV1	664
CHRNA3	RIC3	Q7Z5B4	662
CHRNA3	CLPTM1L	Q96KA5	620
CHRNA3	GABBR2	O75899	571
CHRNA3	DEGS2	Q6QHC5	570
CHRNA3	CHRM1	P11229	545
CHRNA3	AGER	Q15109	544
CHRNA3	IGBP1	P78318	539

IntAct

15 interactions, top by confidence:

A	B	Type	Score
CHRNA5	CHRNB2	psi-mi:“MI:0914”(association)	0.660
CHRNB2	CHRNA5	psi-mi:“MI:0914”(association)	0.660
LYPD6	CHRNB2	psi-mi:“MI:0914”(association)	0.350
LYNX1	CHRNB2	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
CHRNA3	TMEM223	psi-mi:“MI:0914”(association)	0.350
CLRN2	FAM234B	psi-mi:“MI:0914”(association)	0.350
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DOC2B	POTEF	psi-mi:“MI:0914”(association)	0.350
KLC3	DCTN6	psi-mi:“MI:0914”(association)	0.350
HTR3A	EXTL3	psi-mi:“MI:0914”(association)	0.350
CHRNA3	ENTPD6	psi-mi:“MI:0914”(association)	0.350

BioGRID (64): GLT8D2 (Affinity Capture-MS), TMEM231 (Affinity Capture-MS), EDA (Affinity Capture-MS), GLRB (Affinity Capture-MS), TMEM219 (Affinity Capture-MS), LEMD2 (Affinity Capture-MS), TMEM143 (Affinity Capture-MS), CNNM1 (Affinity Capture-MS), TPST2 (Affinity Capture-MS), ENTPD7 (Affinity Capture-MS), ITPR2 (Affinity Capture-MS), FAM69A (Affinity Capture-MS), TMEM223 (Affinity Capture-MS), MIB1 (Affinity Capture-MS), APOL2 (Affinity Capture-MS)

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

4 interactions.

A	Effect	B	Mechanism
CHRNA3	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta2”	binding
CHRNA3	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta4”	binding
CHRNA3	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta4”	binding
CHRNA3	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta2-beta3”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	11
Uncertain significance	120
Likely benign	45
Benign	19

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
1801723	NM_000743.5(CHRNA3):c.518_519del (p.Cys173fs)	Pathogenic
3492531	NM_000743.5(CHRNA3):c.1103del (p.Lys368fs)	Pathogenic
805847	NM_000743.5(CHRNA3):c.1010_1011del (p.Thr337fs)	Pathogenic
805848	NM_000743.5(CHRNA3):c.1019C>G (p.Ser340Ter)	Pathogenic
805849	NM_000743.5(CHRNA3):c.267+2T>G	Pathogenic
1179064	NM_000743.5(CHRNA3):c.1099C>T (p.Gln367Ter)	Likely pathogenic
3346750	NM_000743.5(CHRNA3):c.518dup (p.Cys173fs)	Likely pathogenic
3577734	NM_000743.5(CHRNA3):c.1304_1305del (p.Ser435fs)	Likely pathogenic
3577748	NM_000743.5(CHRNA3):c.913G>T (p.Gly305Ter)	Likely pathogenic
3577769	NM_000743.5(CHRNA3):c.262A>T (p.Lys88Ter)	Likely pathogenic
3577772	NM_000743.5(CHRNA3):c.223-1G>A	Likely pathogenic
3779526	NM_000743.5(CHRNA3):c.539G>A (p.Trp180Ter)	Likely pathogenic
873308	NM_000743.5(CHRNA3):c.725del (p.Leu242fs)	Likely pathogenic
873309	NM_000743.5(CHRNA3):c.708_709insG (p.Ile237fs)	Likely pathogenic
873310	NM_000743.5(CHRNA3):c.247_248insG (p.Thr83fs)	Likely pathogenic
873311	NM_000743.5(CHRNA3):c.1A>G (p.Met1Val)	Likely pathogenic

SpliceAI

1113 predictions. Top by Δscore:

