CHRM2

Summary

CHRM2 (cholinergic receptor muscarinic 2, HGNC:1951) is a protein-coding gene on chromosome 7q33, encoding Muscarinic acetylcholine receptor M2 (P08172). Muscarinic receptor for acetylcholine, a neurotransmitter found in the brain, neuromuscular junctions and the autonomic ganglia.

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 to these receptors 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 2 is involved in mediation of bradycardia and a decrease in cardiac contractility. Multiple alternatively spliced transcript variants have been described for this gene.

Source: NCBI Gene 1129 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 236 total
• Druggable target: yes — 375 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001006630

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1951
Approved symbol	CHRM2
Name	cholinergic receptor muscarinic 2
Location	7q33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000181072
Ensembl biotype	protein_coding
OMIM	118493
Entrez	1129

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000320658, ENST00000401861, ENST00000445907, ENST00000453373, ENST00000471195, ENST00000480591, ENST00000481598, ENST00000680005, ENST00000903439, ENST00000903440, ENST00000903441, ENST00000964717, ENST00000964718, ENST00000964719

RefSeq mRNA: 10 — MANE Select: NM_001006630 NM_000739, NM_001006626, NM_001006627, NM_001006628, NM_001006629, NM_001006630, NM_001006631, NM_001006632, NM_001378972, NM_001378973

CCDS: CCDS5843

Canonical transcript exons

ENST00000680005 — 4 exons

Exon	Start	End
ENSE00001514149	136992187	136992264
ENSE00001602281	136869261	136869418
ENSE00003912278	137014820	137020213
ENSE00003914255	136868652	136868992

Expression profiles

Bgee: expression breadth ubiquitous, 107 present calls, max score 90.06.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2955 / max 200.0735, expressed in 327 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81377	3.0568	289
81381	0.3887	117
81382	0.2909	116
81378	0.2395	119
81379	0.1897	95
81383	0.0509	34
81380	0.0506	27
81376	0.0285	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	90.06	gold quality
right atrium auricular region	UBERON:0006631	87.31	gold quality
apex of heart	UBERON:0002098	87.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.58	gold quality
cardiac atrium	UBERON:0002081	85.53	gold quality
heart left ventricle	UBERON:0002084	84.06	gold quality
gall bladder	UBERON:0002110	83.20	gold quality
cardiac ventricle	UBERON:0002082	82.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.40	silver quality
heart	UBERON:0000948	78.21	gold quality
colonic epithelium	UBERON:0000397	77.46	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	75.04	gold quality
right lung	UBERON:0002167	73.10	gold quality
left ventricle myocardium	UBERON:0006566	72.88	gold quality
cardiac muscle of right atrium	UBERON:0003379	72.41	gold quality
smooth muscle tissue	UBERON:0001135	70.51	gold quality
mucosa of stomach	UBERON:0001199	68.81	gold quality
colon	UBERON:0001155	68.64	gold quality
lower esophagus muscularis layer	UBERON:0035833	67.92	gold quality
lower esophagus	UBERON:0013473	67.81	gold quality
large intestine	UBERON:0000059	67.67	gold quality
diaphragm	UBERON:0001103	67.43	gold quality
cortical plate	UBERON:0005343	66.20	gold quality
urinary bladder	UBERON:0001255	66.18	gold quality
vermiform appendix	UBERON:0001154	65.96	gold quality
prefrontal cortex	UBERON:0000451	65.81	gold quality
rectum	UBERON:0001052	65.77	gold quality
pancreatic ductal cell	CL:0002079	65.06	silver quality
fundus of stomach	UBERON:0001160	64.82	gold quality
intestine	UBERON:0000160	63.89	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.70
E-MTAB-11268	no	1272.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting CHRM2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587

Literature-anchored findings (GeneRIF, showing 40)

