CHRM3

Summary

CHRM3 (cholinergic receptor muscarinic 3, HGNC:1952) is a protein-coding gene on chromosome 1q43, encoding Muscarinic acetylcholine receptor M3 (P20309). The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins.

The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The muscarinic cholinergic receptor 3 controls smooth muscle contraction and its stimulation causes secretion of glandular tissue. Alternative promoter use and alternative splicing results in multiple transcript variants that have different tissue specificities.

Source: NCBI Gene 1131 — RefSeq curated summary.

At a glance

• Gene–disease (curated): prune belly syndrome (Strong, GenCC)
• GWAS associations: 26
• Clinical variants (ClinVar): 177 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 40
• Druggable target: yes — 207 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001375978

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1952
Approved symbol	CHRM3
Name	cholinergic receptor muscarinic 3
Location	1q43
Locus type	gene with protein product
Status	Approved
Aliases	m3AChR
Ensembl gene	ENSG00000133019
Ensembl biotype	protein_coding
OMIM	118494
Entrez	1131

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 31 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000255380, ENST00000448020, ENST00000468573, ENST00000481779, ENST00000487470, ENST00000492335, ENST00000615928, ENST00000674678, ENST00000675184, ENST00000675709, ENST00000676153, ENST00000676433, ENST00000875837, ENST00000875838, ENST00000875839, ENST00000875840, ENST00000875841, ENST00000875842, ENST00000875843, ENST00000875844, ENST00000875845, ENST00000875846, ENST00000875847, ENST00000928260, ENST00000928261, ENST00000928262, ENST00000928263, ENST00000928264, ENST00000928265, ENST00000928266, ENST00000928267, ENST00000928268, ENST00000948992, ENST00000948993, ENST00000948994, ENST00000948995

RefSeq mRNA: 10 — MANE Select: NM_001375978 NM_000740, NM_001347716, NM_001375978, NM_001375979, NM_001375980, NM_001375981, NM_001375982, NM_001375983, NM_001375984, NM_001375985

CCDS: CCDS1616

Canonical transcript exons

ENST00000676153 — 7 exons

Exon	Start	End
ENSE00001442054	239827252	239827378
ENSE00001442055	239678186	239678288
ENSE00001442056	239632224	239632286
ENSE00001868626	239492709	239492807
ENSE00001923821	239545641	239545749
ENSE00003899691	239386568	239387227
ENSE00003902309	239907433	239915450

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 99.19.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1964 / max 200.9506, expressed in 510 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9313	1.3611	241
9315	0.6775	187
9319	0.4048	114
9317	0.1989	91
9314	0.1314	65
9318	0.1136	59
9321	0.1069	60
9316	0.1058	51
9324	0.0474	27
9320	0.0229	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.19	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.90	gold quality
middle temporal gyrus	UBERON:0002771	98.76	gold quality
parotid gland	UBERON:0001831	98.72	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.01	gold quality
postcentral gyrus	UBERON:0002581	93.26	gold quality
superior frontal gyrus	UBERON:0002661	93.26	gold quality
parietal lobe	UBERON:0001872	92.94	gold quality
entorhinal cortex	UBERON:0002728	92.03	gold quality
orbitofrontal cortex	UBERON:0004167	90.99	gold quality
primary visual cortex	UBERON:0002436	88.79	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.69	gold quality
occipital lobe	UBERON:0002021	88.13	gold quality
frontal pole	UBERON:0002795	86.96	gold quality
buccal mucosa cell	CL:0002336	86.55	gold quality
palpebral conjunctiva	UBERON:0001812	86.10	gold quality
cardia of stomach	UBERON:0001162	85.48	gold quality
Brodmann (1909) area 10	UBERON:0013541	84.79	gold quality
seminal vesicle	UBERON:0000998	83.69	gold quality
frontal cortex	UBERON:0001870	82.52	gold quality
prefrontal cortex	UBERON:0000451	82.14	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.14	gold quality
neocortex	UBERON:0001950	80.83	gold quality
body of pancreas	UBERON:0001150	80.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.44	gold quality
lower esophagus	UBERON:0013473	80.43	gold quality
cerebral cortex	UBERON:0000956	80.34	gold quality
eye	UBERON:0000970	80.21	gold quality
pons	UBERON:0000988	79.66	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	159.46
E-ENAD-27	yes	125.85
E-GEOD-83139	yes	110.74
E-HCAD-35	yes	102.62
E-HCAD-25	yes	79.45
E-CURD-119	yes	31.80
E-ANND-3	yes	13.51
E-GEOD-81608	yes	12.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting CHRM3, 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-5193	100.00	67.26	1744
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-4507	99.14	65.27	515
HSA-MIR-3940-5P	99.14	65.26	493
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-134-3P	96.83	66.22	1001
HSA-MIR-6861-5P	96.23	67.19	800