Variant	Effect	Δscore
15:78593086:TAACA:T	acceptor_loss	1.0000
15:78593088:ACAGG:A	acceptor_loss	1.0000
15:78593089:CAGG:C	acceptor_loss	1.0000
15:78593091:G:A	acceptor_loss	1.0000
15:78601247:CCTTA:C	donor_loss	1.0000
15:78601248:CTTA:C	donor_loss	1.0000
15:78601249:TTA:T	donor_loss	1.0000
15:78601250:TACC:T	donor_loss	1.0000
15:78601251:A:AC	donor_gain	1.0000
15:78601251:ACC:A	donor_loss	1.0000
15:78601252:C:CC	donor_gain	1.0000
15:78601252:C:G	donor_loss	1.0000
15:78601252:CCT:C	donor_gain	1.0000
15:78601413:AT:A	donor_gain	1.0000
15:78602260:CAGCA:C	acceptor_gain	1.0000
15:78602261:AGCA:A	acceptor_gain	1.0000
15:78602262:GCA:G	acceptor_gain	1.0000
15:78602262:GCAC:G	acceptor_loss	1.0000
15:78602263:CA:C	acceptor_gain	1.0000
15:78602263:CAC:C	acceptor_gain	1.0000
15:78602264:ACT:A	acceptor_loss	1.0000
15:78602265:C:CC	acceptor_gain	1.0000
15:78617022:A:AC	donor_gain	1.0000
15:78617023:C:CC	donor_gain	1.0000
15:78617136:C:CT	acceptor_gain	1.0000
15:78617148:C:CT	acceptor_gain	1.0000
15:78617149:A:T	acceptor_gain	1.0000
15:78618613:TTAC:T	donor_loss	1.0000
15:78618615:A:AC	donor_gain	1.0000
15:78618616:C:CT	donor_gain	1.0000

AlphaMissense

3311 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:78596692:C:G	R477P	1.000
15:78617052:A:G	W117R	1.000
15:78617052:A:T	W117R	1.000
15:78617109:A:G	W98R	1.000
15:78617109:A:T	W98R	1.000
15:78596695:T:G	D476A	0.999
15:78596707:G:T	A472D	0.999
15:78596718:C:A	W468C	0.999
15:78596718:C:G	W468C	0.999
15:78596720:A:G	W468R	0.999
15:78596720:A:T	W468R	0.999
15:78601288:C:G	A452P	0.999
15:78601649:T:A	R331S	0.999
15:78601649:T:G	R331S	0.999
15:78601650:C:G	R331T	0.999
15:78601665:A:G	L326P	0.999
15:78601848:A:G	L265P	0.999
15:78601853:G:C	F263L	0.999
15:78601853:G:T	F263L	0.999
15:78601855:A:G	F263L	0.999
15:78601927:G:T	R239S	0.999
15:78602021:C:A	W207C	0.999
15:78602021:C:G	W207C	0.999
15:78602023:A:G	W207R	0.999
15:78602023:A:T	W207R	0.999
15:78602123:A:C	C173W	0.999
15:78602124:C:G	C173S	0.999
15:78602124:C:T	C173Y	0.999
15:78602125:A:G	C173R	0.999
15:78602125:A:T	C173S	0.999

dbSNP variants (sampled 300 via entrez): RS1000108643 (15:78603278 G>A), RS1000222556 (15:78607584 C>A,T), RS1000254362 (15:78598084 G>C), RS1000338303 (15:78608255 A>C), RS1000406683 (15:78617576 G>A), RS1000420597 (15:78622868 G>A), RS1000661299 (15:78600036 T>A,G), RS1000695030 (15:78617917 G>A,C), RS1000725595 (15:78598368 A>G), RS1000841933 (15:78597412 C>T), RS1000874450 (15:78597268 A>C), RS1000990634 (15:78599389 A>G,T), RS1001067910 (15:78603357 G>A), RS1001077093 (15:78613463 C>A,G,T), RS1001187232 (15:78620141 C>T)

Disease associations

OMIM: gene MIM:118503 | disease phenotypes: MIM:191800

GenCC curated gene-disease

Disease	Classification	Inheritance
urinary bladder, atony of	Strong	Autosomal recessive

Mondo (4): urinary bladder, atony of (MONDO:0008630), lung adenocarcinoma (MONDO:0005061), squamous cell carcinoma (MONDO:0005096), amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (2): Amyotrophic lateral sclerosis (Orphanet:803), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