• Muscarinic M2 receptor density is increased in the frontal and temporal cortex of patients with Alzheimer’s disease with psychotic symptoms compared with those without these symptoms. (PMID:11552008)
• trafficking of M2 muscarinic acetylcholine receptor to clathrin-derived early endosomes following clathrin-independent endocytosis (PMID:12093817)
• Results are consistent with a gender-specific role of the CHRM2 gene in depression in women. (PMID:12116189)
• There is a higher concentration of muscarinic-2 receptors in the brain of aging subjects with an apolipoprotein E-epsilon4 allele. (PMID:12774299)
• role of M1 and M2 muscarinic receptors expressed by human L cells in the control of GLP-1 secretion. (PMID:12810581)
• molecular model of orthosteric and allosteric binding sites (PMID:12825791)
• Data characterize the 5’ untranslated region of the CHRM2 gene as expressed in human airway smooth muscle (HASM) cells. (PMID:14512373)
• Whereas normal detrusor contractions are mediated by the M(3) receptor subtype, in patients with neurogenic bladder dysfunction as well as certain organ transplant donors, contractions can be mediated by the M(2) muscarinic receptor subtype. (PMID:14751843)
• Linkage and linkage disequilibrium between frontal theta band, visual evoked brain potentials and single nucleotide polymorphism(SNP) from CHRM2 on chromosome 7. Linkage disequilibrium between CHRM2 SNPs and parietal delta band visual evoked potentials. (PMID:15210286)
• Extracts of M2 muscarinic receptor from Sf9 cells therefore contain aggregates that are at least trimeric, and the levels detected point to the existence of larger complexes. The data also suggest that the oligomers coexist with a population of monomers (PMID:15255931)
• variations in the CHRM2 gene is associated with alcohol dependence, drug dependence and affective disorders (PMID:16000316)
• M2 acetylcholine receptor down-regulation in brains with Alzheimer’s disease(AD) affects expression of several genes and proteins with major functions in the pathology of AD, including beta-secretase BACE1 and several modulators of tau protein. (PMID:16181410)
• Increased phosphorylation of M1 and M2 mAChRs underlies sequestration of these receptors after transient hypoxia. Distinct pathways involving CK1alpha and GRK2 mediated sequestration of M1 and M2 mAChRs after transient hypoxic-induced oxidative stress. (PMID:16336219)
• 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)
• These data suggest that DNA sequence variation at the CHRM2 locus is a potential modifier of HR recovery in the sedentary state and after short-term endurance training in healthy individuals. (PMID:16501017)
• Reduced muscarinic type 2 receptor binding in subjects with bipolar disorder relative to both healthy controls and subjects with major depressive disorder. (PMID:16818863)
• Genetic linkage and association findings which implicate the gene encoding the muscarinic acetylcholine receptor M2 (CHRM2) in the modulation of a scalp-recorded electrophysiological phenotype. (PMID:16823639)
• Full-length RGS3, RGS3T, and the core domain of RGS3 were equally effective in antagonizing inhibition of Ca(V)2.3 through M(2)R. (PMID:16855219)
• Using a test of within-family association, a highly significant association was found between the CHRM2 gene and intelligence. The strongest association was between rs324650 and performance IQ. (PMID:17081262)
• possible role of the urothelium in controlling M2 mediated contractile phenotype for human bladders (PMID:17123299)
• Associated with multiple single nucleotide polymorphisms across CHRM2 and Performance IQ, as measured by the Wechsler Adult Intelligence Scale. (PMID:17160701)
• 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)
• CHRM2 variation may contribute to the genetic component of variation in personality traits (PMID:17468496)
• Monomers of the M2 receptor therefore can be assembled into tetramers with binding properties that closely resemble those of the muscarinic receptor in myocardial preparations. (PMID:17552496)
• Poly I:C caused decreased M2R in airway smooth muscle cells by interacting with TLR3. (PMID:17851256)
• a key epitope of the M2 muscarinic acetylcholine receptor is M(2)Trp(422) in position 7.35 that is located at the extracellular top of transmembrane helix 7 and that contacts, in the inactive receptor, the extracellular loop E2 (PMID:17890226)
• Using a denser coverage of SNPs in the CHRM2 gene, we confirmed the 5’UTR regions to be most interesting in the context of intelligence, and ruled out other regions of this gene (PMID:17996044)
• Results suggest that autocrine/paracrine effects occur concerning tenocytes in tendinosis, with up- and downregulation in levels of M(2)R immunoreactivity in tenocytes and blood vessel cells during the various stages of tendinosis. (PMID:17999088)
• In progressive supranuclear palsy: there were no changes in M2 muscarinic receptor densitY (PMID:18282687)
• Association analyses of a candidate gene, CHRM2, previously of interest in the Collaborative Study on the Genetics of Alcoholism, suggest that it is involved in a general externalizing phenotype (PMID:18316677)
• 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)
• We have identified a novel missense mutation (C722G) in the CHRM2 gene associated with familial dilated cardiomyopathy, which correlates with autoantibodies against CHRM2. Patients with C722G mutation have more progressive disease (PMID:18451336)
• 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)
• DNA sequence variation at the CHRM2 locus is a determinant of cardiac autonomic function in the postexercise early recovery phase and predicts cardiac mortality after AMI (PMID:18979273)
• Data fail to support association with the CHRM2 polymorphisms previously implicated in the genetic aetiology of depression. (PMID:19181679)
• No association of A/T polymorphism was found with asthma (p=0.865 for genotypes and p=0.782 for alleles). (PMID:19308904)
• Distinct changes of M(2) receptor signaling through both preferential and non-preferential G-proteins consequent to membrane cholesterol depletion that occur at the level of receptor/G-protein/effector protein interactions in the cell membrane. (PMID:19374848)
• CHRM2 does not appear to play a role in cognitive ability (PMID:19418213)
• a variant in the muscarinic acetylcholine receptor 2 gene (CHRM2) may have a role in nicotine addiction (PMID:19644963)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrm2a	ENSDARG00000098612
danio_rerio	chrm2b	ENSDARG00000116374
mus_musculus	Chrm2	ENSMUSG00000045613
rattus_norvegicus	Chrm2	ENSRNOG00000046972

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), 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), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

Muscarinic acetylcholine receptor M2 — P08172 (reviewed: P08172)

All UniProt accessions (2): A4D1Q0, P08172

UniProt curated annotations — full annotation on UniProt →

Function. Muscarinic receptor for acetylcholine, a neurotransmitter found in the brain, neuromuscular junctions and the autonomic ganglia. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. CHRM2 is coupled to G(i)/G(o) (GNAI1 or GNAO1) G proteins and mediates signaling by inhibiting adenylate cyclase activity.

Subunit / interactions. Interacts (when phosphorylated) with ARRB1 and ARRB2; the interaction is associated with internalization of the receptor and short-term desensitization to the ligand. Interacts with RACK1; the interaction regulates CHRM2 internalization.

Subcellular location. Cell membrane. Postsynaptic cell membrane.

Post-translational modifications. Phosphorylation of the P-X-P-P motif promotes association with beta-arrestin (ARRB1 and/or ARRB2), leading to receptor desensitization and negative regulation of G-protein coupled receptor signaling.

Disease relevance. Major depressive disorder (MDD) [MIM:608516] A common psychiatric disorder. It is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Activity regulation. Activated by allosteric modulator LY2119620.

Domain organisation. The P-X-P-P motif is phosphorylated in response to ligand binding, promoting. association with beta-arrestin (ARRB1 and/or ARRB2).

Induction. Up-regulated in response to enterovirus 71 (EV71) infection.

Polymorphism. Genetic variations in CHRM2 can influence susceptibility to alcoholism [MIM:103780].

Similarity. Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM2 sub-subfamily.

RefSeq proteins (10): NP_000730, NP_001006627, NP_001006628, NP_001006629, NP_001006630, NP_001006631, NP_001006632, NP_001006633, NP_001365901, NP_001365902 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000995	Musac_Ach_rcpt	Family
IPR001065	Musac_Ach_M2_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (62 total): helix 15, modified residue 10, topological domain 8, transmembrane region 7, mutagenesis site 7, compositionally biased region 4, glycosylation site 4, disulfide bond 2, chain 1, region of interest 1, short sequence motif 1, turn 1, strand 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
5ZKC	X-RAY DIFFRACTION	2.3
5YC8	X-RAY DIFFRACTION	2.5
5ZK3	X-RAY DIFFRACTION	2.6
8J8R	ELECTRON MICROSCOPY	2.9
5ZKB	X-RAY DIFFRACTION	2.95
3UON	X-RAY DIFFRACTION	3
5ZK8	X-RAY DIFFRACTION	3
8JAF	ELECTRON MICROSCOPY	3.1
7T94	ELECTRON MICROSCOPY	3.16
8J97	ELECTRON MICROSCOPY	3.2
7T8X	ELECTRON MICROSCOPY	3.21
7T96	ELECTRON MICROSCOPY	3.22
7T90	ELECTRON MICROSCOPY	3.32
4MQS	X-RAY DIFFRACTION	3.5
6OIK	ELECTRON MICROSCOPY	3.6
4MQT	X-RAY DIFFRACTION	3.7
6U1N	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08172-F1	72.87	0.52