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• potential role of endogenous GRK6 in the regulation of M(3) mACh receptor (PMID:11856737)
• Stimulation of phospholipase C-epsilon by the M3 muscarinic acetylcholine receptor mediated by cyclic AMP and the GTPase Rap2B (PMID:11877431)
• We show that activation of these receptors leads to divergent growth responses: M(2) AChR activation causes an increase in DNA synthesis, whereas M(3) AChR activation causes a dramatic decrease in DNA synthesis. (PMID:12126481)
• both G(q) and G(11) are involved in mediating the action of the M(3) receptor on cytosolic Ca(2+) in HT29 cells (PMID:12194018)
• Single nucleotide polymorphisms not more frequent in asthma. No nonrandom transmission of short tandem repeat polymorphism haplotypes in asthma. Nonrandom transmission of haplotypes in skin test reactivity to cockroach allergens. (PMID:12642833)
• the conserved poly-basic region in the C-terminal tail of the M3 muscarinic receptor contributes to the ability to mediate protection against apoptotic cell death (PMID:12649280)
• the M3 receptor displays a major ARF1-dependent route of phospholipase D1 activation with an additional ARF6-dependent pathway to PLD1 or PLD2 (PMID:12799371)
• M3 mAChR desensitization is mediated by GRK6 in human SH-SY5Y cells, and receptor desensitization of phospholipase C signaling can be monitored in ‘real-time’ in single, living cells. (PMID:14573754)
• The muscarinic acetylcholine receptor M3 is a mediator of bradycardia and bronchoconstriction due to vagal innervation. (PMID:14977875)
• M3 up-regulates “sedentary” integrins alpha2beta1 and alpha3beta1. Inhibition of migration by M3 was mediated through Ca2+-dependent guanylyl cyclase-cyclic GMP-protein kinase G signaling pathway. (PMID:15263021)
• (HEK) 293 cells expressing recombinant Galpha(q/11)-coupled muscarinic M3 receptors showed transient coexpression of RGS proteins (PMID:15383626)
• demonstration of the antigenicity of a novel peptide fragment of the human muscarinic acetylcholine receptor 3 in primary Sjogren’s syndrome (PMID:15725576)
• binding of beta-arrestin-1 to muscarinic M(3) receptors requires paired stimulation of two receptor components within the same receptor dimer (PMID:15769745)
• characterization of the muscarinic receptor in the spontaneously immortalized human keratinocyte cell line HaCaT and its role in cell migration (PMID:16113538)
• Data demonstrate that M(1), M(2), and M(3) muscarinic acetylcholine receptors (mAChR)can form homo- and heterodimers in living cells, and suggest that heterodimerization plays a role in the mechanism of mAChR long term regulation. (PMID:16368694)
• The muscarinic Ca2+ signaling pathway is not necessarily affected by depolarization and suggest that the M3 receptor itself is not sensitive to voltage. (PMID:17005862)
• C allele as associated with a reduced acute insulin response and modestly associated with increased risk of early-onset type 2 diabetes in Pima Indians. (PMID:17130513)
• affects endocrine and exocrine hormone and salivary secretion (PMID:17192665)
• Resuts show that urothelium carries multiple cholinergic receptor subtypes, with predominant expression of M2R, M3R and alpha7-nAChR and suggest that this layer-specific distribution serves to stratify cholinergic regulation of urothelial function. (PMID:17335853)
• alphaM3 belongs to a complex and diverse set of synchronously moving parts that change structure relatively late in the channel-opening process. (PMID:17513382)
• M3R was involved in the up-regulation of H1R by activating H1R gene transcription through a PKC-dependent process (PMID:17637176)
• Poly I:C caused increased M3R in airway smooth muscle cells by interacting with TLR3. (PMID:17851256)
• These results indicate caveolae and caveolin-1 facilitate Ca(2+) mobilization leading to ASM contraction induced by submaximal concentrations of acetylcholine. (PMID:17890325)
• the M(3)/M(5) subtypes appear to be the major contributor, leading to intracellular calcium mobilization from the internal store via an IP(3)-dependent pathway in the undifferentiated retinoblastoma cells. (PMID:17951979)
• M3 employs two distinct mechanisms of chemical imitation to potently sequester chemokines, thereby inhibiting chemokine receptor binding events as well as the formation of chemotactic gradients necessary for directed leukocyte trafficking (PMID:18070938)
• Neither the linear M3R peptide nor M3R transfectants represent suitable tools for discrimination of pathogenic from natural autoantibodies in Sjogren’s syndrome. (PMID:18249005)
• The observed effect of tau protein on neurons (in neuroblastomas and primary cultures of hippocampal and cortical neurons) is through M1 and M3 muscarinic receptors. (PMID:18272392)
• The results demonstrate that multiple muscarinic receptor subtypes regulate mTOR, and that both MAPK-dependent and -independent mechanisms may mediate the response in a cell context-specific manner. (PMID:18348264)
• Results demonstrate that the actions of pilocarpine and carbachol in salivary cells are mediated through two distinct signaling mechanisms via M3/M1 receptors. (PMID:18385290)
• Muscarinic receptor M3 expression is associated with invasive migration of melanomas. (PMID:18422974)
• airway M(2)Rs inhibit BK channels by a dual, Gbetagamma-mediated mechanism, a direct membrane-delimited interaction, and the activation of the phospholipase C/protein kinase C pathway (PMID:18524769)
• M2 and M3 receptors are upregulated in a time-dependent and pressure-dependent fashion after as little as a 24 h exposure to increased hydrostatic pressure in bladder (PMID:18563417)
• the beta2 adrenergic and M3 muscarinic receptors, enter cells constitutively by clathrin-independent endocytosis and colocalize with markers of this endosomal pathway on recycling tubular endosomes subsequently recycle back to the plasma membrane (PMID:19033440)
• The DEP domain of RGS7 can directly bind to the third intracellular loop of the M3R and attenuate receptor-induced Ca2+ mobilization in a M3 subtype-selective manner. (PMID:19182865)
• muscarinic M3 receptor stimulation augments cigarette smoke extract-induced IL-8 (but not IL-6) production by airway smooth muscle (PMID:19460789)
• Data show that NALCN and M3R belong to the same protein complex, involving the intracellular I-II loop of NALCN and the intracellular i3 loop of M3R. (PMID:19575010)
• M(3)-muscarinic receptor can regulate the apoptotic properties of a chemotherapeutic DNA-damaging agent by regulating the expression, subcellular trafficking and modification of p53 in a manner that is, in part, dependent on the cell type. (PMID:19648965)
• The protein and gene expression of the M3 receptor in the prostatic carcinoma group were higher than that of benign prostatic hyperplasia group and normal prostate group. (PMID:19668880)
• Data show that exon-acquisition and alternative splicing events of CHRM3 genes were occurred through the continuous integration of transposable elements following conservation. (PMID:19669628)
• m3 receptor-expressing HeLa cells are a valuable system for studying IP(3) receptor ERAD, and suggest that the SPFH1/2 complex is a factor that selectively mediates the ERAD of activated IP(3) receptors. (PMID:19751772)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrm3a	ENSDARG00000071091
danio_rerio	chrm3b	ENSDARG00000071298
mus_musculus	Chrm3	ENSMUSG00000046159
rattus_norvegicus	Chrm3	ENSRNOG00000049410

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), GPR84 (ENSG00000139572), GPR161 (ENSG00000143147), TAAR2 (ENSG00000146378), TAAR6 (ENSG00000146383), TAAR8 (ENSG00000146385), TAAR1 (ENSG00000146399), DRD3 (ENSG00000151577), HTR4 (ENSG00000164270), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), HTR1D (ENSG00000179546), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

Muscarinic acetylcholine receptor M3 — P20309 (reviewed: P20309)

All UniProt accessions (3): A0A6Q8PG67, B1AN12, P20309

UniProt curated annotations — full annotation on UniProt →

Function. The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.

Subunit / interactions. Homodimer; the dimers can form tetramers. Interacts with NALCN. Interacts with TMEM147.

Subcellular location. Cell membrane. Postsynaptic cell membrane. Basolateral cell membrane. Endoplasmic reticulum membrane.

Disease relevance. Prune belly syndrome (PBS) [MIM:100100] A syndrome characterized by thin abdominal musculature with overlying lax skin, cryptorchism, megacystis with disorganized detrusor muscle, and urinary tract abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM3 sub-subfamily.

RefSeq proteins (10): NP_000731, NP_001334645, NP_001362907, NP_001362908, NP_001362909, NP_001362910, NP_001362911, NP_001362912, NP_001362913, NP_001362914 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000995	Musac_Ach_rcpt	Family
IPR001183	Musac_Ach_M3_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (58 total): helix 15, topological domain 8, transmembrane region 7, mutagenesis site 6, glycosylation site 5, strand 5, disulfide bond 2, sequence variant 2, turn 2, chain 1, region of interest 1, short sequence motif 1, compositionally biased region 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8EA0	ELECTRON MICROSCOPY	2.56
8E9W	ELECTRON MICROSCOPY	2.69
8E9Z	ELECTRON MICROSCOPY	2.69
8E9Y	ELECTRON MICROSCOPY	2.79
2CSA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20309-F1	67.30	0.33

Antibody-complex structures (SAbDab): 3 — 8E9W, 8E9Y, 8E9Z

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): 385

Disulfide bonds (2): 141–221, 517–520

Glycosylation sites (5): 5, 6, 15, 41, 48

Mutagenesis-validated functional residues (6):

Position	Phenotype
276	loss of basolateral sorting.
276	loss of basolateral sorting. no effect on basolateral sorting; when associated with l-280 and l-281.
280	loss of basolateral sorting.
280	no effect on basolateral sorting.
281	loss of basolateral sorting.
281	no effect on basolateral sorting.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-390648	Muscarinic acetylcholine receptors
R-HSA-399997	Acetylcholine regulates insulin secretion
R-HSA-416476	G alpha (q) signalling events
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-163685	Integration of energy metabolism
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375280	Amine ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-422356	Regulation of insulin secretion
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 273 (showing top): GOBP_DIGESTION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_274, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CHANDRAN_METASTASIS_DN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, SREBP1_02, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CONTRACTION, MODULE_75, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_MUSCLE_CONTRACTION

GO Biological Process (18): smooth muscle contraction (GO:0006939), regulation of smooth muscle contraction (GO:0006940), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway (GO:0007197), phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway (GO:0007207), G protein-coupled acetylcholine receptor signaling pathway (GO:0007213), chemical synaptic transmission (GO:0007268), nervous system development (GO:0007399), calcium-mediated signaling (GO:0019722), positive regulation of insulin secretion (GO:0032024), protein modification process (GO:0036211), positive regulation of smooth muscle contraction (GO:0045987), saliva secretion (GO:0046541), acetylcholine receptor signaling pathway (GO:0095500), ligand-gated ion channel signaling pathway (GO:1990806), synaptic transmission, cholinergic (GO:0007271)