11 total (12 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000011	Neurogenic bladder
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000126	Hydronephrosis
HP:0001278	Orthostatic hypotension
HP:0001508	Failure to thrive
HP:0002020	Gastroesophageal reflux
HP:0012624	Stage 2 chronic kidney disease
HP:0030211	Slow pupillary light response
HP:0007354	Amyotrophic lateral sclerosis

GWAS associations

161 associations (top):

Study	Trait	p-value
GCST000170_1	Lung cancer	5.000000e-20
GCST000171_1	Nicotine dependence	6.000000e-20
GCST000172_1	Lung cancer	3.000000e-18
GCST000233_1	Lung cancer	1.000000e-08
GCST000359_1	Chronic obstructive pulmonary disease	1.000000e-10
GCST000459_3	Lung cancer	3.000000e-26
GCST000506_2	Lung adenocarcinoma	2.000000e-51
GCST000603_3	Chronic obstructive pulmonary disease	2.000000e-08
GCST000666_1	Smoking behavior	3.000000e-73
GCST000668_1	Smoking behavior	2.000000e-66
GCST001251_2	Pulmonary function	5.000000e-07
GCST001321_4	Chronic obstructive pulmonary disease	1.000000e-06
GCST001699_13	Serum albumin levels	6.000000e-07
GCST001762_462	Obesity-related traits	6.000000e-08
GCST001784_10	Pulmonary function (smoking interaction)	9.000000e-08
GCST001784_33	Pulmonary function (smoking interaction)	7.000000e-07
GCST002350_1	Chronic obstructive pulmonary disease (severe)	3.000000e-16
GCST002351_1	Chronic obstructive pulmonary disease (moderate to severe)	6.000000e-14
GCST002525_19	Local histogram emphysema pattern	9.000000e-11
GCST002525_5	Local histogram emphysema pattern	3.000000e-13
GCST002539_77	Schizophrenia	2.000000e-13
GCST002584_1	Exhaled carbon monoxide levels	2.000000e-09
GCST002625_6	Chronic bronchitis and chronic obstructive pulmonary disease	3.000000e-06
GCST002625_8	Chronic bronchitis and chronic obstructive pulmonary disease	2.000000e-08
GCST002795_3	Chronic obstructive pulmonary disease	6.000000e-07
GCST002798_1	Pulmonary artery enlargement and chronic obstructive pulmonary disease	7.000000e-10
GCST002945_47	Emphysema imaging phenotypes	2.000000e-09
GCST003185_2	Nicotine dependence	4.000000e-17
GCST003262_1161	Post bronchodilator FEV1	3.000000e-06
GCST003262_131	Post bronchodilator FEV1	2.000000e-07

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0005109	energy expenditure
EFO:0004713	FEV/FVC ratio
EFO:0005850	emphysema pattern measurement
EFO:0006520	carbon monoxide exhalation measurement
EFO:0006347	pulmonary artery enlargement
EFO:0007626	emphysema imaging measurement
EFO:0007796	parental longevity
EFO:0007813	cotinine measurement
EFO:0006953	family history of lung cancer
EFO:0006525	cigarettes per day measurement
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0010078	dentures
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009762	healthspan
EFO:0006527	smoking status measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (13): CHEMBL1907594 (PROTEIN COMPLEX), CHEMBL2109233 (PROTEIN COMPLEX), CHEMBL2109234 (PROTEIN COMPLEX), CHEMBL2111384 (PROTEIN COMPLEX GROUP), CHEMBL2221346 (PROTEIN COMPLEX GROUP), CHEMBL3068 (SINGLE PROTEIN), CHEMBL3137272 (PROTEIN COMPLEX), CHEMBL3137273 (PROTEIN COMPLEX), CHEMBL3137285 (PROTEIN COMPLEX), CHEMBL3885595 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 426,590 (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
CHEMBL1076903	VARENICLINE	4	5,807
CHEMBL267936	MECAMYLAMINE	4	5,623
CHEMBL3	NICOTINE	4	184,969
CHEMBL46	ONDANSETRON	4	41,386
CHEMBL56564	TROPISETRON	4	19,312
CHEMBL667	ACETYLCHOLINE	4	124,626
CHEMBL894	BUPROPION	4	36,982
CHEMBL289469	GRANISETRON	4	431
CHEMBL2103881	DEXMECAMYLAMINE	3	18
CHEMBL497939	CYTISINICLINE	3	2,766
CHEMBL111659	ALTINICLINE	2	129
CHEMBL1172928	RADAFAXINE	2	1,079
CHEMBL1230982	ANABASEINE	2	139
CHEMBL1257065	STILONIUM IODIDE	2	751
CHEMBL132966	RIVANICLINE	2	911
CHEMBL134713	GTS-21	2	269
CHEMBL2179529	AZD1446	2	78
CHEMBL238465	SOFINICLINE	2	153
CHEMBL430497	TEBANICLINE	2	1,155
CHEMBL607048	18-METHOXYCORONARIDINE	2	6
CHEMBL504652	TC-2216	1