Antibody-complex structures (SAbDab): 11 — 4MQS, 4MQT, 6OIK, 6U1N, 7T8X, 7T90, 7T94, 7T96, 8J8R, 8J97, 8JAF

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 (10): 232, 302, 307, 309, 310, 311, 315, 446, 450, 465

Disulfide bonds (2): 96–176, 413–416

Glycosylation sites (4): 2, 3, 6, 9

Mutagenesis-validated functional residues (7):

Position	Phenotype
58	nearly abolishes signaling via downstream effectors.
103	reduced affinity for acetylcholine. abolishes signaling via downstream effectors.
206	abolishes signaling via downstream effectors.
307–310	impaired interaction with arrb1 and arrb2.
308	impaired interaction with arrb1 and arrb2.
340–343	does not affect interaction with arrb1 and arrb2.
404	reduced affinity for acetylcholine. reduces signaling via downstream effectors.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-390648	Muscarinic acetylcholine receptors
R-HSA-418594	G alpha (i) signalling events
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-162582	Signal Transduction
R-HSA-199991	Membrane Trafficking
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-500792	GPCR ligand binding
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 136 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_MUSCLE_CONTRACTION, GOCC_COATED_VESICLE, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SMOOTH_MUSCLE_CONTRACTION, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_SYNAPTIC_SIGNALING

GO Biological Process (14): regulation of smooth muscle contraction (GO:0006940), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), 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), regulation of heart contraction (GO:0008016), response to virus (GO:0009615), presynaptic modulation of chemical synaptic transmission (GO:0099171), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled acetylcholine receptor activity (GO:0016907), arrestin family protein binding (GO:1990763), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (13): nucleolus (GO:0005730), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), dendrite (GO:0030425), clathrin-coated endocytic vesicle membrane (GO:0030669), ciliary basal body (GO:0036064), synapse (GO:0045202), postsynaptic membrane (GO:0045211), presynapse (GO:0098793), cholinergic synapse (GO:0098981), cell junction (GO:0030054)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Signaling by GPCR	2
Amine ligand-binding receptors	1
GPCR downstream signalling	1
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Vesicle-mediated transport	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	4
G protein-coupled acetylcholine receptor signaling pathway	3
cellular anatomical structure	3
synapse	2
regulation of muscle contraction	1
smooth muscle contraction	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor 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
heart contraction	1
regulation of blood circulation	1
response to other organism	1
modulation of chemical synaptic transmission	1
presynapse	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled amine receptor activity	1
acetylcholine receptor activity	1
G protein-coupled neurotransmitter receptor activity	1
protein binding	1
transmembrane signaling receptor activity	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
intraciliary transport particle	1

Protein interactions and networks

STRING

1352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRM2	GABRA2	P47869	808
CHRM2	TAS2R16	Q9NYV7	719
CHRM2	CHRNB2	P17787	710
CHRM2	ANKK1	Q8NFD2	702
CHRM2	COMT	P21964	686
CHRM2	CHRNA2	Q15822	684
CHRM2	SLC6A4	P31645	683
CHRM2	GRM8	O00222	667
CHRM2	RGS9	O75916	648
CHRM2	PLEKHG2	Q9H7P9	648
CHRM2	ADH7	P40394	645
CHRM2	CHRNA5	P30532	628
CHRM2	ADH1B	P00325	614
CHRM2	GABRA1	P14867	603
CHRM2	CACNA1B	Q00975	587

IntAct

31 interactions, top by confidence:

A	B	Type	Score
CHRM2	GPRASP1	psi-mi:“MI:0407”(direct interaction)	0.440
CHRM2	GPRASP2	psi-mi:“MI:0407”(direct interaction)	0.440
CHRM2	SH3GL1	psi-mi:“MI:0915”(physical association)	0.400
SH3GL2	CHRM2	psi-mi:“MI:0915”(physical association)	0.400
CHRM2	ANXA2	psi-mi:“MI:0915”(physical association)	0.400
	CHRM2	psi-mi:“MI:0915”(physical association)	0.400
CHRM2	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	CHRM2	psi-mi:“MI:0915”(physical association)	0.400
CHRM2	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CHRM2	psi-mi:“MI:0915”(physical association)	0.400
CHRM2	TMEM8B	psi-mi:“MI:0915”(physical association)	0.370
SLC52A2	CHRM2	psi-mi:“MI:0915”(physical association)	0.370
GJC2	CHRM2	psi-mi:“MI:0915”(physical association)	0.370
HERPUD1	CHRM2	psi-mi:“MI:0915”(physical association)	0.370
MDH1	CHRM2	psi-mi:“MI:0915”(physical association)	0.370
TSPAN33	CHRM2	psi-mi:“MI:0915”(physical association)	0.370
TSPAN7	CHRM2	psi-mi:“MI:0915”(physical association)	0.370
SHISA4	CHRM2	psi-mi:“MI:0915”(physical association)	0.370
CHRM2	CHRM2	psi-mi:“MI:0915”(physical association)	0.370
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	SNAP23	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
CHRM2	Arrb2	psi-mi:“MI:0403”(colocalization)	0.270
CHRM2	Lamp1	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (21): RGS7 (Reconstituted Complex), CHRM2 (Proximity Label-MS), CHRM2 (Two-hybrid), TMEM8B (Two-hybrid), SLC52A2 (Two-hybrid), GJC2 (Two-hybrid), HERPUD1 (Two-hybrid), MDH1 (Two-hybrid), TSPAN33 (Two-hybrid), TSPAN7 (Two-hybrid), SHISA4 (Two-hybrid), CHRM2 (Proximity Label-MS), CHRM2 (Affinity Capture-MS), CHRM2 (Affinity Capture-MS), CHRM2 (Affinity Capture-MS)

ESM2 similar proteins: O02777, O08530, P06199, P08172, P08173, P08483, P08485, P08911, P08912, P0C0L6, P10980, P17200, P20272, P21453, P21554, P28335, P30372, P30544, P32211, P34969, P41985, P47746, P48303, P56490, P56971, Q333S9, Q56H79, Q5E9P3, Q5IS53, Q5IS66, Q5IS73, Q5IS98, Q60F97, Q6W5P4, Q71SP5, Q801M1, Q868T3, Q8BZP8, Q90352, Q91559

Diamond homologs: A1ZAX0, A5A4K9, A5A4L1, F1MV99, O02664, O08725, O08858, O19014, O43193, O55040, O77723, O88319, O88634, O88855, O97772, P06199, P08172, P08173, P08485, P10980, P17200, P19020, P20288, P20789, P20905, P21917, P28646, P30372, P30729, P30872, P30873, P30937, P30938, P30989, P31391, P32211, P32300, P32745, P33533, P33534

SIGNOR signaling

26 interactions.