GO Molecular Function (6): phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), G protein-coupled acetylcholine receptor activity (GO:0016907), signaling receptor activity (GO:0038023), acetylcholine binding (GO:0042166), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (9): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), basal plasma membrane (GO:0009925), basolateral plasma membrane (GO:0016323), dendrite (GO:0030425), synapse (GO:0045202), postsynaptic membrane (GO:0045211), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Signaling by GPCR	2
Amine ligand-binding receptors	1
Regulation of insulin secretion	1
GPCR downstream signalling	1
Metabolism	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Integration of energy metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
G protein-coupled acetylcholine receptor signaling pathway	3
smooth muscle contraction	2
signal transduction	2
acetylcholine receptor activity	2
plasma membrane region	2
muscle contraction	1
regulation of muscle contraction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
G protein-coupled acetylcholine receptor activity	1
acetylcholine receptor signaling pathway	1
anterograde trans-synaptic signaling	1
system development	1
intracellular signaling cassette	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
protein metabolic process	1
macromolecule modification	1
regulation of smooth muscle contraction	1
positive regulation of muscle contraction	1
body fluid secretion	1
digestive system process	1
secretion by tissue	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
ligand-gated monoatomic ion channel activity	1
chemical synaptic transmission	1
C-type glycerophospholipase activity	1
G protein-coupled amine receptor activity	1
G protein-coupled neurotransmitter receptor activity	1
molecular transducer activity	1

Protein interactions and networks

STRING

1026 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRM3	AGTRAP	Q6RW13	715
CHRM3	BDKRB1	P46663	693
CHRM3	BDKRB2	P30411	604
CHRM3	GABRA1	P14867	603
CHRM3	RGS8	P57771	603
CHRM3	ARRB2	P32121	548
CHRM3	CAMLG	P49069	548
CHRM3	GNAQ	P50148	524
CHRM3	GRM8	O00222	513
CHRM3	GRIK1	P39086	503
CHRM3	CHRNB2	P17787	499
CHRM3	GLRA1	P23415	497
CHRM3	TAC1	P20366	496
CHRM3	RACK1	P25388	491
CHRM3	RIC8B	Q9NVN3	480
CHRM3	GRID1	Q9ULK0	480

IntAct

41 interactions, top by confidence:

A	B	Type	Score
CHRM5	CHRM3	psi-mi:“MI:0915”(physical association)	0.590
CHRM5	CHRM3	psi-mi:“MI:0403”(colocalization)	0.590
CHRM5	CHRM3	psi-mi:“MI:2364”(proximity)	0.590
CHRM3	CHRM5	psi-mi:“MI:2364”(proximity)	0.590
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
RGS4	CHRM3	psi-mi:“MI:0915”(physical association)	0.400
	CHRM3	psi-mi:“MI:0915”(physical association)	0.400
CHRM3	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	CHRM3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CHRM3	psi-mi:“MI:0915”(physical association)	0.400
CHRM3	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
CHRM3	PPP1R9B	psi-mi:“MI:0915”(physical association)	0.400
BSG	CHRM3	psi-mi:“MI:0915”(physical association)	0.370
CD2BP2	CHRM3	psi-mi:“MI:0915”(physical association)	0.370
RAB5IF	CHRM3	psi-mi:“MI:0915”(physical association)	0.370
COMMD7	CHRM3	psi-mi:“MI:0915”(physical association)	0.370
GNAS	CHRM3	psi-mi:“MI:0915”(physical association)	0.370
JAKMIP1	CHRM3	psi-mi:“MI:0915”(physical association)	0.370
MAGED2	CHRM3	psi-mi:“MI:0915”(physical association)	0.370
POM121C	CHRM3	psi-mi:“MI:0915”(physical association)	0.370
SEPTIN3	CHRM3	psi-mi:“MI:0915”(physical association)	0.370
CCDC184	CHRM3	psi-mi:“MI:0915”(physical association)	0.370
SGSM3	CHRM3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (111): ATP1A4 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), CCRN4L (Affinity Capture-MS), PLD2 (Affinity Capture-MS), SLC4A7 (Affinity Capture-MS), FARP2 (Affinity Capture-MS), HEATR3 (Affinity Capture-MS), CAV1 (Affinity Capture-MS), YIPF4 (Affinity Capture-MS), GTPBP2 (Affinity Capture-MS), PTRH2 (Affinity Capture-MS), DCP2 (Affinity Capture-MS), IPO9 (Affinity Capture-MS), GBF1 (Affinity Capture-MS), USP46 (Affinity Capture-MS)

ESM2 similar proteins: A0A2L0VBG2, A1ZAX0, O62169, O77408, P08483, P08911, P08912, P11483, P16395, P17970, P20309, P30974, P30994, P32240, P41595, P41984, P43114, P49578, P56490, Q09388, Q09502, Q18007, Q24352, Q24563, Q28691, Q29J90, Q2KNE5, Q4LBB9, Q4V622, Q5IS53, Q5IS98, Q7JQF1, Q7KVW5, Q868T3, Q8ITC7, Q8ITC9, Q8MJ08, Q920H4, Q9ERZ3, Q9N2A2

Diamond homologs: O02213, O02662, O02667, O13076, O70528, O77621, P04761, P08483, P08908, P08909, P08911, P08912, P0DMS8, P11229, P11483, P11616, P11617, P12657, P15823, P16395, P17124, P18841, P19327, P20309, P22270, P25021, P25099, P25102, P25962, P28190, P28285, P28286, P28335, P28647, P29274, P29275, P29276, P30542, P30543, P34968

SIGNOR signaling

26 interactions.

A	Effect	B	Mechanism
CHRM3	“up-regulates activity”	GNAI1	binding
CHRM3	“up-regulates activity”	GNAI3	binding
CHRM3	“up-regulates activity”	GNAQ	binding
CHRM3	“up-regulates activity”	GNA14	binding
CHRM3	“up-regulates activity”	GNA15	binding
acetylcholine	“up-regulates activity”	CHRM3	“chemical activation”
aclidinium	“down-regulates activity”	CHRM3	“chemical inhibition”
sabcomeline	“up-regulates activity”	CHRM3	“chemical activation”
solifenacin	“down-regulates activity”	CHRM3	“chemical inhibition”
oxybutynin	“down-regulates activity”	CHRM3	“chemical inhibition”
atropine	“down-regulates activity”	CHRM3	“chemical inhibition”
pirenzepine	“down-regulates activity”	CHRM3	“chemical inhibition”
Hexocyclium	“down-regulates activity”	CHRM3	“chemical inhibition”
tiotropium	“down-regulates activity”	CHRM3	“chemical inhibition”
carbachol	“up-regulates activity”	CHRM3	“chemical activation”
bethanechol	“up-regulates activity”	CHRM3	“chemical activation”
(+)-pilocarpine	“up-regulates activity”	CHRM3	“chemical activation”
“1-methyl-3,6-dihydro-2H-pyridine-5-carboxylic acid prop-2-ynyl ester”	“up-regulates activity”	CHRM3	“chemical activation”
arecoline	“up-regulates activity”	CHRM3	“chemical activation”
furtrethonium	“up-regulates activity”	CHRM3	“chemical activation”
trimethyl-[(5-methyl-2-furanyl)methyl]ammonium	“up-regulates activity”	CHRM3	“chemical activation”
Oxotremorine	“up-regulates activity”	CHRM3	“chemical activation”
“oxotremorine M”	“up-regulates activity”	CHRM3	“chemical activation”
dothiepin	“down-regulates activity”	CHRM3	“chemical inhibition”
amitriptyline	“down-regulates activity”	CHRM3	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
protein transport	5	9.1×	5e-03
G protein-coupled receptor signaling pathway	5	7.5×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	110
Likely benign	46
Benign	10