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

PharmGKB clinical annotations

17 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1051730	Toxicity	3	Opium alkaloids and derivatives	Pain
rs1051730	Other	3	ethanol	Alcohol abuse
rs1051730	Dosage	3	Drugs used in nicotine dependence;nicotine	Tobacco Use Disorder
rs1051730	Efficacy	3	Drugs used in nicotine dependence;nicotine	Tobacco Use Disorder
rs1051730	Other	3	nicotine	Pregnancy
rs1051730	Other	3	Drugs used in nicotine dependence;nicotine	Tobacco Use Disorder
rs1051730	Toxicity	3	nicotine
rs1051730	Toxicity	3	nicotine	Tobacco Use Disorder
rs1051730	Dosage	3	nicotine	Tobacco Use Disorder
rs16969968	Dosage,Efficacy	3	nicotine
rs16969968	Toxicity	3	cocaine	Cocaine dependence
rs3743075	Toxicity	3	nicotine	Tobacco Use Disorder
rs3743078	Toxicity	3	nicotine	Tobacco Use Disorder
rs578776	Other	3	ethanol	Alcohol abuse
rs578776	Efficacy,Toxicity	3	nicotine	Tobacco Use Disorder
rs578776	Toxicity	3	nicotine
rs7170068	Metabolism/PK	3	cotinine	Tobacco Use Disorder

PharmGKB variants

12 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs578776	CHRNA3, CHRNA5	3	3.25	3	ethanol;nicotine
rs615470	CHRNA3, CHRNA5	3	0.50	1	ethanol
rs660652	CHRNA3, CHRNA5	3	2.25	1	nicotine;Opium alkaloids and derivatives
rs1051730	CHRNA3	3	3.00	9	Drugs used in nicotine dependence;nicotine;nicotine;Opium alkaloids and derivatives;ethanol
rs3743078	CHRNA3	3	2.00	1	nicotine
rs7170068	CHRNA3	3	0.00	1	cotinine
rs16969968	CHRNA3, CHRNA5	2B	11.50	7	cotinine;bupropion;Drugs used in nicotine dependence;nicotine;varenicline;nicotine;ethanol;Opium alkaloids and derivatives;cocaine
rs3743075	CHRNA3	3	3.00	1	nicotine
rs3743074	CHRNA3		0.00	0
rs6495307	CHRNA3		0.00	0
rs3743077	CHRNA3		0.00	0
rs2869546	CHRNA3		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 (6 total), top 6:

Ligand	Action	Affinity	Parameter
[125I]epibatidine	Full agonist	11.15	pKd
[3H]epibatidine	Full agonist	11.15	pKd
atracurium	Antagonist	9.05	pIC50
varenicline	Agonist	7.4	pKi
nicotine	Agonist	5.76	pKi
mecamylamine	Channel blocker	5.12	pIC50

Binding affinities (BindingDB)

21 measured of 38 human assays (44 total across all organisms); most potent 21 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
6-[5-(7-Aza-bicyclo[2.2.1]hept-2-yl)-pyridin-3-yl]-hex-5-yn-1-ol	KI	0.23 nM
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM
CHEMBL4453542	KI	2.5 nM
CHEMBL4450133	KI	6.7 nM
3-(3-Methyl-isoxazol-5-ylmethylene)-1-aza-bicyclo[2.2.1]heptane	IC50	14 nM
3-[1-(3-Methyl-isoxazol-5-yl)-meth-(Z)-ylidene]-1-aza-bicyclo[2.2.1]heptane	IC50	15 nM
CHEMBL4440403	KI	20 nM
CHEMBL3329540	EC50	53 nM
CHEMBL4535466	KI	138 nM
CHEMBL3329544	KI	310 nM
CHEMBL3329545	EC50	540 nM
CHEMBL4463888	KI	631 nM
18-methoxycoronaridine	KI	700 nM
3-[1-(3-Methyl-isoxazol-5-yl)-meth-(E)-ylidene]-1-aza-bicyclo[2.2.2]octane	IC50	854 nM
CHEMBL4468230	KI	1630 nM
CHEMBL4515416	EC50	2860 nM
Dihydro-Beta-erythroidine	KI	5090 nM
SSR591813	KI	6000 nM
CHEMBL4550498	EC50	6320 nM
NSC_123990	KI	8750 nM
CHEMBL4475133	EC50	65500 nM