A	Effect	B	Mechanism
CHRM2	up-regulates	GNAO1
CHRM2	“up-regulates activity”	GNAI1	binding
CHRM2	“up-regulates activity”	GNAI3	binding
CHRM2	“up-regulates activity”	GNAO1	binding
acetylcholine	“up-regulates activity”	CHRM2	“chemical activation”
aclidinium	“down-regulates activity”	CHRM2	“chemical inhibition”
sabcomeline	“up-regulates activity”	CHRM2	“chemical activation”
solifenacin	“down-regulates activity”	CHRM2	“chemical inhibition”
oxybutynin	“down-regulates activity”	CHRM2	“chemical inhibition”
dicyclomine	“down-regulates activity”	CHRM2	“chemical inhibition”
Hexocyclium	“down-regulates activity”	CHRM2	“chemical inhibition”
atropine	“down-regulates activity”	CHRM2	“chemical inhibition”
pirenzepine	“down-regulates activity”	CHRM2	“chemical inhibition”
tiotropium	“down-regulates activity”	CHRM2	“chemical inhibition”
carbachol	“up-regulates activity”	CHRM2	“chemical activation”
bethanechol	“up-regulates activity”	CHRM2	“chemical activation”
(+)-pilocarpine	“up-regulates activity”	CHRM2	“chemical activation”
“1-methyl-3,6-dihydro-2H-pyridine-5-carboxylic acid prop-2-ynyl ester”	“up-regulates activity”	CHRM2	“chemical activation”
arecoline	“up-regulates activity”	CHRM2	“chemical activation”
furtrethonium	“up-regulates activity”	CHRM2	“chemical activation”
trimethyl-[(5-methyl-2-furanyl)methyl]ammonium	“up-regulates activity”	CHRM2	“chemical activation”
Oxotremorine	“up-regulates activity”	CHRM2	“chemical activation”
“oxotremorine M”	“up-regulates activity”	CHRM2	“chemical activation”
dothiepin	“down-regulates activity”	CHRM2	“chemical inhibition”
amitriptyline	“down-regulates activity”	CHRM2	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	125
Likely benign	81
Benign	26

Top pathogenic / likely-pathogenic (0)

SpliceAI

1544 predictions. Top by Δscore:

Variant	Effect	Δscore
7:136869258:A:AG	acceptor_gain	1.0000
7:136869259:A:G	acceptor_gain	1.0000
7:136869414:GACAG:G	donor_gain	1.0000
7:136869417:AGGT:A	donor_loss	1.0000
7:136869418:GGTA:G	donor_loss	1.0000
7:136869419:G:C	donor_loss	1.0000
7:136869419:G:GG	donor_gain	1.0000
7:136869420:T:A	donor_loss	1.0000
7:136992265:G:GG	donor_gain	1.0000
7:136869255:T:A	acceptor_gain	0.9900
7:136869259:AGATC:A	acceptor_loss	0.9900
7:136869260:G:GG	acceptor_gain	0.9900
7:136869260:GATCA:G	acceptor_gain	0.9900
7:136923281:ACTGT:A	acceptor_gain	0.9900
7:137014816:GCAG:G	acceptor_loss	0.9900
7:137014817:CAGG:C	acceptor_loss	0.9900
7:137014818:A:AG	acceptor_gain	0.9900
7:137014818:A:C	acceptor_loss	0.9900
7:137014819:G:GC	acceptor_loss	0.9900
7:137014819:G:GG	acceptor_gain	0.9900
7:136869260:GA:G	acceptor_gain	0.9800
7:136869260:GATC:G	acceptor_gain	0.9800
7:136869264:A:AG	acceptor_gain	0.9800
7:136923285:T:TA	acceptor_gain	0.9800
7:136939105:T:A	acceptor_gain	0.9800
7:136968261:A:G	donor_gain	0.9800
7:137014818:AG:A	acceptor_gain	0.9800
7:137014819:GG:G	acceptor_gain	0.9800
7:137014819:GGT:G	acceptor_gain	0.9800
7:137014819:GGTTT:G	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000036552 (7:136941081 C>A,T), RS1000062900 (7:136986819 T>C), RS1000073166 (7:136889301 T>C), RS1000097880 (7:136959781 C>A), RS1000124834 (7:136899339 T>G), RS1000136781 (7:136941400 C>G,T), RS1000160381 (7:136978138 G>A), RS1000177944 (7:136977707 A>G), RS1000231400 (7:136978445 T>A), RS1000232436 (7:136890030 C>T), RS1000234552 (7:136935014 G>T), RS1000256560 (7:137008966 A>T), RS1000261290 (7:136910940 G>A,T), RS1000274673 (7:136871362 G>A), RS1000284085 (7:136934096 G>C)

Disease associations

OMIM: gene MIM:118493 | disease phenotypes: MIM:115200

GenCC curated gene-disease

Mondo (2): cardiomyopathy (MONDO:0004994), dilated cardiomyopathy 1A (MONDO:0007269)

Orphanet (2): Rare cardiomyopathy (Orphanet:167848), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751)

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001969_16	Heart rate	1.000000e-12
GCST002938_42	Copper levels	9.000000e-06
GCST003818_80	Resting heart rate	3.000000e-18
GCST005788_15	Heart rate response to recovery post exercise	2.000000e-10
GCST005789_15	Resting heart rate	6.000000e-09
GCST005846_9	Heart rate response to recovery post exercise (10 sec)	7.000000e-11
GCST005847_11	Heart rate response to recovery post exercise (20 sec)	6.000000e-12
GCST005848_17	Heart rate response to recovery post exercise (50 sec)	1.000000e-14
GCST005849_2	Heart rate response to recovery post exercise (40 sec)	4.000000e-13
GCST005850_8	Heart rate response to recovery post exercise (30 sec)	5.000000e-13
GCST006626_17	Pulse pressure	2.000000e-09
GCST007325_83	General risk tolerance (MTAG)	8.000000e-10
GCST010320_64	PR interval	1.000000e-07
GCST010321_34	PR interval	5.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009185	heart rate response to recovery post exercise
EFO:0005763	pulse pressure measurement
EFO:0008579	risk-taking behaviour
EFO:0004462	PR interval