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
29626	NM_001375978.1(CHRM3):c.1173_1184delinsT (p.Pro392fs)	Pathogenic
3063210	GRCh37/hg19 1q43(chr1:237966553-240835685)x1	Pathogenic
60119	GRCh38/hg38 1q43(chr1:238412092-241098768)x1	Pathogenic
974798	NM_001375978.1(CHRM3):c.352G>A (p.Gly118Arg)	Pathogenic
3375478	NM_001375978.1(CHRM3):c.480_499del (p.Val161fs)	Likely pathogenic

SpliceAI

2423 predictions. Top by Δscore:

Variant	Effect	Δscore
1:239678180:TTTTA:T	acceptor_loss	1.0000
1:239678184:A:AG	acceptor_gain	1.0000
1:239678184:A:G	acceptor_loss	1.0000
1:239678185:G:GG	acceptor_gain	1.0000
1:239678185:GGTTT:G	acceptor_gain	1.0000
1:239678284:AACAG:A	donor_loss	1.0000
1:239678287:AGG:A	donor_loss	1.0000
1:239678289:G:GA	donor_loss	1.0000
1:239678290:T:A	donor_loss	1.0000
1:239906542:G:GT	donor_gain	1.0000
1:239663510:G:GT	donor_gain	0.9900
1:239678179:T:G	acceptor_gain	0.9900
1:239678184:AG:A	acceptor_gain	0.9900
1:239678185:GG:G	acceptor_gain	0.9900
1:239678185:GGT:G	acceptor_gain	0.9900
1:239678185:GGTT:G	acceptor_gain	0.9900
1:239907431:A:AG	acceptor_gain	0.9900
1:239907432:G:GG	acceptor_gain	0.9900
1:239678178:A:AG	acceptor_gain	0.9800
1:239704733:A:T	donor_gain	0.9800
1:239767361:G:C	acceptor_gain	0.9800
1:239907429:CCA:C	acceptor_loss	0.9800
1:239907430:CA:C	acceptor_loss	0.9800
1:239907431:AG:A	acceptor_loss	0.9800
1:239907432:GA:G	acceptor_gain	0.9800
1:239907432:GACT:G	acceptor_gain	0.9800
1:239907432:GACTA:G	acceptor_gain	0.9800
1:239671943:A:G	donor_gain	0.9700
1:239678289:G:GG	donor_gain	0.9700
1:239703314:G:GG	donor_gain	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000010892 (1:239586744 C>A), RS1000011803 (1:239771504 T>C), RS1000013746 (1:239676111 A>G), RS1000014114 (1:239643431 C>T), RS1000019159 (1:239459188 T>G), RS1000039492 (1:239603090 A>G), RS1000040748 (1:239690505 A>G), RS1000051140 (1:239464311 C>T), RS1000052985 (1:239522110 T>C), RS1000060824 (1:239766924 C>G), RS1000061616 (1:239587051 C>G,T), RS1000063165 (1:239853809 A>G), RS1000073181 (1:239677248 C>G), RS1000080480 (1:239464046 G>A), RS1000091263 (1:239576073 G>A,C)

Disease associations

OMIM: gene MIM:118494 | disease phenotypes: MIM:100100

GenCC curated gene-disease

Disease	Classification	Inheritance
prune belly syndrome	Strong	Autosomal recessive

Mondo (2): prune belly syndrome (MONDO:0007032), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Prune belly syndrome (Orphanet:2970)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000028	Cryptorchidism
HP:0000069	Abnormality of the ureter
HP:0000072	Hydroureter
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000126	Hydronephrosis
HP:0000130	Abnormality of the uterus
HP:0000144	Decreased fertility
HP:0000217	Xerostomia
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000772	Abnormal rib morphology
HP:0001374	Congenital hip dislocation
HP:0001508	Failure to thrive
HP:0001562	Oligohydramnios
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001636	Tetralogy of Fallot
HP:0001643	Patent ductus arteriosus
HP:0001762	Talipes equinovarus
HP:0002019	Constipation
HP:0002023	Anal atresia
HP:0002205	Recurrent respiratory infections
HP:0002566	Intestinal malrotation
HP:0002580	Volvulus
HP:0002650	Scoliosis

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000041_1	Hypertension	8.000000e-07
GCST001061_4	Platelet count	3.000000e-06
GCST001662_9	Generalized epilepsy	4.000000e-08
GCST001859_37	Thiazide-induced adverse metabolic effects in hypertensive patients	4.000000e-06
GCST002709_22	Electroencephalogram traits	9.000000e-06
GCST003262_300	Post bronchodilator FEV1	7.000000e-07
GCST003262_346	Post bronchodilator FEV1	1.000000e-06
GCST003262_353	Post bronchodilator FEV1	1.000000e-06
GCST003262_354	Post bronchodilator FEV1	1.000000e-06
GCST004185_21	Lung function (FEV1/FVC)	7.000000e-22
GCST004781_5	Sulfasalazine-induced agranulocytosis	3.000000e-08
GCST004814_2	Interleukin-6 (red blood cell fatty acid level interaction)	5.000000e-08
GCST005149_24	Colorectal cancer	6.000000e-06
GCST005150_38	Colorectal cancer	7.000000e-07
GCST006427_29	Depression in smokers	1.000000e-06
GCST006950_47	Feeling worry	4.000000e-08
GCST007430_89	Peak expiratory flow	9.000000e-31
GCST007431_70	Lung function (FEV1/FVC)	2.000000e-31
GCST007432_111	FEV1	1.000000e-17
GCST007679_1	Reflection (response to stress)	7.000000e-06
GCST007692_91	Chronic obstructive pulmonary disease	7.000000e-09
GCST009314_1	Hallucinations in long-term cannabis use	1.000000e-10
GCST009314_2	Hallucinations in long-term cannabis use	6.000000e-11
GCST010816_2	Gut microbiota beta diversity (weighted UniFrac distance)	3.000000e-06
GCST012418_1	Acute respiratory distress syndrome	2.000000e-07
GCST012490_171	Femur bone mineral density x serum urate levels interaction	3.000000e-08

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004530	triglyceride measurement
EFO:0004357	electroencephalogram measurement
EFO:0006873	theta wave measurement
EFO:0004314	forced expiratory volume
EFO:0004713	FEV/FVC ratio
EFO:0004810	interleukin-6 measurement
EFO:0008350	alpha-linoleic acid measurement
EFO:0009589	worry measurement
EFO:0009718	peak expiratory flow
EFO:0009859	reflective stress response
EFO:0007874	gut microbiome measurement
EFO:0004531	urate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
D011535	Prune Belly Syndrome	C16.131.077.745

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2094109 (PROTEIN FAMILY), CHEMBL2095187 (SELECTIVITY GROUP), CHEMBL2111418 (SELECTIVITY GROUP), CHEMBL245 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

207 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 694,762 (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
CHEMBL14	CARBACHOL	4	21,785
CHEMBL1482	BETHANECHOL	4	4,165
CHEMBL42	CLOZAPINE	4	37,581
CHEMBL517712	ATROPINE	4	53,874
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL715	OLANZAPINE	4	40,057
CHEMBL716	QUETIAPINE	4	26,465
CHEMBL85	RISPERIDONE	4	41,869
CHEMBL965	CARBAMOYLCHOLINE	4	22,580
CHEMBL9967	PIRENZEPINE	4	11,458
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1078261	PROPIVERINE	4	4,890
CHEMBL109	VALPROIC ACID	4	65,937
CHEMBL1092	TRIHEXYPHENIDYL HYDROCHLORIDE	4	7,793
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1101	BIPERIDEN	4	11,044
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL1123	DICYCLOMINE	4
CHEMBL1172	DESLORATADINE	4
CHEMBL1179047	CHLOROPROCAINE	4
CHEMBL1184	ACETYLCHOLINE CHLORIDE	4
CHEMBL1186610	ANISOTROPINE	4
CHEMBL1189679	PALONOSETRON	4
CHEMBL1194325	ACLIDINIUM	4
CHEMBL1200356	CYCLACILLIN	4
CHEMBL1200406	DIMENHYDRINATE	4
CHEMBL1200438	TIOCONAZOLE	4