ChEMBL bioactivities

1274 potent at pChembl≥5 of 1588 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	Kd	0.03	nM	EPIBATIDINE
10.46	Ki	0.035	nM	EPIBATIDINE
9.90	Ki	0.126	nM	CHEMBL1209244
9.83	Ki	0.149	nM	CHEMBL1209243
9.82	Ki	0.15	nM	EPIBATIDINE
9.82	Ki	0.15	nM	(-)-EPIBATIDINE
9.80	Ki	0.16	nM	CHEMBL220476
9.80	IC50	0.16	nM	CHEMBL1269126
9.80	Ki	0.158	nM	CHEMBL1209187
9.80	EC50	0.16	nM	CHEMBL1209244
9.73	Ki	0.186	nM	CHEMBL1209124
9.72	Ki	0.191	nM	EPIBATIDINE
9.70	Ki	0.2	nM	CHEMBL462846
9.70	IC50	0.2	nM	CHEMBL4869892
9.66	Ki	0.22	nM	EPIBATIDINE
9.64	Ki	0.23	nM	CHEMBL366991
9.64	Ki	0.23	nM	EPIBATIDINE
9.62	IC50	0.24	nM	CHEMBL4860756
9.61	Ki	0.243	nM	CHEMBL1209187
9.55	IC50	0.28	nM	CHEMBL4876825
9.52	Kd	0.3	nM	EPIBATIDINE
9.52	IC50	0.3	nM	CHEMBL412032
9.52	Kd	0.3	nM	(-)-EPIBATIDINE
9.46	IC50	0.35	nM	CHEMBL4462550
9.43	IC50	0.37	nM	CHEMBL4454232
9.42	Ki	0.38	nM	CHEMBL2024096
9.42	Ki	0.382	nM	CHEMBL1209186
9.39	IC50	0.41	nM	CHEMBL4878931
9.34	IC50	0.46	nM	CHEMBL4556075
9.34	Ki	0.457	nM	EPIBATIDINE
9.30	IC50	0.5	nM	CHEMBL595311
9.29	IC50	0.51	nM	CHEMBL566208
9.28	Ki	0.527	nM	HOMOEPIBATIDINE
9.26	IC50	0.55	nM	CHEMBL4443845
9.24	IC50	0.57	nM	CHEMBL4585225
9.24	IC50	0.58	nM	CHEMBL566886
9.21	IC50	0.62	nM	CHEMBL566050
9.19	IC50	0.65	nM	CHEMBL4463134
9.19	IC50	0.65	nM	CHEMBL565844
9.16	Ki	0.684	nM	CHEMBL4163848
9.15	IC50	0.7	nM	CHEMBL569465
9.13	Ki	0.748	nM	CHEMBL1209124
9.12	IC50	0.75	nM	CHEMBL429557
9.10	Ki	0.799	nM	CHEMBL4170527
9.09	Ki	0.818	nM	CHEMBL4163257
9.07	Ki	0.856	nM	CHEMBL1209126
9.05	Ki	0.882	nM	CHEMBL1209072
9.04	IC50	0.92	nM	CHEMBL4531333
9.03	Ki	0.944	nM	CHEMBL363973
9.03	Ki	0.925	nM	HOMOEPIBATIDINE