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2094109 (PROTEIN FAMILY), CHEMBL2095187 (SELECTIVITY GROUP), CHEMBL2095219 (SELECTIVITY GROUP), CHEMBL211 (SINGLE PROTEIN), CHEMBL2111352 (SELECTIVITY GROUP), CHEMBL2111445 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

375 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 673,071 (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
CHEMBL1004	DOXYLAMINE	4	12,263
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1078261	PROPIVERINE	4	4,890
CHEMBL1088	MESORIDAZINE	4	12,814
CHEMBL1092	TRIHEXYPHENIDYL HYDROCHLORIDE	4	7,793
CHEMBL1094636	NIRAPARIB	4	6,433
CHEMBL11	IMIPRAMINE	4
CHEMBL1101	BIPERIDEN	4
CHEMBL110691	CHLORMADINONE ACETATE	4
CHEMBL111	RIMONABANT	4
CHEMBL1112	ARIPIPRAZOLE	4
CHEMBL1113	AMOXAPINE	4
CHEMBL1123	DICYCLOMINE	4
CHEMBL1171837	PONATINIB	4
CHEMBL1172	DESLORATADINE	4
CHEMBL1173655	AFATINIB	4

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs324650	Other	3	nicotine	Tobacco Use Disorder

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs324650	CHRM2	3	2.50	1	nicotine
rs1824024	CHRM2		0.00	0
rs2061174	CHRM2		0.00	0
rs6962027	CHRM2		0.00	0
rs8191992	CHRM2		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 (105 total), top 25:

Ligand	Action	Affinity	Parameter
tiotropium	Antagonist	10.7	pKi
[3H]QNB	Antagonist	10.6	pKd
Cy3B-telenzepine	Antagonist	10.4	pKi
[3H]tiotropium	Antagonist	10.3	pKd
[3H]iperoxo	Agonist	10.1	pKd
aclidinium	Antagonist	10.1	pIC50
NNC 11-1585	Full agonist	10.1	pKi
[3H]N-methyl scopolamine	Antagonist	9.9	pKd
umeclidinium	Antagonist	9.82	pKi
ipratropium	Antagonist	9.8	pKi
iperoxo	Full agonist	9.8	pEC50
tripitramine	Antagonist	9.6	pKi
[3H]clidinium	Antagonist	9.6	pKd
revefenacin	Antagonist	9.52	pKi
THRX160209	Antagonist	9.5	pKi
propantheline	Antagonist	9.5	pKi
glycopyrrolate	Antagonist	9.5	pIC50
[3H]4NMPB	Antagonist	9.4	pKd
atropine	Antagonist	9.2	pKi
mepenzolic acid	Antagonist	9.17	pKi
[3H]AF DX-384	Antagonist	9.0	pKd
dexetimide	Antagonist	8.9	pKi
[3H]acetylcholine	Agonist	8.8	pKd
Alexa-488-telenzepine	Antagonist	8.8	pKi
scopolamine	Antagonist	8.7	pKi

Binding affinities (BindingDB)

430 measured of 473 human assays (512 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[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
NSC_104911	KI	0.1 nM
NNC 11-1585	KI	0.129 nM
(R)-3-(3-methoxyquinuclidin-3-yl)-1,1-di(thiophen-2-yl)prop-2-yn-1-ol	KI	0.2 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
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
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
(R)-3-(3-methoxyquinuclidin-3-yl)-1,1-di(thiophen-3-yl)prop-2-yn-1-ol	KI	0.4 nM
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
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 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
1-[(2R)-3-[(1R,5S)-3-(2-ethoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	0.79 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-(2-ethoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]-6-methylindazole	EC50	0.79 nM	US-9670209: Muscarinic agonists
(R)-3-((R)-3-methoxyquinuclidin-3-yl)-1-phenyl-1-(pyridin-3-yl)prop-2-yn-1-ol	KI	0.79 nM
tert-butyl (5S)-3-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylate	EC50	1 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-(cyclopropylmethoxy)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	1.3 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-(cyclopropylmethoxy)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]-6-methylindazole	EC50	1.3 nM	US-9670209: Muscarinic agonists
6-fluoro-1-[(2R)-2-methyl-3-[(1R,5S)-3-prop-2-enoxy-8-azabicyclo[3.2.1]octan-8-yl]propyl]indazole	EC50	1.3 nM	US-9670209: Muscarinic agonists
3-(3-methoxyquinuclidin-3-yl)-1-phenyl-1-(pyridin-3-yl)prop-2-yn-1-ol	KI	1.3 nM
CAS_62865	KI	1.5 nM
NSC_132947	KI	1.58 nM
CHEMBL195011	EC50	1.74 nM
5-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-6-chloro-1,3-dihydro-indol-2-one	KI	1.9 nM
NNC 11-1607	KI	2.4 nM
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)	KI	2.92 nM
8-[4-(4-fluorophenyl)-4-keto-butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	KI	2.94 nM	US-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
1-cyclopentyl-3-(3-methoxyquinuclidin-3-yl)-1-phenylprop-2-yn-1-ol	KI	3.2 nM
ATR	IC50	3.2 nM	US-9333195: Quinuclidine derivatives and medicinal compositions containing the same
1-[(2R)-3-[(1R,5S)-3-(2-methoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	4 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-cyclopentyloxy-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	4 nM	US-9670209: Muscarinic agonists
1-(6-fluoropyridin-3-yl)-3-(3-methoxyquinuclidin-3-yl)-1-phenylprop-2-yn-1-ol	KI	4 nM
1-Cyclohexyl-1-phenyl-3-pyrrolidin-1-yl-propan-1-ol	KI	4.6 nM
CHEMBL196218	EC50	4.79 nM
(R)-1,1-bis(3-fluorophenyl)-3-(3-methoxyquinuclidin-3-yl)prop-2-yn-1-ol	KI	5 nM
Enablex	KI	5.5 nM
6-methoxy-1-[(2R)-3-[(1R,5S)-3-(2-methoxyethyl)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	6.3 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-(2-methoxyethylidene)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	6.3 nM	US-9670209: Muscarinic agonists
CHEMBL194008	EC50	6.46 nM
Quinidine	KI	7.5 nM
1-[(2R)-2-methyl-3-[(1R,5S)-3-prop-2-enoxy-8-azabicyclo[3.2.1]octan-8-yl]propyl]indazole	EC50	7.9 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-(cyclobutylmethoxy)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]indazole	EC50	7.9 nM	US-9670209: Muscarinic agonists
1-[(2R)-2-methyl-3-[(1R,5S)-3-propoxy-8-azabicyclo[3.2.1]octan-8-yl]propyl]indazole	EC50	7.9 nM	US-9670209: Muscarinic agonists
1-[(2R)-3-[(1R,5S)-3-(cyclopropylmethoxy)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]-6-methoxyindazole	EC50	10 nM	US-9670209: Muscarinic agonists
1-[(2R)-2-methyl-3-[(1R,5S)-3-prop-2-ynoxy-8-azabicyclo[3.2.1]octan-8-yl]propyl]indazole	EC50	10 nM	US-9670209: Muscarinic agonists
6-methoxy-1-[(2R)-2-methyl-3-[(1R,5S)-3-prop-2-ynoxy-8-azabicyclo[3.2.1]octan-8-yl]propyl]indazole	EC50	10 nM	US-9670209: Muscarinic agonists
CAS_312-45-8	KI	11 nM
1-[(2R)-3-[(1R,5S)-3-(cyclopropylmethoxy)-8-azabicyclo[3.2.1]octan-8-yl]-2-methylpropyl]-3-methylindazole	EC50	13 nM	US-9670209: Muscarinic agonists