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2165870	CHRM3		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Acetylcholine receptors (muscarinic)

Most potent curated ligand interactions (85 total), top 25:

Ligand	Action	Affinity	Parameter
tiotropium	Antagonist	11.1	pKi
[3H]tiotropium	Antagonist	10.7	pKd
N-methyl scopolamine	Antagonist	10.4	pKi
[3H]QNB	Antagonist	10.4	pKd
[3H]N-methyl scopolamine	Antagonist	10.22	pKd
umeclidinium	Antagonist	10.22	pKi
CHF-6366	Antagonist	10.2	pKd
aclidinium	Antagonist	10.2	pKi
propantheline	Antagonist	10.0	pKi
AE9C90CB	Antagonist	9.9	pKi
atropine	Antagonist	9.8	pKi
ipratropium	Antagonist	9.8	pKi
glycopyrrolate	Antagonist	9.8	pIC50
revefenacin	Antagonist	9.75	pKi
clidinium	Antagonist	9.6	pKi
[3H]darifenacin	Antagonist	9.5	pKd
[3H]4-DAMP	Antagonist	9.4	pKi
scopolamine	Antagonist	9.4	pKi
4-DAMP	Antagonist	9.3	pKi
darifenacin	Antagonist	9.1	pKi
dicyclomine	Antagonist	9.03	pKi
hexocyclium	Antagonist	8.9	pKi
silahexocyclium	Antagonist	8.9	pKi
oxybutynin	Antagonist	8.8	pKi
mepenzolic acid	Antagonist	8.59	pKi

Binding affinities (BindingDB)

641 measured of 712 human assays (744 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL2023760	KD	0.0251 nM
CHEMBL2021997	KD	0.0398 nM
CHEMBL2023613	KD	0.0501 nM
CHEMBL2023749	KD	0.0501 nM
CHEMBL2023612	KD	0.0501 nM
[4-[3-[5-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)ethyl]amino]methyl]-7,8-dihydro-6H-cyclopenta[g]benzotriazol-1-yl]propyl-methylamino]cyclohexyl] 2-hydroxy-2,2-dithiophen-2-ylacetate	IC50	0.062 nM	US-20250230148: CRYSTAL OF FUSED TRICYCLIC DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
CHEMBL2021998	KD	0.0794 nM
[1-[3-[4-[2-[3-[(1R)-1-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)ethyl]amino]ethyl]phenyl]ethylcarbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[4-[2-[[4-[2-[2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)ethylamino]propyl]phenyl]methylamino]-2-oxoethyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[3-[[3-[2-[[2-hydroxy-2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)ethyl]amino]propyl]phenyl]methylcarbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.1 nM	US-9572802: Diamide compounds having muscarinic receptor antagonist and β2 adrenergic receptor agonist activity
[1-[3-[3-[[[2-[3-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)ethyl]amino]methyl]phenyl]acetyl]amino]methyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.1 nM	US-9572802: Diamide compounds having muscarinic receptor antagonist and β2 adrenergic receptor agonist activity
[1-[3-[[4-[4-[(2S)-2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]propyl]anilino]-4-oxobutyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.1 nM	US-8551978: Diamide compounds having muscarinic receptor antagonist and β2 adrenergic receptor agonist activity
[1-[3-[[4-[3-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]anilino]-4-oxobutyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.1 nM	US-8816088: Diamide compounds having muscarinic receptor antagonist and β2 adrenergic receptor agonist activity
[1-[3-[3-[[2-[3-[(1S)-1-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]ethyl]phenyl]acetyl]amino]propyl-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.1 nM	US-8816088: Diamide compounds having muscarinic receptor antagonist and β2 adrenergic receptor agonist activity
NNC 11-1585	KI	0.129 nM
(R)-3-(8-methoxyquinuclidin-8-yl)-1,1-diphenylprop-2-yn-1-ol	KI	0.13 nM
CHEMBL2023750	KD	0.158 nM
CHEMBL2023753	KD	0.158 nM
[(2R)-7,7-dimethyl-7-azoniabicyclo[2.2.1]heptan-2-yl] (2S)-2-cyclopentyl-2-phenylpropanoate	KI	0.16 nM	US-8742134: 7-azoniabicyclo[2.2.1]heptane derivatives, methods of production, and pharmaceutical uses thereof
[(2R)-7,7-dimethyl-7-azoniabicyclo[2.2.1]heptan-2-yl] (2S)-2-cyclopentyl-2-hydroxy-2-phenylacetate	KI	0.18 nM	US-8742134: 7-azoniabicyclo[2.2.1]heptane derivatives, methods of production, and pharmaceutical uses thereof
[(2S)-7,7-dimethyl-7-azoniabicyclo[2.2.1]heptan-2-yl] (2S)-2-cyclopentyl-2-hydroxy-2-phenylacetate	KI	0.18 nM	US-8742134: 7-azoniabicyclo[2.2.1]heptane derivatives, methods of production, and pharmaceutical uses thereof
[1-[3-[3-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)ethyl]amino]methyl]-5-methoxy-2-methylphenyl]carbamoyl]-N-methylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.2 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[5-[[4-[2-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)ethyl]amino]ethyl]-2-methylphenyl]carbamoyl]-N,2-dimethylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.2 nM	US-9572802: Diamide compounds having muscarinic receptor antagonist and β2 adrenergic receptor agonist activity
1-cyclohexyl-3-((R)-3-methoxyquinuclidin-3-yl)-1-phenylprop-2-yn-1-ol	KI	0.2 nM
[(2S)-7,7-dimethyl-7-azoniabicyclo[2.2.1]heptan-2-yl] (2R)-2-cyclopentyl-2-hydroxy-2-phenylacetate	KI	0.22 nM	US-8742134: 7-azoniabicyclo[2.2.1]heptane derivatives, methods of production, and pharmaceutical uses thereof
[1-[3-[5-[[4-[2-[[(2R)-2-(8-hydroxy-2-oxo-4aH-quinolin-5-yl)propyl]amino]propyl]phenyl]carbamoyl]-N,2-dimethylanilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	KI	0.3 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
(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
1-[(2R)-3-[(1R,5S)-3-(cyclopropylmethoxy)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]-6-fluoroindazole	EC50	0.32 nM	US-9670209: Muscarinic agonists
[4-[2-[[2-chloro-4-[[[(2R)-2-hydroxy-2-(5-hydroxy-3-oxo-4H-1,4-benzoxazin-8-yl)ethyl]amino]methyl]-5-methoxyphenyl]carbamoyloxy]ethyl-methylamino]cyclohexyl] 2-hydroxy-2,2-dithiophen-2-ylacetate	IC50	0.38 nM	US-9315463: Cyclohexylamine derivatives having β2 adrenergic agonist and M3 muscarinic antagonist activities
6-fluoro-1-[(2R)-3-[(1R,5S)-3-(2-methoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	0.4 nM	US-9670209: Muscarinic agonists
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 5-[[[3-hydroxy-1-(1-methylpiperidin-4-yl)oxy-1-oxo-2-phenylpropan-2-yl]amino]methyl]thiophene-2-carboxylate	IC50	0.45 nM	US-9636336: Aminoester derivatives
1-(bicyclo[2.2.1]hept-5-en-2-yl)-1-phenyl-3-(piperidin-1-yl)propan-1-ol	KI	0.48 nM
NSC_3746	KI	0.49 nM
1-[(2R)-3-[(1R,5S)-3-(2-methoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]-6-methylindazole	EC50	0.5 nM	US-9670209: Muscarinic agonists
[(1S)-2-(3,5-dichloro-1-oxidopyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl] 5-[[[2-(1-methylpiperidin-4-yl)oxy-2-oxo-1-phenylethyl]amino]methyl]thiophene-2-carboxylate	IC50	0.5 nM	US-9636336: Aminoester derivatives
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
CHEMBL2023752	KD	0.501 nM
4-Diphenylacetoxy-1,1-dimethyl-piperidinium; iodide	KI	0.58 nM
3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N-methylpropan-1-amine	KI	0.6 nM
(S)-(1-methyl-	KI	0.61 nM	US-9828339: Biphenyl derivatives and methods for preparing same
(S)-(1-methyl-	KI	0.63 nM	US-9828339: Biphenyl derivatives and methods for preparing same
CHEMBL2023758	KD	0.631 nM
(S)-(1-methylpyrrolidin-2-yl)-methyl [1,1’-biphenyl]-2-ylcarbamate	KI	0.78 nM	US-9828339: Biphenyl derivatives and methods for preparing same
1-(2-fluoropyridin-3-yl)-3-(3-methoxyquinuclidin-3-yl)-1-phenylprop-2-yn-1-ol	KI	0.79 nM
Ipratropium	KI	0.794 nM
(S)-(1-ethylpyrrolidin-2-yl)methyl [1,1’-biphenyl]-2-ylcarbamate	KI	0.8 nM	US-9828339: Biphenyl derivatives and methods for preparing same
(S)-(1-methyl-	KI	0.8 nM	US-9828339: Biphenyl derivatives and methods for preparing same
[1-[3-[[4-[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2-methylanilino]-4-oxobutyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[4-[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2-methoxyanilino]-4-oxobutyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity
[1-[3-[[4-[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-2,5-dimethylanilino]-4-oxobutyl]-methylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	EC50	1 nM	US-9394275: Diamide compounds having muscarinic receptor antagonist and BETA2 adrenergic receptor agonist activity