PubChem BioAssay actives

1192 with measured affinity, of 2983 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-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	238148: Dissociation constant against Nicotinic acetylcholine receptor alpha3-beta2	kd	<0.0001	uM
N-[5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-3-pyridinyl]ethanesulfonamide;hydrochloride	495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells	ki	0.0001	uM
N-[5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-3-pyridinyl]propane-2-sulfonamide;hydrochloride	495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells	ki	0.0001	uM
(1R,2R,4S)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	1563867: Displacement of [3H]epibatidine from human alpha3beta4 nAChR transfected in HEK243 cell membrane	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
6-[5-(7-azabicyclo[2.2.1]heptan-2-yl)-3-pyridinyl]hex-5-yn-1-ol	239326: Inhibition of [3H]epibatidine binding to Nicotinic acetylcholine receptor alpha3-beta2	ki	0.0002	uM
7-(6-chloro-3-pyridinyl)-2-azabicyclo[2.2.1]heptane	276250: Displacement of [3H]epibatidine from human recombinant alpha-3-beta-4 nAChR in HEK293 cells by SPA assay	ki	0.0002	uM
3-(6-chloro-3-pyridinyl)-3,6-diazabicyclo[3.1.1]heptane	1252850: Displacement of [3H]-Epibatidine from human aplha3beta4 nAChR expressed in HEK293 cells pre-incubated for 5 mins followed by overnight incubation by radioligand liquid scintillation counter analysis	ki	0.0002	uM
(2S)-N-[3-[4-(3-aminopropylamino)butylamino]propyl]-3-cyclohexyl-2-[(2-naphthalen-1-ylacetyl)amino]propanamide	1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay	ic50	0.0002	uM
5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]pyridin-3-ol;hydrochloride	495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells	ki	0.0002	uM
N-[5-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-3-pyridinyl]methanesulfonamide;hydrochloride	495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells	ki	0.0002	uM
(2S)-N-[3-[4-(3-aminopropylamino)butylamino]propyl]-3-cyclohexyl-2-[[(E)-3-phenylprop-2-enoyl]amino]propanamide	1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay	ic50	0.0003	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
(3S)-3-[[(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-sulfanylpropanoyl]amino]propanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoyl]amino]-4-[[(2S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	241632: Inhibitory concentration against Nicotinic acetylcholine receptor alpha3-beta2	ic50	0.0003	uM
N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-cyclohexyl-1-oxopropan-2-yl]benzamide	1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay	ic50	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
N-[3-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]-4-pyridinyl]methanesulfonamide;hydrochloride	495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells	ki	0.0004	uM
N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]cyclohexanecarboxamide	1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay	ic50	0.0005	uM
6-(6-chloro-3-pyridinyl)-8-azabicyclo[3.2.1]octane	276250: Displacement of [3H]epibatidine from human recombinant alpha-3-beta-4 nAChR in HEK293 cells by SPA assay	ki	0.0005	uM
2-(tert-butylamino)-1-(3,4-dichlorophenyl)butan-1-one	459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0005	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	450496: Inhibition of alpha3beta2 nAChR	ic50	0.0005	uM
N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-cyclohexyl-1-oxopropan-2-yl]cycloheptanecarboxamide	1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay	ic50	0.0006	uM
N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-cyclohexyl-1-oxopropan-2-yl]cyclopentanecarboxamide	1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay	ic50	0.0006	uM
N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]cyclopentanecarboxamide	1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay	ic50	0.0006	uM
2-(tert-butylamino)-1-(3-chlorophenyl)butan-1-one	459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0006	uM
2-(tert-butylamino)-1-(3-chloro-4-methylphenyl)propan-1-one	459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0006	uM
2-(tert-butylamino)-1-(3,4-dichlorophenyl)pentan-1-one	459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0006	uM
5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-N-(4-nitrophenyl)pyridin-3-amine	1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes	ki	0.0007	uM
2-(tert-butylamino)-1-(3-chlorophenyl)pentan-1-one	459714: Antagonist activity at alpha3beta4 nAChR receptor in human SH-SY5Y cells assessed as inhibition of carbamylcholine-induced 86Rb+ efflux by liquid scintillation counting	ic50	0.0007	uM
5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-N-phenylpyridin-3-amine	1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes	ki	0.0008	uM