ChEMBL bioactivities

3996 potent at pChembl≥5 of 4354 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL76164
10.92	Kd	0.01202	nM	CHEMBL318812
10.90	Kd	0.01259	nM	CHEMBL539887
10.70	Ki	0.01995	nM	TIOTROPIUM BROMIDE
10.70	Ki	0.02	nM	CHEMBL6161708
10.67	Ki	0.0215	nM	TIOTROPIUM BROMIDE
10.52	Ki	0.03	nM	CHEMBL2114068
10.52	Ki	0.03	nM	CHEMBL349497
10.52	Ki	0.03	nM	CHEMBL164705
10.52	Ki	0.03	nM	CHEMBL328094
10.51	Ki	0.031	nM	CHEMBL90700
10.50	Kd	0.03162	nM	UMECLIDINIUM BROMIDE
10.50	IC50	0.03162	nM	TIOTROPIUM BROMIDE
10.46	Kd	0.03467	nM	CHEMBL320611
10.41	EC50	0.039	nM	CHEMBL92421
10.40	Ki	0.04	nM	CHEMBL350956
10.35	Ki	0.045	nM	QUINUCLIDINYL BENZILATE
10.30	Kd	0.05012	nM	CHEMBL553448
10.30	Kd	0.05012	nM	CHEMBL2103803
10.30	ED50	0.05	nM	ATROPINE
10.29	Ki	0.051	nM	QUINUCLIDINYL BENZILATE
10.27	Ki	0.054	nM	CHEMBL320611
10.25	Ki	0.056	nM	CHEMBL1910848
10.24	Ki	0.057	nM	CHEMBL2115128
10.22	Ki	0.06	nM	CHEMBL556635
10.21	Ki	0.061	nM	TIOTROPIUM BROMIDE
10.20	Ki	0.0631	nM	METHSCOPOLAMINE
10.20	Ki	0.0631	nM	CHEMBL4582879
10.20	Ki	0.0631	nM	CHEMBL4540949
10.20	IC50	0.0631	nM	TIOTROPIUM BROMIDE
10.15	Ki	0.07	nM	CHEMBL308566
10.14	Ki	0.073	nM	CHEMBL94189
10.12	Ki	0.07586	nM	CHEMBL115078
10.10	Ki	0.07943	nM	CHEMBL4455570
10.10	Ki	0.07943	nM	CHEMBL4582879
10.10	Ki	0.07943	nM	CHEMBL4589047
10.10	Ki	0.07943	nM	CHEMBL4569639
10.10	Ki	0.07943	nM	CHEMBL4451383
10.10	Ki	0.07943	nM	CHEMBL4856113
10.10	Ki	0.08	nM	CHEMBL564057
10.10	Ki	0.08	nM	ACLIDINIUM BROMIDE
10.00	Ki	0.1	nM	CHEMBL352380
10.00	Ki	0.1	nM	CHEMBL167396
10.00	Ki	0.1	nM	CHEMBL164935
10.00	Ki	0.1	nM	CHEMBL352291
10.00	Ki	0.1	nM	CHEMBL2023764
10.00	Ki	0.1	nM	CHEMBL4597498
10.00	Kd	0.1	nM	CHEMBL4860528
10.00	Kd	0.1	nM	CHEMBL5207281
10.00	Kd	0.1	nM	CHEMBL5206565

PubChem BioAssay actives

2097 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
Tiotropium Bromide Monohydrate	1056125: Binding affinity to human M2 receptor	ki	<0.0001	uM
diphenyl-[1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-4-yl]methanol bromide	414952: Antagonist activity at human cloned muscarinic M2 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	631742: Displacement of [3H]NMS from recombinant human M2 receptor expressed in CHO-K1 cells after 16 hrs	ic50	<0.0001	uM
5-(1-azabicyclo[2.2.1]heptan-3-yl)-3-methyl-1,2,4-oxadiazole	142743: In vitro negative chronotropic effect on electrically driven guinea pig atria(mediated by Muscarinic M2 receptor)	ec50	<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
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
ethyl 4-[4-[(4R,5R)-2-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]-4,5-dimethyl-1,3-dioxolan-2-yl]piperidin-1-yl]piperidine-1-carboxylate	142936: Binding affinity at human cloned acetylcholine receptor M2 in CHO cells.	ki	<0.0001	uM
4-[2-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]-1,3-dithiolan-2-yl]-1-(1-propylsulfonylpiperidin-4-yl)piperidine	142936: Binding affinity at human cloned acetylcholine receptor M2 in CHO cells.	ki	<0.0001	uM
(2R)-1-[(1S)-1-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]ethyl]-4-cyclohexyl-2-methylpiperazine	142533: Binding affinity against human cloned Muscarinic acetylcholine receptor M2.	ki	<0.0001	uM
(2S)-1-cyclohexyl-4-[(1R)-1-[4-(4-methoxyphenyl)sulfonylphenyl]ethyl]-2-methylpiperazine	142533: Binding affinity against human cloned Muscarinic acetylcholine receptor M2.	ki	<0.0001	uM
(2R)-1-[(1R)-1-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]ethyl]-4-cyclohexyl-2-methylpiperazine	142533: Binding affinity against human cloned Muscarinic acetylcholine receptor M2.	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	430617: Displacement of [3H]NMS from human muscarinic M2 receptor expressed in CHOK1 cells by microplate scintillation counting	ic50	0.0001	uM
1-cyclohexyl-4-[1-[4-(4-methoxyphenyl)sulfinylphenyl]ethyl]piperidine	142534: Binding affinity against Muscarinic acetylcholine receptor M2	ki	0.0001	uM
benzyl (2S)-3-hydroxy-2-[[2-(tetradecanoylamino)acetyl]amino]propanoate	141245: Binding of [3H]QNB to HM2 receptor was evaluated by saturation binding assay	kd	0.0001	uM
1,3-benzodioxol-4-yl-[4-[(3R)-4-[(1S)-1-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]ethyl]-3-methylpiperazin-1-yl]piperidin-1-yl]methanone	142525: Binding affinity against human muscarinic acetylcholine receptor M2 using [3H]N-methylscopolamine as radioligand	ki	0.0001	uM
3-(8-hex-5-enyl-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl)-2,2-diphenylpropanenitrile bromide	658774: Displacement of [3H]-N-methyl scopolamine from muscarinic acetylcholine M2 receptor expressed in CHO cell membrane	ki	0.0001	uM
1-N,3-N-bis[2-[3-[1-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]imidazol-4-yl]propanoylamino]ethyl]-5-[(propanoylamino)methyl]benzene-1,3-dicarboxamide;tetrakis(2,2,2-trifluoroacetic acid)	1482282: Displacement of [3H]UNSW-MK259 from human muscarinic acetylcholine receptor M2 expressed in CHOK9 cells after 3 hrs by liquid scintillation counting assay	ki	0.0001	uM
ethyl 4-[4-[4-(1,3-benzodioxol-5-ylsulfonyl)benzoyl]piperidin-1-yl]piperidine-1-carboxylate	142936: Binding affinity at human cloned acetylcholine receptor M2 in CHO cells.	ki	0.0001	uM
ethyl 4-[4-[2-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]-1,3-dioxolan-2-yl]piperidin-1-yl]piperidine-1-carboxylate	142936: Binding affinity at human cloned acetylcholine receptor M2 in CHO cells.	ki	0.0001	uM
ethyl 4-[4-[2-[4-(4-methoxyphenyl)sulfonylphenyl]-1,3-dithiolan-2-yl]piperidin-1-yl]piperidine-1-carboxylate	142936: Binding affinity at human cloned acetylcholine receptor M2 in CHO cells.	ki	0.0001	uM
(2R)-4-cyclohexyl-1-[(1R)-1-[4-(4-methoxyphenyl)sulfonylphenyl]ethyl]-2-methylpiperazine	142533: Binding affinity against human cloned Muscarinic acetylcholine receptor M2.	ki	0.0001	uM
(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-6-amino-N-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethyl]hexanamide;tetrakis(2,2,2-trifluoroacetic acid)	1598792: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method	ki	0.0001	uM
(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-3-(4-hydroxyphenyl)-N-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethyl]propanamide;tris(2,2,2-trifluoroacetic acid)	1598792: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method	ki	0.0001	uM
11-[2-[4-[4-[4-[3-[[4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-1,2,5-thiadiazol-3-yl]oxy]propyl]piperazin-1-yl]butyl]piperidin-1-yl]acetyl]-5H-benzo[b][1,4]benzodiazepin-6-one	1598792: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method	ki	0.0001	uM
(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]-6-amino-N-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethyl]hexanamide;tetrakis(2,2,2-trifluoroacetic acid)	1598792: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method	ki	0.0001	uM
[1-[3-(4-chlorophenyl)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate bromide	1591564: Displacement of [3H]NMS from human M2R expressed in CHOK1 cell membranes incubated for 2 hrs by microbeta scintillation counting method	ki	0.0001	uM
(2S)-2-acetamido-6-amino-N-[(2S)-3-(4-hydroxyphenyl)-1-oxo-1-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethylamino]propan-2-yl]hexanamide;tetrakis(2,2,2-trifluoroacetic acid)	1598792: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method	ki	0.0001	uM
(2S)-2-acetamido-6-amino-N-[(2S)-5-(diaminomethylideneamino)-1-oxo-1-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethylamino]pentan-2-yl]hexanamide;pentakis(2,2,2-trifluoroacetic acid)	1598792: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method	ki	0.0001	uM
(2S)-2-acetamido-6-amino-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethylamino]pentan-2-yl]amino]-1-oxopropan-2-yl]hexanamide;pentakis(2,2,2-trifluoroacetic acid)	1598792: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method	ki	0.0001	uM
(2S)-2-acetamido-6-amino-N-[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxo-1-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethylamino]pentan-2-yl]amino]-1-oxopropan-2-yl]hexanamide	1756787: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis	ki	0.0001	uM
(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)-N-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethyl]propanamide;tris(2,2,2-trifluoroacetic acid)	1598792: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method	ki	0.0001	uM
5-methyl-5-(3-phenoxyazetidin-1-yl)-2,2-diphenylhexanamide	627016: Displacement of [3H]-NMS from human recombinant M2 receptor expressed in CHO cells after 2 hrs by filter binding assay	ki	0.0001	uM
5-[3-(3-hydroxyphenoxy)azetidin-1-yl]-5-methyl-2,2-diphenylhexanamide	627079: Displacement of [3H]-NMS from human recombinant M2 receptor expressed in CHO cells after 24 hrs by filter binding assay	ki	0.0001	uM
(2S)-2-acetamido-5-amino-N-[(2S)-2-[[(2S)-4-(diaminomethylideneamino)-2-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethylamino]butanoyl]amino]propanoyl]pentanamide;pentakis(2,2,2-trifluoroacetic acid)	1756787: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis	ki	0.0001	uM
1-[N’-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]carbamimidoyl]-3-pentylurea	1895228: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M2 receptor stably expressed in CHO cells by radioligand competition binding based analysis	kd	0.0001	uM
(2S)-2,5-diamino-N-[(2S)-2-[[(2S)-5-(diaminomethylideneamino)-2-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethylamino]pentanoyl]amino]propanoyl]pentanamide;pentakis(2,2,2-trifluoroacetic acid)	1756787: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis	ki	0.0001	uM
(2S)-2-amino-5-(diaminomethylideneamino)-N-[2-[4-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperazin-1-yl]ethyl]pentanamide;pentakis(2,2,2-trifluoroacetic acid)	1756787: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis	ki	0.0001	uM
(2R)-5-(diaminomethylideneamino)-2-[[1-[4-[1-[2-oxo-2-(6-oxo-5H-benzo[b][1,4]benzodiazepin-11-yl)ethyl]piperidin-4-yl]butyl]piperidin-4-yl]amino]pentanoic acid;tetrakis(2,2,2-trifluoroacetic acid)	1756787: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis	ki	0.0001	uM
1-[(1R)-1-phenylethyl]-3-[N’-[3-(1H-1,2,4-triazol-5-yl)propyl]carbamimidoyl]urea;dihydrochloride	1895228: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M2 receptor stably expressed in CHO cells by radioligand competition binding based analysis	kd	0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-pentylurea;bis(2,2,2-trifluoroacetic acid)	1895228: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M2 receptor stably expressed in CHO cells by radioligand competition binding based analysis	kd	0.0001	uM
1-[N’-[3-(5-amino-1,3,4-thiadiazol-2-yl)propyl]carbamimidoyl]-3-benzylurea;bis(2,2,2-trifluoroacetic acid)	1895228: Displacement of [3H]N-methylscopolamine from human muscarinic acetylcholine M2 receptor stably expressed in CHO cells by radioligand competition binding based analysis	kd	0.0001	uM
[(3R)-1-(2-phenylethyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate bromide	430623: Binding affinity to muscarinic M2 receptor	ki	0.0001	uM
[4-[4-[2-[4-(4-methoxyphenyl)sulfonylphenyl]-1,3-dioxolan-2-yl]piperidin-1-yl]piperidin-1-yl]-naphthalen-1-ylmethanone	142513: Antagonistic activity against muscarinic acetylcholine receptor M2	ki	0.0001	uM
(2R)-1-cyclohexyl-4-[(1R)-1-[4-(4-methoxyphenyl)sulfonylphenyl]ethyl]-2-methylpiperazine	142533: Binding affinity against human cloned Muscarinic acetylcholine receptor M2.	ki	0.0001	uM
[4-[(3R)-4-[(1S)-1-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]ethyl]-3-methylpiperazin-1-yl]piperidin-1-yl]-(2-methoxyphenyl)methanone	142525: Binding affinity against human muscarinic acetylcholine receptor M2 using [3H]N-methylscopolamine as radioligand	ki	0.0001	uM
[4-[(3R)-4-[(1S)-1-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]ethyl]-3-methylpiperazin-1-yl]piperidin-1-yl]-(2-chlorophenyl)methanone	142525: Binding affinity against human muscarinic acetylcholine receptor M2 using [3H]N-methylscopolamine as radioligand	ki	0.0001	uM
[4-[(3R)-4-[(1S)-1-[4-(1,3-benzodioxol-5-ylsulfonyl)phenyl]ethyl]-3-methylpiperazin-1-yl]piperidin-1-yl]-(2-phenoxyphenyl)methanone	142525: Binding affinity against human muscarinic acetylcholine receptor M2 using [3H]N-methylscopolamine as radioligand	ki	0.0001	uM
[(2S)-3-oxo-3-phenylmethoxy-2-[[2-(tetradecanoylamino)acetyl]amino]propyl] hexadecanoate	141247: Ability to displace [3H]QNB from HM2 receptor binding to acetylcholine was evaluated by ligand inhibition assay	ki	0.0002	uM
3-[(3R)-3-methoxy-1-azabicyclo[2.2.2]octan-3-yl]-1,1-dithiophen-2-ylprop-2-yn-1-ol	258309: Binding affinity to human muscarinic M2 receptor	ki	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
N-Methylscopolamine	decreases reaction, affects binding, affects reaction, increases reaction	9
brucine	affects reaction, increases reaction, affects binding	3
Acetylcholine	decreases reaction, affects binding, increases activity, affects reaction, increases reaction	3
Gallamine Triethiodide	increases reaction, decreases reaction, affects binding, affects reaction	3
N-chloromethylbrucine	increases reaction, decreases reaction, increases activity, affects binding	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Chlorpyrifos	affects binding, decreases reaction, increases expression	2
Pilocarpine	affects binding, increases reaction, increases expression	2
Scopolamine Derivatives	affects binding, decreases reaction	2
Strychnine	affects binding, increases reaction	2
omadacycline	affects binding	1
oxybutynin	decreases activity, affects binding	1
bisphenol A	increases expression	1
caracurine	affects binding	1
5-methylfurtrethonium	affects binding, increases reaction	1
eburnamonine	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
furtrethonium	affects binding, increases reaction	1
4-diphenylacetoxy-1,1-dimethylpiperidinium	affects binding, decreases reaction	1
oxotremorine M	affects binding, increases reaction	1
methoctramine	affects binding, decreases reaction	1
KT 5720	affects binding, increases reaction	1
KT 5823	affects binding, increases reaction	1
brucine N-oxide	increases reaction, affects binding	1
CGP 52608	affects binding, increases reaction	1
darifenacin	affects binding, decreases activity	1
dimethyl-W84	affects binding, affects reaction	1
bardoxolone methyl	decreases activity	1
5-(3-(3-hydroxyphenoxy)azetidin-1-yl)-5-methyl-2,2-diphenylhexanamide	affects binding	1
Tolterodine Tartrate	affects binding, decreases activity	1

ChEMBL screening assays

1316 unique, capped per target: 958 binding, 339 functional, 17 admet, 1 unclassified, 1 toxicity

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

9 cell lines: 6 spontaneously immortalized cell line, 2 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_E3RN	BIHi005-A-39	Induced pluripotent stem cell	Male
CVCL_F2AY	CHO-K1 hm2	Spontaneously immortalized cell line	Female
CVCL_H455	CHO-K1/M2/Galpha15	Spontaneously immortalized cell line	Female
CVCL_KU92	cAMP Hunter CHO-K1 CHRM2 Gs	Spontaneously immortalized cell line	Female
CVCL_KW68	PathHunter CHO-K1 CHRM2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA02	PathHunter U2OS CHRM2 Activated GPCR Internalization	Cancer cell line	Female
CVCL_RQ17	ValiScreen human CHRM2	Spontaneously immortalized cell line	Female
CVCL_U003	CHO-CHRM2	Spontaneously immortalized cell line	Female
CVCL_ZK05	Tango CHRM2-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	PHASE3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	PHASE3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	PHASE3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	PHASE3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
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