ChEMBL bioactivities

3999 potent at pChembl≥5 of 4279 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	TIOTROPIUM BROMIDE
11.00	Kd	0.01	nM	CHEMBL521523
11.00	Ki	0.01	nM	CHEMBL5556228
11.00	Ki	0.01	nM	CHEMBL5527849
11.00	Ki	0.01	nM	CHEMBL1683934
10.92	Kd	0.01202	nM	CHEMBL318812
10.90	Kd	0.01259	nM	CHEMBL539887
10.90	Kd	0.01259	nM	CHEMBL540396
10.90	Ki	0.01259	nM	CHEMBL5527960
10.80	Ki	0.01585	nM	TIOTROPIUM BROMIDE
10.70	Ki	0.01995	nM	TIOTROPIUM BROMIDE
10.70	Kd	0.01995	nM	CHEMBL553448
10.70	Ki	0.01995	nM	CHEMBL5557828
10.70	Kd	0.01995	nM	CHEMBL2103803
10.60	Kd	0.02512	nM	CHEMBL2023760
10.60	Ki	0.02512	nM	TIOTROPIUM BROMIDE
10.60	Kd	0.02512	nM	CHEMBL539887
10.60	Kd	0.02512	nM	CHEMBL489212
10.50	IC50	0.03162	nM	CHEMBL3087959
10.50	Ki	0.03162	nM	TIOTROPIUM
10.50	Kd	0.03162	nM	CHEMBL521696
10.50	Ki	0.03162	nM	CHEMBL521523
10.50	Kd	0.03162	nM	UMECLIDINIUM BROMIDE
10.50	IC50	0.03162	nM	CHEMBL1924027
10.47	Ki	0.034	nM	TIOTROPIUM BROMIDE
10.46	Kd	0.03467	nM	CHEMBL320611
10.40	Kd	0.03981	nM	CHEMBL2021997
10.40	Kd	0.03981	nM	CHEMBL523957
10.40	Kd	0.03981	nM	CHEMBL489211
10.40	Kd	0.03981	nM	CHEMBL490237
10.35	Ki	0.045	nM	QUINUCLIDINYL BENZILATE
10.31	Ki	0.049	nM	CHEMBL1910848
10.30	Kd	0.05012	nM	CHEMBL3084459
10.30	Kd	0.05012	nM	CHEMBL3084457
10.30	Kd	0.05012	nM	CHEMBL3084458
10.30	IC50	0.05012	nM	CHEMBL3087235
10.30	IC50	0.05012	nM	CHEMBL3087230
10.30	Ki	0.05012	nM	CHEMBL3091665
10.30	Ki	0.05012	nM	CHEMBL3426693
10.30	Ki	0.05	nM	CHEMBL370232
10.30	Kd	0.05012	nM	CHEMBL493266
10.30	Kd	0.05012	nM	CHEMBL493265
10.30	IC50	0.05012	nM	TIOTROPIUM BROMIDE
10.30	ED50	0.05	nM	ATROPINE
10.30	IC50	0.05012	nM	CHEMBL1921908
10.30	IC50	0.05012	nM	CHEMBL1924040
10.29	Ki	0.051	nM	QUINUCLIDINYL BENZILATE
10.29	Ki	0.051	nM	TIOTROPIUM BROMIDE
10.27	Ki	0.054	nM	CHEMBL320611
10.22	Ki	0.06	nM	UMECLIDINIUM BROMIDE

PubChem BioAssay actives

2558 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[8-methyl-8-(3-phenylpropyl)-8-azoniabicyclo[3.2.1]octan-3-yl]-2,2-diphenylpropanenitrile bromide	658772: Antagonist potency at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of Ach-induced calcium mobilization by FLIPR analysis relative to control	kd	<0.0001	uM
3-(8-butyl-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl)-2,2-diphenylpropanenitrile bromide	658772: Antagonist potency at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of Ach-induced calcium mobilization by FLIPR analysis relative to control	kd	<0.0001	uM
3-[8-methyl-8-(3-phenoxypropyl)-8-azoniabicyclo[3.2.1]octan-3-yl]-2,2-diphenylpropanenitrile bromide	658772: Antagonist potency at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of Ach-induced calcium mobilization by FLIPR analysis relative to control	kd	<0.0001	uM
Tiotropium Bromide Monohydrate	1056114: Binding affinity to human M3 K523A mutant expressed in HEK293T cells up to 24 hrs by radioligand displacement assay	ki	<0.0001	uM
3-(8-hex-5-enyl-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl)-2,2-diphenylpropanenitrile bromide	658772: Antagonist potency at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of Ach-induced calcium mobilization by FLIPR analysis relative to control	kd	<0.0001	uM
3-(8-hex-5-enyl-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl)-2,2-diphenylpropanenitrile	658772: Antagonist potency at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of Ach-induced calcium mobilization by FLIPR analysis relative to control	kd	<0.0001	uM
3-[8-(cyclopropylmethyl)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl]-2,2-diphenylpropanenitrile bromide	658772: Antagonist potency at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of Ach-induced calcium mobilization by FLIPR analysis relative to control	kd	<0.0001	uM
N-[[4-fluoro-3-[3-[[(3S)-3-methylpiperazin-1-yl]methyl]phenyl]phenyl]methyl]-3-(piperidin-4-ylmethyl)benzamide	390720: Antagonist activity at cloned muscarinic M3 receptor expressed in CHO cells assessed as acetylcholine-induced change in cytosolic calcium concentration by FLIPR assay	kd	<0.0001	uM
diphenyl-[1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-4-yl]methanol bromide	414945: Antagonist activity at human cloned muscarinic M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by single concentration kinetic based-FLIPR assay	kd	<0.0001	uM
N-[[4-fluoro-3-[3-[[(3S)-3-methylpiperazin-1-yl]methyl]phenyl]phenyl]methyl]-3-[(4-methylpiperazin-1-yl)methyl]benzamide	414359: Antagonist activity at human recombinant muscarinic M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by FLIPR based single concentration kinetic assay	kd	<0.0001	uM
[1-[2-[(3-fluorophenyl)methoxy]ethyl]-1-azoniabicyclo[2.2.2]octan-4-yl]-diphenylmethanol bromide	414945: Antagonist activity at human cloned muscarinic M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by single concentration kinetic based-FLIPR assay	kd	<0.0001	uM
[1-[2-[(4-bromophenyl)methoxy]ethyl]-1-azoniabicyclo[2.2.2]octan-4-yl]-diphenylmethanol bromide	414945: Antagonist activity at human cloned muscarinic M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by single concentration kinetic based-FLIPR assay	kd	<0.0001	uM
(1-benzylpiperidin-4-yl)methyl (2S)-2-hydroxy-2-[3-[3-[[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-3-methoxybenzoyl]amino]propoxy]phenyl]-2-phenylacetate	2065076: Displacement of Scopolamine methyl chloride,[N-methyl-3H] from human muscarinic M3 receptor assessed as inhibition constant incubated for 2 hrs by Microbeta scintillation counter	ki	<0.0001	uM
(1-benzylpiperidin-4-yl)methyl (2S)-2-[3-[3-[[2-fluoro-4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-5-methoxybenzoyl]amino]propoxy]phenyl]-2-hydroxy-2-phenylacetate	2065076: Displacement of Scopolamine methyl chloride,[N-methyl-3H] from human muscarinic M3 receptor assessed as inhibition constant incubated for 2 hrs by Microbeta scintillation counter	ki	<0.0001	uM
[(3S)-6-methyl-6-azabicyclo[3.2.1]octan-3-yl] 2,2-diphenylpropanoate	73701: Inhibition of methacholine induced phasic contraction of guinea pig ileum	kd	<0.0001	uM
[(3S)-6-methyl-6-azabicyclo[3.2.1]octan-3-yl] 2-hydroxy-2,2-diphenylacetate	73701: Inhibition of methacholine induced phasic contraction of guinea pig ileum	kd	<0.0001	uM
5-methyl-5-(3-phenoxyazetidin-1-yl)-2,2-diphenylhexanamide	627014: Antagonist activity at human recombinant M3 receptor expressed in CHO-K1 cells assessed as inhibition of carbamoyl choline-induced calcium currents after 4 hrs by fluorimetry	ki	<0.0001	uM
[1-(cyclopropylmethyl)piperidin-4-yl]methyl (2S)-2-[3-[3-[[2-fluoro-4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-5-methoxybenzoyl]amino]propoxy]phenyl]-2-hydroxy-2-phenylacetate;formic acid	2065076: Displacement of Scopolamine methyl chloride,[N-methyl-3H] from human muscarinic M3 receptor assessed as inhibition constant incubated for 2 hrs by Microbeta scintillation counter	ki	<0.0001	uM
(1-ethylpiperidin-4-yl)methyl (2S)-2-[3-[3-[[2-fluoro-4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]-5-methoxybenzoyl]amino]propoxy]phenyl]-2-hydroxy-2-phenylacetate;bis(2,2,2-trifluoroacetic acid)	2065076: Displacement of Scopolamine methyl chloride,[N-methyl-3H] from human muscarinic M3 receptor assessed as inhibition constant incubated for 2 hrs by Microbeta scintillation counter	ki	<0.0001	uM
1-azabicyclo[2.2.2]octan-3-yl 2-hydroxy-2,2-diphenylacetate	141150: Ability of compound to displace (-)-[3H]3-Quinuclidinyl benzilate (-)-[3H]-QNB from Muscarinic acetylcholine receptors in the heart from Guinea Pig.	ki	<0.0001	uM
(1,1-dimethylpiperidin-1-ium-4-yl) 2-cyclopentyl-2-phenylpropanoate	1054736: Displacement of [3H]NMS from recombinant human M3 receptor expressed in CHO-K1 cells after 16 hrs by SPA method	ic50	<0.0001	uM
propan-2-yl 4-[[(2S)-3-(4-hydroxyphenyl)-1-[[2-methyl-7-(naphthalen-2-ylmethyl)imidazo[2,1-b][1,3]thiazol-4-ium-6-yl]methylamino]-1-oxopropan-2-yl]carbamoylamino]benzoate;2,2,2-trifluoroacetate	362480: Antagonist activity at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by single concentration kinetic FLIPR assay	kd	<0.0001	uM
[1-[2-[(4-methylphenyl)methoxy]ethyl]-1-azoniabicyclo[2.2.2]octan-4-yl]-diphenylmethanol bromide	414945: Antagonist activity at human cloned muscarinic M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by single concentration kinetic based-FLIPR assay	kd	<0.0001	uM
[1-[2-[(2-fluorophenyl)methoxy]ethyl]-1-azoniabicyclo[2.2.2]octan-4-yl]-diphenylmethanol bromide	414945: Antagonist activity at human cloned muscarinic M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by single concentration kinetic based-FLIPR assay	kd	<0.0001	uM
cyclohexyl 5-[[(2S)-3-(4-hydroxyphenyl)-1-[[2-methyl-7-(naphthalen-2-ylmethyl)imidazo[2,1-b][1,3]thiazol-4-ium-6-yl]methylamino]-1-oxopropan-2-yl]carbamoylamino]thiophene-2-carboxylate iodide	362480: Antagonist activity at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by single concentration kinetic FLIPR assay	kd	<0.0001	uM
cyclohexyl 5-[[(2S)-3-(4-hydroxyphenyl)-1-[[(3S)-1-[(4-hydroxyphenyl)methyl]-1-methylpiperidin-1-ium-3-yl]amino]-1-oxopropan-2-yl]carbamoylamino]thiophene-2-carboxylate iodide	348849: Antagonist activity at human recombinant muscarinic M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced intracellular Ca2+ mobilization by FLIPR assay	kd	<0.0001	uM
3-[(1R,5S)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octan-3-yl]-2,2-diphenylpropanenitrile bromide	430439: Antagonist activity against human cloned muscarinic M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by measuring ratio of acetylcholine EC50 in presence and absence of compound by FLIPR assay	kd	<0.0001	uM
[(1S,2S,4R,5R)-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonan-7-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate	1204924: Displacement of [3H]NMS from human muscarinic M3 receptor expressing CHO-K1 cells incubated for 60 mins or 6 hrs by liquid scintillation counting	ki	<0.0001	uM
[(3R)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] (2R)-2-piperidin-1-yl-2-thiophen-2-ylpropanoate	631741: Displacement of [3H]NMS from recombinant human M3 receptor expressed in CHO-K1 cells after 16 hrs	ic50	<0.0001	uM
(1,1-dimethylpiperidin-1-ium-4-yl) (2S)-2-cyclopentyl-2-phenylpropanoate bromide	631741: Displacement of [3H]NMS from recombinant human M3 receptor expressed in CHO-K1 cells after 16 hrs	ic50	<0.0001	uM
[(3R)-1-[2-(3-fluorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2S)-2-phenyl-2-piperidin-1-ylpropanoate	631741: Displacement of [3H]NMS from recombinant human M3 receptor expressed in CHO-K1 cells after 16 hrs	ic50	<0.0001	uM
[(3R)-1-[2-(3-chlorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2R)-2-piperidin-1-yl-2-thiophen-2-ylpropanoate	631741: Displacement of [3H]NMS from recombinant human M3 receptor expressed in CHO-K1 cells after 16 hrs	ic50	<0.0001	uM
[(3R)-1-[2-(3-chlorophenyl)ethyl]-1-azoniabicyclo[2.2.2]octan-3-yl] (2S)-2-phenyl-2-piperidin-1-ylpropanoate	631741: Displacement of [3H]NMS from recombinant human M3 receptor expressed in CHO-K1 cells after 16 hrs	ic50	<0.0001	uM
3-[8-methyl-8-(2-phenylmethoxyethyl)-8-azoniabicyclo[3.2.1]octan-3-yl]-2,2-diphenylpropanenitrile iodide	658772: Antagonist potency at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of Ach-induced calcium mobilization by FLIPR analysis relative to control	kd	<0.0001	uM
3-[8-methyl-8-(3-phenylmethoxypropyl)-8-azoniabicyclo[3.2.1]octan-3-yl]-2,2-diphenylpropanenitrile bromide	658772: Antagonist potency at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of Ach-induced calcium mobilization by FLIPR analysis relative to control	kd	<0.0001	uM
3-(8-hexyl-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl)-2,2-diphenylpropanenitrile bromide	658772: Antagonist potency at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of Ach-induced calcium mobilization by FLIPR analysis relative to control	kd	<0.0001	uM
3-[8-methyl-8-(2-phenoxyethyl)-8-azoniabicyclo[3.2.1]octan-3-yl]-2,2-diphenylpropanenitrile bromide	658772: Antagonist potency at human muscarinic acetylcholine M3 receptor expressed in CHO cells assessed as inhibition of Ach-induced calcium mobilization by FLIPR analysis relative to control	kd	<0.0001	uM
[1-[9-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]nonyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	578407: Displacement of [3H]-N-methyl-scopolamine from human muscarinic M3 receptor after 6 hrs by cell based assay	ki	0.0001	uM
3-[(3R)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1,1-dithiophen-2-ylprop-2-yn-1-ol	258308: Binding affinity to human muscarinic M3 receptor	ki	0.0001	uM
[(3R)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] (2S)-2-cyclopentyl-2-hydroxy-2-thiophen-2-ylacetate bromide	430622: Binding affinity to muscarinic M3 receptor	ki	0.0001	uM
3-[(3R)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1,1-diphenylprop-2-yn-1-ol	258308: Binding affinity to human muscarinic M3 receptor	ki	0.0001	uM
3-[(3R)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1,1-di(thiophen-3-yl)prop-2-yn-1-ol	258308: Binding affinity to human muscarinic M3 receptor	ki	0.0001	uM
[1-[9-[[(2R)-2-(3-formamido-4-hydroxyphenyl)-2-hydroxyethyl]amino]nonyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	578407: Displacement of [3H]-N-methyl-scopolamine from human muscarinic M3 receptor after 6 hrs by cell based assay	ki	0.0001	uM
[1-[3-[4-[[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]methyl]anilino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	1204924: Displacement of [3H]NMS from human muscarinic M3 receptor expressing CHO-K1 cells incubated for 60 mins or 6 hrs by liquid scintillation counting	ki	0.0001	uM
[1-[3-[5-[[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1H-quinolin-5-yl)ethyl]amino]pentylamino]-3-oxopropyl]piperidin-4-yl] N-(2-phenylphenyl)carbamate	1204924: Displacement of [3H]NMS from human muscarinic M3 receptor expressing CHO-K1 cells incubated for 60 mins or 6 hrs by liquid scintillation counting	ki	0.0001	uM
(1S,5R)-3-(2,2-dithiophen-2-ylethenyl)-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide	600360: Antagonist activity against human M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by FLIPR	kd	0.0001	uM
N-[[4-fluoro-3-[3-[[(3S)-3-methylpiperazin-1-yl]methyl]phenyl]phenyl]methyl]-3-propanoylbenzamide	390720: Antagonist activity at cloned muscarinic M3 receptor expressed in CHO cells assessed as acetylcholine-induced change in cytosolic calcium concentration by FLIPR assay	kd	0.0001	uM
[1-[2-[(4-fluorophenyl)methoxy]ethyl]-1-azoniabicyclo[2.2.2]octan-4-yl]-diphenylmethanol bromide	414945: Antagonist activity at human cloned muscarinic M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by single concentration kinetic based-FLIPR assay	kd	0.0001	uM
Aclidinium Bromide	1054736: Displacement of [3H]NMS from recombinant human M3 receptor expressed in CHO-K1 cells after 16 hrs by SPA method	ic50	0.0001	uM
N-[[4-fluoro-3-[3-[[(3S)-3-methylpiperazin-1-yl]methyl]phenyl]phenyl]methyl]-3-(morpholin-4-ylmethyl)benzamide	414359: Antagonist activity at human recombinant muscarinic M3 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by FLIPR based single concentration kinetic assay	kd	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetylcholine	affects reaction, increases reaction, affects binding, increases activity	5
Valproic Acid	affects cotreatment, increases expression, affects expression	5
N-Methylscopolamine	affects reaction, increases reaction, affects binding, decreases reaction	5
brucine	affects reaction, increases activity, increases reaction, affects binding	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects expression, increases expression	3
Atropine	affects binding, decreases activity, decreases reaction, increases activity	3
Carbachol	decreases reaction, increases activity, affects binding, increases reaction	3
Aflatoxin B1	affects expression, increases methylation	3
4-diphenylacetoxy-1,1-dimethylpiperidinium	affects binding, decreases reaction	2
N-chloromethylbrucine	affects binding, increases reaction, increases activity	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Nickel	decreases expression	2
Pilocarpine	increases expression, affects binding, increases reaction	2
Scopolamine Derivatives	affects binding, decreases reaction	2
Silicon Dioxide	decreases expression	2
Taurolithocholic Acid	affects activity, affects binding, increases abundance	2
aristolochic acid I	decreases expression	1
securinine	decreases expression	1
methylmercuric chloride	decreases expression	1
oxybutynin	decreases activity, affects binding	1
propionaldehyde	increases expression	1
caracurine	affects binding	1
5-methylfurtrethonium	affects binding, increases reaction	1
acetylmonoethylcholine	increases activity	1
o,p’-DDT	increases expression	1

ChEMBL screening assays

1026 unique, capped per target: 764 binding, 244 functional, 17 admet, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1691873	Binding	Inhibition of human non-selective muscarinic receptor at up to 10 uM	Lersivirine, a nonnucleoside reverse transcriptase inhibitor with activity against drug-resistant human immunodeficiency virus type 1. — Antimicrob Agents Chemother
CHEMBL4144311	ADMET	Antagonist activity at mAChR in human CCRF-CEM cells assessed as inhibition of acetylcholine-stimulated Ca2+ flux pretreated for 25 mins followed by acetylacholine addition measured for 90 secs by calcium dye-based fluorescence assay	Synthesis and SAR of 1,2,3,4-Tetrahydroisoquinoline-Based CXCR4 Antagonists. — ACS Med Chem Lett
CHEMBL4149800	Functional	Antagonist activity at mAChR in human CCRF-CEM cells assessed as inhibition of acetylcholine-induced calcium flux pretreated for 25 mins followed by acetylcholine addition measured for 90 secs by calcium-dye based assay	Discovery of N-Alkyl Piperazine Side Chain Based CXCR4 Antagonists with Improved Drug-like Properties. — ACS Med Chem Lett

Cellosaurus cell lines

11 cell lines: 5 spontaneously immortalized cell line, 4 cancer cell line, 1 transformed cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D1RX	Abcam U-87MG CHRM3 KO	Cancer cell line	Male
CVCL_D9BY	Ubigene HEK293 CHRM3 KO	Transformed cell line	Female
CVCL_E9C5	WIZ03e-H9CAGhM3Dq	Embryonic stem cell	Female
CVCL_F2AZ	CHO-K1 hm3	Spontaneously immortalized cell line	Female
CVCL_H456	CHO-K1/M3	Spontaneously immortalized cell line	Female
CVCL_KB38	GeneBLAzer M3-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_LA03	PathHunter U2OS CHRM3 beta-arrestin	Cancer cell line	Female
CVCL_LA04	PathHunter U2OS CHRM3 Total GPCR Internalization	Cancer cell line	Female
CVCL_RQ18	ValiScreen human CHRM3	Spontaneously immortalized cell line	Female
CVCL_U011	CHO-CHRM3	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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