5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-N-[4-(trifluoromethyl)phenyl]pyridin-2-amine	1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes	ki	0.0008	uM
(3S)-3-[[(2S)-1-[(2S)-4-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-3-sulfanylpropanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-3-hydroxybutanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-4-oxo-4-[[(2R)-1-oxo-3-sulfanylpropan-2-yl]amino]butanoic acid	242182: Inhibitory concentration against Nicotinic acetylcholine receptor alpha3-beta2; Range is 0.3-1.5 nM	ic50	0.0008	uM
5-(6-chloro-3-pyridinyl)-2-azabicyclo[2.2.1]heptane	276250: Displacement of [3H]epibatidine from human recombinant alpha-3-beta-4 nAChR in HEK293 cells by SPA assay	ki	0.0009	uM
N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-1-oxo-3-phenylpropan-2-yl]butanamide	1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay	ic50	0.0009	uM
(2S)-N-[3-[4-(3-aminopropylamino)butylamino]propyl]-2-[[2-(2-bicyclo[2.2.1]heptanyl)acetyl]amino]-3-cyclohexylpropanamide	1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay	ic50	0.0009	uM
N-[(2S)-1-[3-[[(1R,2R)-2-[(3-aminopropylamino)methyl]cyclopropyl]methylamino]propylamino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]butanamide	1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay	ic50	0.0009	uM
(1R,5R,6S)-6-[2-(4-methoxy-3-pyridinyl)phenoxy]-3-azabicyclo[3.2.1]octane;hydrochloride	495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells	ki	0.0009	uM
(1R,5R,6S)-6-[2-(4-fluoro-3-pyridinyl)phenoxy]-3-azabicyclo[3.2.1]octane;hydrochloride	495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells	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
4-[[5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-3-pyridinyl]amino]phenol	1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes	ki	0.0010	uM
5-(3,6-diazabicyclo[3.1.1]heptan-3-yl)-N-[4-(trifluoromethyl)phenyl]pyridin-3-amine	1359525: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in HEK293 cell membranes	ki	0.0010	uM
(1R,15R,17S,18S)-17-ethyl-7-methoxy-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4(9),5,7-tetraene	1973135: Displacement of [3H]Ibogaine from human alpha3beta4 nAChRs expressed in HEK293 cells assessed as inhibition constant incubated for 2 hrs by scintillation counter analysis	ki	0.0010	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	242122: Inhibitory concentration against Nicotinic acetylcholine receptor alpha3-beta4; Range is 0.7-1 nM	ic50	0.0010	uM
3-[2-[[(1R,5R,6S)-3-azabicyclo[3.2.1]octan-6-yl]oxy]phenyl]pyridin-4-amine;hydrochloride	495033: Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells	ki	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
N-[(2S)-1-[3-[4-(3-aminopropylamino)butylamino]propylamino]-3-cyclohexyl-1-oxopropan-2-yl]cyclobutanecarboxamide	1563140: Antagonist activity at alpha3beta4 nAChR (unknown origin) expressed in Xenopus laevis oocytes assessed as inhibition of Ach-induced channel activation at -100 mV holding potential treated for 1 min by two electrode voltage-clamp assay	ic50	0.0011	uM
(2S)-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]-N-[(2S)-1-[[(2S,3S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]pentanediamide	241632: Inhibitory concentration against Nicotinic acetylcholine receptor alpha3-beta2	ic50	0.0011	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	450496: Inhibition of alpha3beta2 nAChR	ic50	0.0011	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, increases expression	7
Acetylcholine	increases activity, affects activity, affects binding, decreases reaction, increases reaction	6
Nicotine	affects binding, increases activity, affects reaction, increases expression, decreases expression	4
epibatidine	affects binding, decreases reaction, increases activity	3
N’-nitrosonornicotine	affects binding	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects reaction, increases expression	2
Tubocurarine	affects binding, decreases reaction, increases activity	2
Aflatoxin B1	increases expression	2
aristolochic acid I	increases expression	1
triptolide	affects binding, decreases reaction, increases activity	1
cytisine	affects binding, increases activity	1
propionaldehyde	increases expression	1
bisphenol A	affects activity, affects binding, decreases reaction, increases reaction	1
decabromobiphenyl ether	increases expression	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
tetrachlorodian	increases expression	1
4-nonylphenol	affects activity, affects binding, decreases reaction, increases reaction	1
pentanal	increases expression	1
celastrol	affects binding, decreases reaction, increases activity	1
4-octylphenol	affects activity, affects binding, decreases reaction	1
imidacloprid	affects binding, increases activity	1
cisatracurium	affects binding, decreases reaction, increases activity	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1

ChEMBL screening assays

436 unique, capped per target: 343 binding, 91 functional, 2 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009284	Functional	Agonist activity at alpha3beta4 nAChR expressed in HEK293 cells at 1 mM by FLIPR membrane potential assay	Carbamoylcholine analogs as nicotinic acetylcholine receptor agonists–structural modifications of 3-(dimethylamino)butyl dimethylcarbamate (DMABC). — Bioorg Med Chem Lett
CHEMBL1020767	Binding	Displacement of [3H]epibatidine from alpha3beta4 nAChR expressed in HEK293 cells	Carbamoylcholine analogs as nicotinic acetylcholine receptor agonists–structural modifications of 3-(dimethylamino)butyl dimethylcarbamate (DMABC). — Bioorg Med Chem Lett
CHEMBL4603065	ADMET	Inhibition of human alpha3beta4 nAChR assessed as increase in acetylcholine-induced normalized current at 2 uM (Rvb = 78.5 +/- 10 uM)	Differentiating the Pharmacodynamics and Toxicology of Macrolide and Ketolide Antibiotics. — 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_D1KF	PrecisION hnAChR alpha3/beta4-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT00868088	PHASE4	COMPLETED	Photodynamic Therapy to Treat Actinic Damage in Patients With Squamous Cell Carcinoma (SCC) of the Lip
NCT02088515	PHASE4	COMPLETED	Nedaplatin (Jiebaishu®) Combined With Docetaxel for Advanced Lung Squamous Cell Carcinoma
NCT02151149	PHASE4	COMPLETED	Safety and Efficacy Study of Abraxane in Combination With Carboplatin to Treat Advanced NSCL Cancer in the Elderly
NCT03388931	PHASE4	WITHDRAWN	Radiotherapy Dose Escalation in Locally Advanced Squamous Cell Carcinoma of the Larynx or Hypopharynx
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)
NCT06031246	PHASE3	RECRUITING	Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018)
NCT06634966	PHASE3	RECRUITING	Segmentectomy for Solid-dominant Lung Cancer
NCT07169903	PHASE3	NOT_YET_RECRUITING	Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT
NCT07481786	PHASE3	RECRUITING	Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
NCT00101582	PHASE3	COMPLETED	Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer
NCT00201279	PHASE3	COMPLETED	Chemoprevention Study of Oral Cavity Squamous Cell Carcinoma
NCT00201383	PHASE3	COMPLETED	Post-Operative Adjuvant Concurrent Chemoradiotherapy For High Risk Oral Cavity Squamous Cell Carcinoma Patients
NCT00382031	PHASE3	COMPLETED	Zalutumumab in Patients With Non-curable Head and Neck Cancer
NCT00472459	PHASE3	COMPLETED	Photodynamic Therapy (PDT) With Metvix® 160 Milligrams/Gram Cream in Organ Transplant Participants With Non-melanoma Skin Cancer
NCT00559351	PHASE3	TERMINATED	RCT on the Combined Modality Treatment of Squamous Cell Carcinoma of the Esophagus
NCT01161498	PHASE3	TERMINATED	Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer
NCT01363466	PHASE3	TERMINATED	Evaluation of Hysterectomy After Chemoradiation Therapy for Stage IB2/II Cervical Cancer
NCT01532453	PHASE3	TERMINATED	Prevention of UV-induced Carcinogenic Skin Alterations in Immunosuppressed Solid Organ Transplanted Patients
NCT01706939	PHASE3	ACTIVE_NOT_RECRUITING	The Quarterback Trial: Reduced Dose Radiotherapy for HPV+ Oropharynx Cancer
NCT03115476	PHASE3	TERMINATED	A Trial to Compare the Incidence of Squamous Cell Carcinoma (SCC) and Other Skin Neoplasia on Skin Areas Treated With Ingenol Disoxate Gel or Vehicle Gel for Actinic Keratosis on Face and Chest or Scalp
NCT03257267	PHASE3	COMPLETED	Study of Cemiplimab in Adults With Cervical Cancer
NCT00040794	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer
NCT00087412	PHASE2	COMPLETED	S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer
NCT00118144	PHASE2	COMPLETED	Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer
NCT00118183	PHASE2	COMPLETED	Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer