ACHE

Summary

ACHE (acetylcholinesterase (Yt blood group), HGNC:108) is a protein-coding gene on chromosome 7q22.1, encoding Acetylcholinesterase (P22303). Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction.

Acetylcholinesterase hydrolyzes the neurotransmitter, acetylcholine at neuromuscular junctions and brain cholinergic synapses, and thus terminates signal transmission. It is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen. Acetylcholinesterase exists in multiple molecular forms which possess similar catalytic properties, but differ in their oligomeric assembly and mode of cell attachment to the cell surface. It is encoded by the single ACHE gene, and the structural diversity in the gene products arises from alternative mRNA splicing, and post-translational associations of catalytic and structural subunits. The major form of acetylcholinesterase found in brain, muscle and other tissues is the hydrophilic species, which forms disulfide-linked oligomers with collagenous, or lipid-containing structural subunits. The other, alternatively spliced form, expressed primarily in the erythroid tissues, differs at the C-terminal end, and contains a cleavable hydrophobic peptide with a GPI-anchor site. It associates with the membranes through the phosphoinositide (PI) moieties added post-translationally. AChE activity may constitute a sensitive biomarker of RBC ageing in vivo, and thus, may be of aid in understanding the effects of transfusion

Source: NCBI Gene 43 — RefSeq curated summary.

At a glance

• GWAS associations: 35
• Clinical variants (ClinVar): 82 total — 5 pathogenic
• Druggable target: yes — 153 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000665

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:108
Approved symbol	ACHE
Name	acetylcholinesterase (Yt blood group)
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000087085
Ensembl biotype	protein_coding
OMIM	100740
Entrez	43

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 24 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000241069, ENST00000302913, ENST00000411582, ENST00000412389, ENST00000419336, ENST00000426415, ENST00000428317, ENST00000430554, ENST00000440755, ENST00000441605, ENST00000442452, ENST00000445236, ENST00000454485, ENST00000651875, ENST00000894903, ENST00000894904, ENST00000894905, ENST00000894906, ENST00000894907, ENST00000894908, ENST00000894909, ENST00000894910, ENST00000894911, ENST00000932266, ENST00000932267, ENST00000956361, ENST00000956362, ENST00000956363

RefSeq mRNA: 8 — MANE Select: NM_000665 NM_000665, NM_001282449, NM_001302621, NM_001302622, NM_001367915, NM_001367917, NM_001367918, NM_001367919

CCDS: CCDS5709, CCDS5710, CCDS64736

Canonical transcript exons

ENST00000241069 — 5 exons

Exon	Start	End
ENSE00001639836	100889994	100890335
ENSE00001873556	100895802	100895888
ENSE00002523632	100893165	100894252
ENSE00002524107	100892334	100892818
ENSE00003568040	100891169	100891338

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 95.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4021 / max 182.5674, expressed in 916 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85253	6.1941	887
85257	0.5404	109
85254	0.3379	127
85252	0.1949	78
85255	0.1348	72

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	95.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.30	gold quality
cerebellar hemisphere	UBERON:0002245	94.16	gold quality
cerebellar cortex	UBERON:0002129	93.98	gold quality
hypothalamus	UBERON:0001898	92.58	gold quality
cerebellum	UBERON:0002037	91.78	gold quality
gastrocnemius	UBERON:0001388	89.72	gold quality
nucleus accumbens	UBERON:0001882	89.30	gold quality
muscle of leg	UBERON:0001383	88.94	gold quality
triceps brachii	UBERON:0001509	88.68	gold quality
muscle organ	UBERON:0001630	88.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.97	gold quality
right frontal lobe	UBERON:0002810	87.87	gold quality
skeletal muscle tissue	UBERON:0001134	87.49	gold quality
putamen	UBERON:0001874	87.18	gold quality
caudate nucleus	UBERON:0001873	87.15	gold quality
biceps brachii	UBERON:0001507	86.41	gold quality
prefrontal cortex	UBERON:0000451	86.15	gold quality
cingulate cortex	UBERON:0003027	85.85	gold quality
anterior cingulate cortex	UBERON:0009835	85.75	gold quality
pons	UBERON:0000988	85.54	gold quality
substantia nigra pars compacta	UBERON:0001965	85.39	gold quality
substantia nigra	UBERON:0002038	85.37	gold quality
quadriceps femoris	UBERON:0001377	85.18	silver quality
vastus lateralis	UBERON:0001379	85.13	silver quality
midbrain	UBERON:0001891	84.60	gold quality
substantia nigra pars reticulata	UBERON:0001966	84.50	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.09	gold quality
muscle tissue	UBERON:0002385	83.93	gold quality
superior vestibular nucleus	UBERON:0007227	83.89	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	371.79
E-MTAB-8498	yes	112.33
E-HCAD-25	yes	9.38
E-ANND-3	no	1.51

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ASCL1, ATF1, ATF2, CEBPB, CREB1, CTBP2, DIDO1, DLX4, E4F1, EBF1, EGR1, ELK3, ESR1, FOS, FOXC1, GABPA, GRHL3, HR, IRF1, JUN, KLF12, LITAF, MYC, MYOD1, MYOG, MYT1, NCOR1, NCOR2, NFATC1, NFATC3, NFATC4, NFE2L2, NFKB1, NKX3-1, RARB, SMAD3, SOX17

Literature-anchored findings (GeneRIF, showing 40)

• Generation of a gp43-gp59-DNA ternary complex is absolutely required for recombination-dependent replication in the bacteriophage T4 system. (PMID:15909989)
• the primer strand is not stably bound within the exonuclease active site in the absence of the beta hairpin loop (PMID:17098747)
• The authors propose that their beta loops facilitate strand separation, while the residues that form the loop have low structural constraints. (PMID:19409904)
• Amino acid substitutions that confer decreased ability to replicate DNA under low-dGTP conditions or drug sensitivity were identified in the new motif, which suggests that the motif functions in regulating the stability of polymerase complexes. (PMID:20493878)
• Data describe the crystal structures of the pol alpha family RB69 DNA polymerase with DNA containing the two most prevalent, spontaneously generated premutagenic lesions (PMID:15057282)
• Results describe the structure of the bacteriophage RB69 replicative DNA polymerase attempting to process an abasic site analog. (PMID:15057283)
• the primer strand is not stably bound within the exonuclease active site in the absence of the beta hairpin loop (PMID:17098747)
• The Y619F substitution would disrupt the hydrogen bond network at the primer terminus and may affect the alignment of the 3’ primer terminus at the polymerase active site, slowing chemistry and overall DNA synthesis. (PMID:17321543)
• Binding of a metal ion to the A site is required for the nucleotidyl transfer reaction, but is insufficient to initiate the enzyme isomerization. Binding of a dNTP, in the absence of a metal ion, is sufficient to induce this conformational change. (PMID:19228036)
• The effect of A and B metal ion site occupancy on the rates of Fingers closing and on the affinity of Rh.dTTP for the E.D binary complex of the catalytic site of RB69 DNA polymerase was studied. (PMID:19228037)
• The authors propose that their beta loops facilitate strand separation, while the residues that form the loop have low structural constraints. (PMID:19409904)
• When Y567A and S565G replacements were combined, mutator activity was strongly decreased compared to that with Y567A replacement alone. (PMID:20950625)
• The structure of an RB69 pol ternary complex at 1.8 A is reported. A network of five highly ordered, buried water molecules can be seen to interact with the N3 and O2 atoms in the minor groove of the DNA duplex. (PMID:21158418)
• The authors show that the S565G/Y567A mutant generally had greater base selectivity than the Y567A mutant and that the kinetic parameters for dNMP insertion, excision of the 3’-terminal nucleotide residue, and primer extension beyond a mispair differed. (PMID:21216248)
• The miscoding potential of 5-hydroxycytosine arises due to template instability in the DNA polymerase active site. (PMID:22026756)
• evaluated the contribution of minor groove hydrogen bonding interactions with RB69pol (PMID:22571765)
• Determined is the crystal structure of the dATP/tC(o)-containing ternary complex of the RB69 DNA polymerase Y567A mutant at 1.9 A resolution; the incoming dATP formed two hydrogen bonds with an imino-tautomerized form of tC(o). (PMID:22616982)
• Data indicate that alanine replacement of residues distant from the active site of the replicative RB69 DNA polymerase renders the enzyme incapable of sustaining phage replication in vivo. (PMID:24116139)
• structures of the various RB69pol ternary complexes can be used to rationalize the results obtained from pre-steady-state kinetic assays[review] (PMID:24720884)
• Co(2+) and Mn(2+) enhanced ground-state binding of both correct and incorrect dNTPs to RB69pol:dideoxy-terminated primer-template complexes. (PMID:27096230)
• The control of the discrimination between dNTP and rNTP in DNA and RNA polymerases has been described. (PMID:27480935)
• serum and erythrocyte membrane enzyme inhibited by antidepressants, fluoxetine, sertraline and amitriptyline, in a dose related manner (PMID:12009429)
• REVIEW: Simulations show how breathing motions in the enzyme facilitate the displacement of substrate from the surface of the enzyme to the buried active site; such motions suggest possible modes of regulation of the activity of the enzyme. (PMID:12069617)
• The aromatic “trapping” of the catalytic histidine is essential for efficient catalysis (PMID:12081473)
• regulation of ACHE expression in developing muscle cells (PMID:12140295)
• complex regulation of its gene expression in brain tumors (PMID:12466963)
• AChE activity in the CSF of Alzeimer’s disease patients is affected differentially by different AChE inhibitors. (AChE) (PMID:12548360)
• AChE was predominantly expressed in neurons of the anterodorsal, midline, ventral, intralaminar, and reticular nuclei. (PMID:12811800)
• analysis of acetylcholinesterase active site (PMID:12851386)
• muscle-induced neuronal AChE expression in co-culture is mediated by a cAMP-dependent signaling (PMID:12963741)
• oxidation of AchE by hydrogen peroxide contributes significantly to the well-established oxidative stress in vitiligo (PMID:14766237)
• analysis of acetylcholinesterase near the active center gorge (PMID:15078872)
• Data suggest that alternative promoter usage combined with alternative splicing may lead to stress-dependent combinatorial complexity of acetylcholinesterase mRNA transcripts and their protein products. (PMID:15123727)
• complexed with abeta protein, is toxic to rat brain beta-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss. (PMID:15161650)
• AChE is involved in regulating cell-matrix interactions in bone (PMID:15454088)
• A total of 13 ACHE SNPs were identified, 10 of which are newly described, and five that should produce amino acid substitutions (PMID:15459952)
• This study found a layer 3 magnopyramidal AChERN left-right size asymmetry restricted to Brodmann’s area 45, a component of Broca’s language area. (PMID:15488495)
• findings suggest that inherited interactive weakness of acetylcholinesterase and paraoxonase 1 expression increases the insecticide-induced occurrence of Parkinson’s disease (PMID:15629887)
• Variations were observed in expression of mRNA for presenilin-1, which was highest in singly transgenic hAChE mice, and the stress-inducible form of AChE, which was elevated when both transgenes were present. (PMID:15974894)
• Human plasma contains four esterases: butyrylcholinesterase, paraoxonase, acetylcholinesterase, and albumin. (PMID:16213467)

Cross-species orthologs

45 orthologs

Organism	Symbol	Gene ID
danio_rerio	ache	ENSDARG00000031796
mus_musculus	Ache	ENSMUSG00000023328
rattus_norvegicus	Ache	ENSRNOG00000050841
drosophila_melanogaster	Est-6	FBGN0000592
drosophila_melanogaster	Est-P	FBGN0000594
drosophila_melanogaster	Glt	FBGN0001114
drosophila_melanogaster	Jhe	FBGN0010052
drosophila_melanogaster	alpha-Est1	FBGN0015568
drosophila_melanogaster	alpha-Est10	FBGN0015569
drosophila_melanogaster	alpha-Est2	FBGN0015570
drosophila_melanogaster	alpha-Est3	FBGN0015571
drosophila_melanogaster	alpha-Est4	FBGN0015572
drosophila_melanogaster	alpha-Est6	FBGN0015574
drosophila_melanogaster	alpha-Est7	FBGN0015575
drosophila_melanogaster	alpha-Est8	FBGN0015576
drosophila_melanogaster	alpha-Est9	FBGN0015577
drosophila_melanogaster	CG4757	FBGN0027584
drosophila_melanogaster	CG9287	FBGN0032057
drosophila_melanogaster	CG9289	FBGN0032058
drosophila_melanogaster	CG3841	FBGN0032131
drosophila_melanogaster	CG4382	FBGN0032132
drosophila_melanogaster	Jhedup	FBGN0034076
drosophila_melanogaster	gas	FBGN0034736
drosophila_melanogaster	alpha-Est5	FBGN0261393
caenorhabditis_elegans		WBGENE00000037
caenorhabditis_elegans		WBGENE00000038
caenorhabditis_elegans		WBGENE00007691
caenorhabditis_elegans		WBGENE00007692
caenorhabditis_elegans		WBGENE00007693
caenorhabditis_elegans		WBGENE00007695
caenorhabditis_elegans		WBGENE00008451
caenorhabditis_elegans		WBGENE00011362
caenorhabditis_elegans		WBGENE00011364
caenorhabditis_elegans		WBGENE00013873
caenorhabditis_elegans		WBGENE00013874
caenorhabditis_elegans		WBGENE00013875
caenorhabditis_elegans		WBGENE00015067
caenorhabditis_elegans		WBGENE00015071
caenorhabditis_elegans		WBGENE00015279
caenorhabditis_elegans		WBGENE00015284
caenorhabditis_elegans		WBGENE00016595
caenorhabditis_elegans		WBGENE00016862
caenorhabditis_elegans		WBGENE00016863
caenorhabditis_elegans	cest-27	WBGENE00018958
caenorhabditis_elegans		WBGENE00020688

Paralogs (13): TG (ENSG00000042832), BCHE (ENSG00000114200), NLGN4X (ENSG00000146938), CES5A (ENSG00000159398), NLGN4Y (ENSG00000165246), NLGN1 (ENSG00000169760), NLGN2 (ENSG00000169992), CEL (ENSG00000170835), CES4A (ENSG00000172824), CES3 (ENSG00000172828), CES2 (ENSG00000172831), NLGN3 (ENSG00000196338), CES1 (ENSG00000198848)

Protein

Protein identifiers

Acetylcholinesterase — P22303 (reviewed: P22303)

All UniProt accessions (8): P22303, A0A498U6H7, C9J2S3, C9JD78, C9JZL6, F8WAR7, F8WD34, F8WD68

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis.

Subunit / interactions. Interacts with PRIMA1. The interaction with PRIMA1 is required to anchor it to the basal lamina of cells and organize into tetramers. Isoform H generates GPI-anchored dimers; disulfide linked. Isoform T generates multiple structures, ranging from monomers and dimers to collagen-tailed and hydrophobic-tailed forms, in which catalytic tetramers are associated with anchoring proteins that attach them to the basal lamina or to cell membranes. In the collagen-tailed forms, isoform T subunits are associated with a specific collagen, COLQ, which triggers the formation of isoform T tetramers, from monomers and dimers. Isoform R may be monomeric.

Subcellular location. Synapse. Secreted. Cell membrane Nucleus Cell membrane.

Tissue specificity. Isoform H is highly expressed in erythrocytes.

Polymorphism. ACHE is responsible for the Yt blood group system [MIM:112100]. The molecular basis of the Yt(a)=Yt1/Yt(b)=Yt2 blood group antigens is a single variation in position 353; His-353 corresponds to Yt(a) and the rare variant with Asn-353 to Yt(b).

Similarity. Belongs to the type-B carboxylesterase/lipase family.

Isoforms (4)

UniProt ID	Names	Canonical?
P22303-1	T, ACHE-S, synaptic	yes
P22303-2	H, ACHE-E, erythrocytic, E4-E5
P22303-4	R, ACHE-R, readthrough
P22303-3	4

RefSeq proteins (8): NP_000656, NP_001269378, NP_001289550, NP_001289551, NP_001354844, NP_001354846, NP_001354847, NP_001354848 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000997	Cholinesterase	Family
IPR002018	CarbesteraseB	Domain
IPR014788	AChE_tetra	Domain
IPR019819	Carboxylesterase_B_CS	Conserved_site
IPR019826	Carboxylesterase_B_AS	Active_site
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR050654	AChE-related_enzymes	Family

Pfam: PF00135, PF08674

Enzyme classification (BRENDA):

• EC 3.1.1.7 — acetylcholinesterase (BRENDA: 125 organisms, 230 substrates, 2038 inhibitors, 343 Km, 72 kcat entries)
• EC 3.5.1.13 — aryl-acylamidase (BRENDA: 52 organisms, 138 substrates, 181 inhibitors, 55 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

64 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETYLTHIOCHOLINE	0.0062–34	131
ACETYLTHIOCHOLINE IODIDE	0.0002–5.8	42
ACETYLCHOLINE	0.0001–2.36	38
PROPIONYLTHIOCHOLINE	0.006–27.912	37
BUTYRYLTHIOCHOLINE	0.0029–5.14	33
3’,4’-DICHLOROPROPIONANILIDE	0.02–25	14
BUTYRYLTHIOCHOLINE IODIDE	0.0004–0.59	5
PROPIONYLTHIOCHOLINE IODIDE	0.0005–0.42	5
P-NITROACETANILIDE	0.012–0.07	4
ACETYL-BETA-METHYLTHIOCHOLINE	0.014–0.2206	3
ACETANILIDE	0.15–19	3
ACETYLCHOLINE IODIDE	0.0123–0.1065	2
BUTANOYLTHIOCHOLINE	1.15–1.7	2
BUTYLTHIOCHOLINE	0.67–1.69	2
METHYLTHIOCHOLINE	2.23–2.45	2

Catalyzed reactions (Rhea), 1 shown:

• acetylcholine + H2O = choline + acetate + H(+) (RHEA:17561)

UniProt features (100 total): helix 27, strand 26, binding site 10, mutagenesis site 6, turn 6, disulfide bond 4, splice variant 4, sequence variant 4, sequence conflict 4, glycosylation site 3, active site 3, signal peptide 1, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

79 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4M0E	X-RAY DIFFRACTION	2
6NTO	X-RAY DIFFRACTION	2.05
6O69	X-RAY DIFFRACTION	2.08
5HF5	X-RAY DIFFRACTION	2.15
6O5V	X-RAY DIFFRACTION	2.15
4EY4	X-RAY DIFFRACTION	2.16
6WVO	X-RAY DIFFRACTION	2.19
5HF9	X-RAY DIFFRACTION	2.2
5HFA	X-RAY DIFFRACTION	2.2
8DT7	X-RAY DIFFRACTION	2.21
6CQZ	X-RAY DIFFRACTION	2.22
6NTL	X-RAY DIFFRACTION	2.25
6U37	X-RAY DIFFRACTION	2.25
6WUZ	X-RAY DIFFRACTION	2.25
6CQT	X-RAY DIFFRACTION	2.27
6CQW	X-RAY DIFFRACTION	2.28
6WVQ	X-RAY DIFFRACTION	2.29
5FOQ	X-RAY DIFFRACTION	2.3
5HF6	X-RAY DIFFRACTION	2.3
6O4X	X-RAY DIFFRACTION	2.3
4EY5	X-RAY DIFFRACTION	2.3
4M0F	X-RAY DIFFRACTION	2.3
6CQU	X-RAY DIFFRACTION	2.31
6WVP	X-RAY DIFFRACTION	2.31
1VZJ	X-RAY DIFFRACTION	2.35
6O4W	X-RAY DIFFRACTION	2.35
4EY7	X-RAY DIFFRACTION	2.35
6O50	X-RAY DIFFRACTION	2.35
6WV1	X-RAY DIFFRACTION	2.37
4EY6	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22303-F1	93.04	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 234 (acyl-ester intermediate); 365 (charge relay system); 478 (charge relay system)

Ligand- & substrate-binding residues (10): 234; 368; 368; 470; 478; 117; 117; 153; 164; 233–234

Post-translational modifications (1): 588

Disulfide bonds (4): 100–127, 288–303, 440–560, 611

Glycosylation sites (3): 296, 381, 495

Mutagenesis-validated functional residues (6):

Position	Phenotype
206	misfolding, absence of secretion.
234	loss of activity.
365	loss of activity.
435	misfolding, absence of secretion.
478	loss of activity.
611	impairment of interchain disulfide bridge formation.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-112311	Neurotransmitter clearance
R-HSA-1483191	Synthesis of PC
R-HSA-422085	Synthesis, secretion, and deacylation of Ghrelin
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1430728	Metabolism
R-HSA-1483206	Glycerophospholipid biosynthesis
R-HSA-1483257	Phospholipid metabolism
R-HSA-2980736	Peptide hormone metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 0 (showing top):

GO Biological Process (14): acetylcholine catabolic process in synaptic cleft (GO:0001507), regulation of receptor recycling (GO:0001919), osteoblast development (GO:0002076), acetylcholine catabolic process (GO:0006581), cell adhesion (GO:0007155), nervous system development (GO:0007399), synapse assembly (GO:0007416), receptor internalization (GO:0031623), negative regulation of synaptic transmission, cholinergic (GO:0032223), amyloid precursor protein metabolic process (GO:0042982), positive regulation of protein secretion (GO:0050714), retina development in camera-type eye (GO:0060041), acetylcholine receptor signaling pathway (GO:0095500), positive regulation of cold-induced thermogenesis (GO:0120162)

GO Molecular Function (12): amyloid-beta binding (GO:0001540), acetylcholinesterase activity (GO:0003990), cholinesterase activity (GO:0004104), collagen binding (GO:0005518), hydrolase activity (GO:0016787), serine hydrolase activity (GO:0017171), acetylcholine binding (GO:0042166), protein homodimerization activity (GO:0042803), laminin binding (GO:0043236), protein binding (GO:0005515), identical protein binding (GO:0042802), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (13): extracellular region (GO:0005576), basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), neuromuscular junction (GO:0031594), synaptic cleft (GO:0043083), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Transmission across Chemical Synapses	1
Glycerophospholipid biosynthesis	1
Peptide hormone metabolism	1
Neuronal System	1
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism of proteins	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
synaptic transmission, cholinergic	2
protein binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
membrane	2
acetylcholine catabolic process	1
synaptic cleft	1
receptor recycling	1
regulation of signaling	1
regulation of macromolecule metabolic process	1
osteoblast differentiation	1
cell development	1
acetylcholine metabolic process	1
catabolic process	1
cellular process	1
system development	1
nervous system development	1
cell junction assembly	1
synapse organization	1
receptor-mediated endocytosis	1
regulation of synaptic transmission, cholinergic	1
negative regulation of synaptic transmission	1
protein metabolic process	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
camera-type eye development	1
anatomical structure development	1
acetylcholine receptor activity	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
peptide binding	1
cholinesterase activity	1
carboxylic ester hydrolase activity	1
protein-containing complex binding	1

Protein interactions and networks

STRING

2582 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACHE	COLQ	Q9Y215	981
ACHE	CHAT	P28329	933
ACHE	MAOB	P27338	902
ACHE	HSPG2	P98160	882
ACHE	DOK7	Q18PE1	865
ACHE	MUSK	O15146	860
ACHE	PNPLA6	Q8IY17	848
ACHE	SLC18A3	Q16572	844
ACHE	BACE1	P56817	831
ACHE	AGRN	O00468	811
ACHE	MAPT	P10636	811
ACHE	SI	P14410	786
ACHE	MGAM	O43451	785
ACHE	APP	P05067	769
ACHE	APOE	P02649	755

IntAct

21 interactions, top by confidence:

A	B	Type	Score
ACHE	COLQ	psi-mi:“MI:0407”(direct interaction)	0.560
COLQ	ACHE	psi-mi:“MI:0407”(direct interaction)	0.560
ACHE	RACK1	psi-mi:“MI:0915”(physical association)	0.530
ACHE	ENO1	psi-mi:“MI:0915”(physical association)	0.530
ACHE	ENO1	psi-mi:“MI:0414”(enzymatic reaction)	0.530
ACHE	RACK1	psi-mi:“MI:0414”(enzymatic reaction)	0.530
	ENO1	psi-mi:“MI:0414”(enzymatic reaction)	0.440
	ACHE	psi-mi:“MI:0414”(enzymatic reaction)	0.440
	ACHE	psi-mi:“MI:0407”(direct interaction)	0.440
ACHE	ACHE	psi-mi:“MI:0407”(direct interaction)	0.440
Rack1	ACHE	psi-mi:“MI:0915”(physical association)	0.400
ACHE	Eno1	psi-mi:“MI:0915”(physical association)	0.400
	ACHE	psi-mi:“MI:0915”(physical association)	0.400
GPC3	PXDNL	psi-mi:“MI:0914”(association)	0.350
ACHE	ATF7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (3): COL4A1 (Reconstituted Complex), ACHE (Reconstituted Complex), ACHE (Affinity Capture-RNA)

ESM2 similar proteins: A6NE02, A8MY62, A8T672, A8T677, A8T695, C9JR72, D3Z7H8, O08644, O15197, O19179, O62763, O94766, P0C0K6, P0C0K7, P21836, P22303, P24347, P35475, P50427, P51839, P51840, P52785, P54760, P55203, Q01634, Q02846, Q04912, Q29499, Q2KHV9, Q2T9T9, Q3UH93, Q5JZY3, Q69ZQ1, Q6NSJ0, Q6ZPS2, Q80W65, Q8BH02, Q8BYG9, Q8CG64, Q8IUL8

Diamond homologs: A0A443HK52, A0A8B0RBM2, A7YN26, B0F2B4, B2D0J5, D4B1N9, D6WMZ8, F1RRV3, I1RHF8, O08710, O16168, O16169, O16170, O16171, O16172, O16173, O42275, O62763, P01267, P04058, P06276, P06882, P07692, P07882, P08171, P10959, P12992, P17573, P18167, P19835, P20261, P21836, P21927, P22303, P22394, P23795, P25725, P25726, P25727, P30122

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
“Galanthamine hydrobromide”	down-regulates	ACHE	“chemical inhibition”
neostigmine	“down-regulates activity”	ACHE	“chemical inhibition”
4’-((2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)-[1,1’-biphenyl]-2-carbonitrile	“down-regulates activity”	ACHE	“chemical inhibition”
3-[(2-Bromo-4,5-dimethoxyphenyl)methyl]-2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one	“down-regulates activity”	ACHE	“chemical inhibition”
3-[(4-Bromophenyl)methyl]-2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one	“down-regulates activity”	ACHE	“chemical inhibition”
ACHE	“down-regulates quantity”	acetylcholine	“chemical modification”
Pyridostigmine	“down-regulates activity”	ACHE	“chemical inhibition”
pralidoxime	“up-regulates activity”	ACHE	“chemical activation”
edrophonium	“down-regulates activity”	ACHE	“chemical inhibition”
procainamide	“down-regulates activity”	ACHE	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	56
Likely benign	8
Benign	5

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
146501	GRCh38/hg38 7q22.1(chr7:99195836-102258175)x1	Pathogenic
4820055	NC_000007.14:g.99487704_102394107del	Pathogenic
59713	GRCh38/hg38 7q21.3-22.1(chr7:98288474-101259804)x3	Pathogenic
60280	GRCh38/hg38 7q22.1(chr7:99219420-100902269)x1	Pathogenic
60281	GRCh38/hg38 7q22.1(chr7:100419914-102482826)x1	Pathogenic

SpliceAI

992 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100891336:TCC:T	acceptor_gain	1.0000
7:100891337:CC:C	acceptor_gain	1.0000
7:100891337:CCC:C	acceptor_gain	1.0000
7:100891337:CCCT:C	acceptor_loss	1.0000
7:100891338:CC:C	acceptor_gain	1.0000
7:100891339:C:A	acceptor_loss	1.0000
7:100891339:C:CC	acceptor_gain	1.0000
7:100891340:T:C	acceptor_loss	1.0000
7:100892317:C:CA	donor_gain	1.0000
7:100892770:C:CT	acceptor_gain	1.0000
7:100892770:C:T	acceptor_gain	1.0000
7:100893160:GTTAC:G	donor_loss	1.0000
7:100893161:TTA:T	donor_loss	1.0000
7:100893162:TAC:T	donor_loss	1.0000
7:100893163:A:AT	donor_loss	1.0000
7:100895797:CTCA:C	donor_loss	1.0000
7:100895798:TCACC:T	donor_loss	1.0000
7:100895799:CACCT:C	donor_loss	1.0000
7:100890495:G:GC	acceptor_gain	0.9900
7:100891163:GCATA:G	donor_loss	0.9900
7:100891164:CATAC:C	donor_loss	0.9900
7:100891165:ATAC:A	donor_loss	0.9900
7:100891166:TA:T	donor_loss	0.9900
7:100891167:A:AC	donor_gain	0.9900
7:100891168:C:CC	donor_gain	0.9900
7:100891168:C:G	donor_loss	0.9900
7:100891334:GATCC:G	acceptor_gain	0.9900
7:100891335:ATCC:A	acceptor_gain	0.9900
7:100891342:C:CT	acceptor_gain	0.9900
7:100891343:G:T	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000084778 (7:100895649 A>C), RS1000529033 (7:100894767 A>G), RS1001224035 (7:100894919 G>C), RS1001371809 (7:100890193 G>A,C,T), RS1001781956 (7:100890465 G>A), RS1002167161 (7:100895863 C>T), RS1002220844 (7:100896291 T>G), RS1002502347 (7:100897646 T>C), RS1002551532 (7:100898019 C>T), RS1002660508 (7:100897085 C>T), RS1003155208 (7:100891475 G>T), RS1003332005 (7:100896141 TGACA>T), RS1003624235 (7:100896852 C>T), RS1003824943 (7:100890699 C>A,T), RS1003891856 (7:100892882 C>G)

Disease associations

OMIM: gene MIM:100740 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST001033_13	Type 2 diabetes	5.000000e-06
GCST001684_4	Plasminogen activator inhibitor type 1 levels (PAI-1)	6.000000e-13
GCST001969_9	Heart rate	8.000000e-27
GCST003818_36	Resting heart rate	1.000000e-41
GCST005788_14	Heart rate response to recovery post exercise	7.000000e-11
GCST005845_4	Heart rate increase in response to exercise	3.000000e-16
GCST005846_7	Heart rate response to recovery post exercise (10 sec)	6.000000e-21
GCST005847_9	Heart rate response to recovery post exercise (20 sec)	3.000000e-21
GCST005848_15	Heart rate response to recovery post exercise (50 sec)	4.000000e-23
GCST005849_14	Heart rate response to recovery post exercise (40 sec)	6.000000e-24
GCST005850_6	Heart rate response to recovery post exercise (30 sec)	8.000000e-23
GCST006979_144	Heel bone mineral density	3.000000e-12
GCST007096_237	Pulse pressure	4.000000e-10
GCST007250_7	Nonunion in individuals with fractures	3.000000e-07
GCST007268_34	Diastolic blood pressure	1.000000e-10
GCST008103_164	Bipolar disorder	7.000000e-06
GCST008129_64	Body mass index	3.000000e-10
GCST010083_136	Hemoglobin levels	1.000000e-09
GCST010796_3335	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_3336	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_3337	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_3338	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-09
GCST010796_3339	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3340	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3341	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_3342	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3343	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_3344	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_3345	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-10
GCST010796_5245	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-10

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004792	plasminogen activator inhibitor 1 measurement
EFO:0009185	heart rate response to recovery post exercise
EFO:0009184	heart rate response to exercise
EFO:0009270	heel bone mineral density
EFO:0005763	pulse pressure measurement
EFO:0009707	fractures, ununited
EFO:0006336	diastolic blood pressure
EFO:0004340	body mass index
EFO:0004509	hemoglobin measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095233 (SELECTIVITY GROUP), CHEMBL220 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

153 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 455,619 (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
CHEMBL1025	ISOFLUROPHATE	4	13,137
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1104	EDROPHONIUM	4	17,617
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1115	PYRIDOSTIGMINE	4	13,658
CHEMBL1128	EDROPHONIUM CHLORIDE	4	20,117
CHEMBL113	CAFFEINE	4	200,591
CHEMBL1134	DECAMETHONIUM BROMIDE	4	1,096
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL117287	PRUCALOPRIDE	4	2,516
CHEMBL119	TRIMETREXATE	4	57,002
CHEMBL1190	DECAMETHONIUM	4	1,139
CHEMBL1200623	ETHYLESTRENOL	4	1,795
CHEMBL1200970	ETHOPROPAZINE HYDROCHLORIDE	4	876
CHEMBL1201087	CABERGOLINE	4	12,778
CHEMBL1201092	RIVASTIGMINE TARTRATE	4	13
CHEMBL1201196	SERTACONAZOLE	4	9,003
CHEMBL1201217	DYCLONINE	4	7,785
CHEMBL1201256	TRIMETHOBENZAMIDE	4	6,347
CHEMBL1201349	HEXAFLUORENIUM	4	664
CHEMBL1206	ETHOPROPAZINE	4
CHEMBL1219	RABEPRAZOLE	4
CHEMBL1237021	LURASIDONE	4
CHEMBL1254682	LEVALLORPHAN	4
CHEMBL1262	OXICONAZOLE	4
CHEMBL1303	ROTIGOTINE	4
CHEMBL1372950	NICERGOLINE	4
CHEMBL142635	NAFTOPIDIL	4
CHEMBL14376	ILOPERIDONE	4
CHEMBL1493	FLAVOXATE	4

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2571598	Efficacy	3	rivastigmine	Alzheimer Disease

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2571598	ACHE	3	1.75	1	rivastigmine
rs6942609	ACHE		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Acetylcholine turnover

Most potent curated ligand interactions (16 total), top 16:

Ligand	Action	Affinity	Parameter
donepezil	Inhibition	8.3	pIC50
compound 2f [Jiang et al., 2018]	Inhibition	8.19	pIC50
apigenin	Inhibition	7.92	pIC50
donecopride	Inhibition	7.8	pIC50
physostigmine	Inhibition	7.8	pIC50
huperzine A	Inhibition	7.77	pKd
BW284C51	Inhibition	7.7	pIC50
tacrine	Inhibition	7.5	pKi
neostigmine	Inhibition	7.35	pIC50
edrophonium	Inhibition	6.7	pKi
pyridostigmine	Inhibition	6.44	pIC50
galantamine	Inhibition	6.3	pIC50
(-)-isatispironeol A	Inhibition	6.17	pIC50
AChE reactivator 2		5.64	pIC50
rivastigmine	Inhibition	5.4	pIC50
pralidoxime	Inhibition	3.1	pIC50

Binding affinities (BindingDB)

557 measured of 825 human assays (916 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(1S)-7-chloro-15-ethyl-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2(11),3,5,7,9,14-hexaen-3-amine	KI	0.026 nM
(+/-)-huprineY hydrochloride	KI	0.033 nM
methylbis[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]amine	KI	0.06 nM
N-(2-chlorobenzyl)-2-(2-(2-((2-chlorobenzyl)diethylammonio)ethylamino)-2-oxoacetamido)-N,N-diethylethanaminium	KI	0.12 nM
N-{3-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]propyl}-5-(1,2-dithiolan-3-yl)pentanamide	IC50	0.253 nM
{3-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]propyl}[3-({7-chloro-15-methyl-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2(11),3,5,7,9,14-hexaen-3-yl}amino)propyl]methylamine trihydrochloride	IC50	0.29 nM
3-{[methyl({3-[(9-oxo-9H-xanthen-3-yl)oxy]propyl})amino]methyl}phenyl N-methylcarbamate	IC50	0.3 nM
3-({7-chloro-15-methyl-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2(11),3,5,7,9,14-hexaen-3-yl}amino)propyl[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]amine trihydrochloride	IC50	0.32 nM
3-{[methyl({7-[(9-oxo-9H-xanthen-3-yl)oxy]heptyl})amino]methyl}phenyl N-methylcarbamate	IC50	0.32 nM
7-chloro-15-methyl-N-[8-(1,2,3,4-tetrahydroacridin-9-ylamino)octyl]-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2(11),3,5,7,9,14-hexaen-3-amine dihydrochloride	IC50	0.33 nM
3-Chloro-6,7,10,11-tetrahydro-9-methyl-12-{{7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]heptyl}amino}-7,11-methanocycloocta[b]quinoline dihydrochloride	IC50	0.33 nM
7-chloro-15-methyl-N-[7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptyl]-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2(11),3,5,7,9,14-hexaen-3-amine dihydrochloride	IC50	0.34 nM
3-Chloro-6,7,10,11-tetrahydro-9-methyl-12-{{8-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]octyl}amino}-7,11-methanocycloocta[b]quinoline dihydrochloride	IC50	0.4 nM
7-chloro-N-{6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]hexyl}-15-methyl-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2(11),3,5,7,9,14-hexaen-3-amine dihydrochloride	IC50	0.45 nM
7-chloro-15-methyl-N-[6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexyl]-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2(11),3,5,7,9,14-hexaen-3-amine dihydrochloride	IC50	0.5 nM
3-{[methyl(7-{[(2Z)-3-oxo-2-(3,4,5-trimethoxybenzylidene)-2,3-dihydro-1-benzofuran-6-yl]oxy}heptyl)amino]methyl}phenyl methylcarbamate	IC50	0.52 nM
3-{[ethyl({3-[(9-oxo-9H-xanthen-3-yl)oxy]propyl})amino]methyl}phenyl N-methylcarbamate	IC50	0.56 nM
2-{bis[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]amino}ethan-1-ol	KI	0.65 nM
3-[({3-[(9-oxo-9H-xanthen-3-yl)oxy]propyl}(propan-2-yl)amino)methyl]phenyl N-methylcarbamate	IC50	0.7 nM
CHEMBL4754487	IC50	0.77 nM
7-chloro-15-methyl-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2,4(9),5,7,10,14-hexaen-3-amine	IC50	0.78 nM
15-ethyl-N-[8-(1,2,3,4-tetrahydroacridin-9-ylamino)octyl]-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2(11),3,5,7,9,14-hexaen-3-amine dihydrochloride	IC50	0.82 nM
3-{[methyl({5-[(9-oxo-9H-xanthen-3-yl)oxy]pentyl})amino]methyl}phenyl N-methylcarbamate	IC50	0.82 nM
[1-(cyclohexylmethyl)piperidin-4-yl]methyl 4-amino-5-chloro-2-methoxybenzoate	KI	0.9 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
6,8-dichloro-1,2,3,4-tetrahydroacridin-9-amine	KI	1 nM
3-({methyl[3-({5-oxo-5H-chromeno[2,3-b]pyridin-8-yl}oxy)propyl]amino}methyl)phenyl N-methylcarbamate hydrochloride	IC50	1.1 nM
CHEMBL4744528	IC50	1.1 nM
[3-(2-acetamidoethyl)-1H-indol-5-yl] N-[10-(1,2,3,4-tetrahydroacridin-9-ylamino)decyl]carbamate	IC50	1.18 nM	US-8841453: Hybrid cholinesterase inhibitors
N-[7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptyl]-1,2,3,4-tetrahydroacridin-9-amine	KI	1.3 nM
3-{[methyl({6-[(9-oxo-9H-xanthen-3-yl)oxy]hexyl})amino]methyl}phenyl N-methylcarbamate	IC50	1.4 nM
[3-(2-acetamidoethyl)-1H-indol-5-yl] N-[10-[(7-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl]carbamate	IC50	1.43 nM	US-8841453: Hybrid cholinesterase inhibitors
prop-2-en-1-ylbis[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]amine	KI	1.6 nM
territrem B	KI	1.7 nM
3-{[methyl(7-{[(2E)-1-oxo-2-(3,4,5-trimethoxybenzylidene)-2,3-dihydro-1H-inden-5-yl]oxy}heptyl)amino]methyl}phenyl methylcarbamate	IC50	1.8 nM
CHEMBL4748114	IC50	1.9 nM
N-[8-(1,2,3,4-tetrahydroacridin-9-ylamino)octyl]-1,2,3,4-tetrahydroacridin-9-amine	KI	1.9 nM
3-{[methyl(7-{[(2Z)-3-oxo-2-(phenylmethylidene)-2,3-dihydro-1-benzofuran-6-yl]oxy}heptyl)amino]methyl}phenyl N-methylcarbamate	IC50	1.95 nM
CHEMBL4469343	IC50	2 nM
3-{[methyl(7-{[(2Z)-2-(2-naphthylmethylene)-3-oxo-2,3-dihydro-1-benzofuran-6-yl]oxy}heptyl)amino]methyl}phenyl methylcarbamate	IC50	2.09 nM
4-amino-5-chloro-[[1-(cyclohexylmethyl)-4-piperidyl]methyl]-2-methoxybenzamide	KI	2.3 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
1-(4-amino-5-chloro-2-methoxyphenyl)-3-[1-[(piperidin-4-yl)methyl]-4-piperidyl] propan-1-one	KI	2.5 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
1-[4-amino-5-chloro-2-(2-fluoroéthoxy)phenyl]-3-[1-(cyclohexylmethyl)-4-piperidyl]propan-1-one	KI	2.5 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
3-{[methyl(7-{[(2Z)-2-(1-naphthylmethylene)-3-oxo-2,3-dihydro-1-benzofuran-6-yl]oxy}heptyl)amino]methyl}phenyl methylcarbamate	IC50	2.76 nM
(4-Bromo-2,5-dihydroxyphenyl)(4-hydroxyphenyl)methanone (22)	KI	2.78 nM
Compound 12.HCl	IC50	2.8 nM
ethylbis[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]amine	KI	2.8 nM
CHEMBL4782921	IC50	2.9 nM
3-{[methyl(3-{[(2Z)-3-oxo-2-(3,4,5-trimethoxybenzylidene)-2,3-dihydro-1-benzofuran-6-yl]oxy}propyl)amino]methyl}phenyl methylcarbamate	IC50	2.99 nM
1-(4-amino-5-chloro-2-methoxyphenyl)-3-[1-(cyclopentylmethyl)piperidin-4-yl]propan-1-one	KI	3 nM	US-9663465: Acetylcholinesterase inhibitors and promnesiant serotonin 5-HT4 receptor agonists, their methods of preparation and the pharmaceutical compositions containing the same
(4-Bromo-2,5-dihydroxyphenyl)(phenyl)methanone (23)	KI	3.24 nM

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.98	Ki	0.0105	nM	CHEMBL3585779
10.96	IC50	0.01095	nM	CHEMBL4205425
10.93	Ki	0.0118	nM	CHEMBL489454
10.92	Ki	0.012	nM	CHEMBL489454
10.88	IC50	0.01323	nM	CHEMBL4205954
10.87	IC50	0.01352	nM	CHEMBL4209803
10.85	Ki	0.014	nM	CHEMBL225567
10.85	IC50	0.01415	nM	CHEMBL4217663
10.84	IC50	0.01441	nM	CHEMBL4210316
10.82	Ki	0.015	nM	CHEMBL223443
10.78	IC50	0.01672	nM	CHEMBL4214430
10.72	IC50	0.01893	nM	CHEMBL4213253
10.70	IC50	0.02	nM	CHEMBL225198
10.70	Ki	0.02	nM	CHEMBL225326
10.70	IC50	0.02	nM	CHEMBL225567
10.70	IC50	0.02	nM	CHEMBL1083983
10.68	IC50	0.02094	nM	CHEMBL4214707
10.67	IC50	0.02158	nM	CHEMBL4210041
10.66	Ki	0.022	nM	CHEMBL5433692
10.64	Ki	0.0229	nM	CHEMBL3585778
10.59	Ki	0.026	nM	HUPRINE X
10.59	IC50	0.02592	nM	CHEMBL4205144
10.58	IC50	0.02621	nM	CHEMBL4218191
10.57	IC50	0.02685	nM	CHEMBL3585777
10.57	IC50	0.02685	nM	CHEMBL3585776
10.57	IC50	0.02685	nM	CHEMBL3585775
10.57	IC50	0.02685	nM	CHEMBL3585778
10.57	IC50	0.02685	nM	CHEMBL3585779
10.57	IC50	0.02685	nM	CHEMBL3585780
10.57	IC50	0.02685	nM	CHEMBL3585781
10.57	IC50	0.02685	nM	CHEMBL3585782
10.57	IC50	0.02685	nM	CHEMBL3585783
10.57	IC50	0.02685	nM	CHEMBL3585784
10.55	IC50	0.02836	nM	CHEMBL4208866
10.53	IC50	0.02938	nM	CHEMBL4209518
10.48	Ki	0.033	nM	CHEMBL536047
10.46	IC50	0.035	nM	CHEMBL2019048
10.42	Ki	0.0382	nM	CHEMBL3585780
10.40	IC50	0.04	nM	CHEMBL372202
10.37	IC50	0.043	nM	NEOSTIGMINE BROMIDE
10.33	Ki	0.047	nM	CHEMBL3137700
10.22	IC50	0.06	nM	CHEMBL225198
10.22	IC50	0.06	nM	CHEMBL1083984
10.19	IC50	0.065	nM	CHEMBL2019049
10.17	IC50	0.068	nM	CHEMBL5190569
10.15	IC50	0.07	nM	CHEMBL225567
10.15	IC50	0.07	nM	CHEMBL307004
10.10	Ki	0.08	nM	CHEMBL3621322
10.07	Ki	0.0847	nM	CHEMBL507174
10.05	IC50	0.09	nM	CHEMBL2019053

PubChem BioAssay actives

1977 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
N-[7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]heptyl]-3-(1H-indol-3-yl)propanamide	282827: Inhibition of human brain AchE	ic50	<0.0001	uM
N-[6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]hexyl]-3-(1H-indol-3-yl)propanamide	282827: Inhibition of human brain AchE	ki	<0.0001	uM
1-methoxy-2-[1-(sulfamoylamino)ethyl]benzene	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
1,2-dimethoxy-4-[1-(sulfamoylamino)ethyl]benzene	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
1-methoxy-4-[1-(sulfamoylamino)ethyl]benzene	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
N-[7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]heptyl]-2-(1H-indol-3-yl)acetamide	282827: Inhibition of human brain AchE	ki	<0.0001	uM
N-[2-[5-[6-[(1R)-6,7-dimethoxy-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl]hexyl]triazol-1-yl]ethyl]-1,2,3,4-tetrahydroacridin-9-amine	1178308: Binding affinity to acetylcholine esterase (unknown origin)	kd	<0.0001	uM
N-[2-[5-[6-[(1S)-6,7-dimethoxy-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl]hexyl]triazol-1-yl]ethyl]-1,2,3,4-tetrahydroacridin-9-amine	1178308: Binding affinity to acetylcholine esterase (unknown origin)	kd	<0.0001	uM
N-[5-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]pentyl]-4-(1H-indol-3-yl)butanamide	282827: Inhibition of human brain AchE	ki	<0.0001	uM
2-(5-bromo-1H-indol-3-yl)-N-[7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]heptyl]acetamide	282827: Inhibition of human brain AchE	ki	<0.0001	uM
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
6-[(8-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
6-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(1H-indol-3-yl)ethyl]hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(1H-indol-3-yl)ethyl]hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
7-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]heptanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
N-[2-(1H-indol-3-yl)ethyl]-6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(1H-indol-3-yl)ethyl]heptanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
N-[2-(1H-indol-3-yl)ethyl]-7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
7-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(1H-indol-3-yl)ethyl]heptanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
5-(4-chlorophenyl)-N-[3-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]propyl]-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-9-carboxamide;hydrochloride	1183274: Inhibition of human recombinant AChE using acetylthiocholine iodide as substrate by spectrophotometric analysis	ic50	<0.0001	uM
benzyl N-[1-(2-methoxyphenyl)ethylsulfamoyl]carbamate	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
benzyl N-[1-(4-methoxyphenyl)ethylsulfamoyl]carbamate	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
benzyl N-[1-(3,4-dimethoxyphenyl)ethylsulfamoyl]carbamate	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
benzyl N-[1-(2,5-dimethoxyphenyl)ethylsulfamoyl]carbamate	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
benzyl N-[1-(2,6-dimethoxyphenyl)ethylsulfamoyl]carbamate	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
1,3-dimethoxy-2-[1-(sulfamoylamino)ethyl]benzene	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
6-[(2-methoxyphenyl)methyl-methylamino]-N-[8-[6-[(2-methoxyphenyl)methyl-methylamino]hexanoyl-methylamino]octyl]-N-methylhexanamide	31618: Inhibition constant determined against Acetylcholinesterase (AChE) receptor.	ki	0.0001	uM
N’-methyl-N-(1,2,3,4-tetrahydroacridin-9-yl)-N’-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]propane-1,3-diamine	1796269: Measurement of FBSAChE/EqBuChE Inhibitory Activity from Article 10.1021/jm049510k: “Development of molecular probes for the identification of extra interaction sites in the mid-gorge and peripheral sites of butyrylcholinesterase (BuChE). Rational design of novel, selective, and highly potent BuChE inhibitors.”	ki	0.0001	uM
N-[3-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]propyl]-5-[(3R)-dithiolan-3-yl]pentanamide	625546: Inhibition of human serum recombinant AChE after 20 mins using acetylthiocholine iodide as a substrate by Ellman’s assay	ic50	0.0002	uM
7-chloro-15-methyl-10-azatetracyclo[11.3.1.02,11.04,9]heptadeca-2,4(9),5,7,10,14-hexaen-3-amine	1545298: Inhibition of human Acetylcholinesterase using acetylthiocholine as substrate incubated for 15 mins by Ellman’s method	ic50	0.0003	uM
[3-[[methyl-[3-(9-oxoxanthen-3-yl)oxypropyl]amino]methyl]phenyl] N-methylcarbamate	1796503: Cholinesterase Inhibition Assay from Article 10.1021/jm049515h: “Cholinesterase inhibitors: xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation.”	ic50	0.0003	uM
[3-[[methyl-[7-(9-oxoxanthen-3-yl)oxyheptyl]amino]methyl]phenyl] N-methylcarbamate	1796503: Cholinesterase Inhibition Assay from Article 10.1021/jm049515h: “Cholinesterase inhibitors: xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation.”	ic50	0.0003	uM
N-[3-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]propyl]-5-(dithiolan-3-yl)pentanamide	1127774: Inhibition of AChE (unknown origin)	ic50	0.0003	uM
2-methyl-5-[9-(2-methylpyrido[4,3-b]indol-2-ium-5-yl)nonyl]pyrido[4,3-b]indol-2-ium diiodide	1766053: Inhibition of recombinant human AChE expressed in HEK293 cells by Ellman’s method	ic50	0.0003	uM
3-[2-(1-benzylpiperidin-4-yl)ethyl]-5,7-dihydropyrrolo[3,2-f][1,2]benzoxazol-6-one;(Z)-but-2-enedioic acid	31169: In vitro inhibition of Acetylcholinesterase from human erythrocytes	ic50	0.0003	uM
2-[(1-benzyl-3-bromopyridin-1-ium-4-yl)methyl]-5,6-dimethoxy-2,3-dihydroinden-1-one bromide	1351939: Inhibition of human erythrocyte AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured every minute for 10 mins by Ellman’s method	ic50	0.0004	uM
2-(dimethylsulfamoylamino)-5-methoxy-1,2,3,4-tetrahydronaphthalene	1292255: Inhibition of AChE (unknown origin) using acetylcholine iodate as substrate preincubated for 10 mins followed by substrate addition by Lineweaver-Burk plot analysis	ki	0.0004	uM
3-[2-(1-benzylpiperidin-4-yl)ethyl]-7-methyl-5H-pyrrolo[3,2-f][1,2]benzoxazol-6-one	566585: Inhibition of human acetylcholinesterase	ic50	0.0005	uM
N-[8-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]octyl]-3-(1H-indol-3-yl)propanamide	482894: Inhibition of AChE	ic50	0.0005	uM
N-[6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]hexyl]-4-(1H-indol-3-yl)butanamide	482894: Inhibition of AChE	ic50	0.0005	uM
[3-[[methyl-[7-[[(2Z)-3-oxo-2-[(3,4,5-trimethoxyphenyl)methylidene]-1-benzofuran-6-yl]oxy]heptyl]amino]methyl]phenyl] N-methylcarbamate	1796503: Cholinesterase Inhibition Assay from Article 10.1021/jm049515h: “Cholinesterase inhibitors: xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation.”	ic50	0.0005	uM
3-[2-(1-benzylpiperidin-4-yl)ethyl]-7,8-dihydro-5H-[1,2]oxazolo[4,5-g]quinolin-6-one	482894: Inhibition of AChE	ic50	0.0005	uM
[3-[[ethyl-[3-(9-oxoxanthen-3-yl)oxypropyl]amino]methyl]phenyl] N-methylcarbamate	1796566: Cholinesterase Inhibition Assay from Article 10.1021/jm9810046: “Acetylcholinesterase inhibitors: synthesis and structure-activity relationships of omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl derivatives.”	ic50	0.0006	uM
2-[bis[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]amino]ethanol	1796269: Measurement of FBSAChE/EqBuChE Inhibitory Activity from Article 10.1021/jm049510k: “Development of molecular probes for the identification of extra interaction sites in the mid-gorge and peripheral sites of butyrylcholinesterase (BuChE). Rational design of novel, selective, and highly potent BuChE inhibitors.”	ki	0.0006	uM
3-[2-(1-benzylpiperidin-4-yl)ethyl]-6,8-dihydro-5H-[1,2]oxazolo[4,5-g]quinolin-7-one	239914: Binding affinity towards Acetylcholinesterase	ki	0.0006	uM
[3-[[3-(9-oxoxanthen-3-yl)oxypropyl-propan-2-ylamino]methyl]phenyl] N-methylcarbamate	1796566: Cholinesterase Inhibition Assay from Article 10.1021/jm9810046: “Acetylcholinesterase inhibitors: synthesis and structure-activity relationships of omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl derivatives.”	ic50	0.0007	uM
N-[6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]hexyl]-3-(5-cyano-1H-indol-3-yl)propanamide	482894: Inhibition of AChE	ic50	0.0007	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Paraoxon	decreases activity, affects cotreatment, affects reaction, increases expression, increases phosphorylation (+4 more)	39
Sarin	affects reaction, increases reaction, decreases expression, increases metabolic processing, increases phosphorylation (+5 more)	37
pralidoxime	decreases activity, affects binding, decreases reaction, increases reaction, affects reaction	36
asoxime chloride	increases reaction, affects reaction, decreases activity, decreases reaction, increases activity (+3 more)	35
Obidoxime Chloride	increases activity, affects cotreatment, affects reaction, decreases activity, decreases reaction (+1 more)	34
tabun	decreases reaction, affects binding, affects cotreatment, affects reaction, increases phosphorylation (+1 more)	31
VX-agent	increases metabolic processing, decreases activity, decreases reaction, decreases response to substance, increases reaction (+2 more)	30
methamidophos	decreases activity, decreases reaction, affects binding, increases phosphorylation, affects cotreatment (+1 more)	20
cyclohexyl methylphosphonofluoridate	affects reaction, affects binding, increases metabolic processing, affects cotreatment, decreases activity (+1 more)	19
Dichlorvos	decreases activity, decreases reaction, affects cotreatment, increases reaction, increases phosphorylation (+1 more)	19
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects reaction, decreases activity, affects binding, increases phosphorylation, decreases reaction	16
Soman	increases response to substance, affects binding, decreases activity, decreases reaction, decreases carbamoylation (+1 more)	15
N,N’-monomethylenebis(pyridiniumaldoxime)	decreases reaction, affects reaction, decreases activity, affects binding	14
Trichlorfon	affects cotreatment, decreases activity, decreases reaction	14
Chlorpyrifos	decreases activity, decreases reaction, affects cotreatment, increases expression, affects reaction	13
Organophosphorus Compounds	decreases response to substance, increases metabolic processing, decreases activity, decreases reaction, increases abundance	11
malaoxon	decreases activity, decreases reaction, affects cotreatment	9
Diazinon	affects cotreatment, decreases activity, increases abundance, decreases reaction	9
Pesticides	decreases abundance, increases abundance, affects response to substance, decreases activity, decreases expression	9
mipafox	affects binding, decreases activity, decreases reaction	8
Isoflurophate	decreases activity, decreases reaction	8
Oximes	decreases activity, decreases reaction, affects binding	8
Tacrine	affects reaction, decreases activity	8
Acetylthiocholine	decreases reaction, increases hydrolysis, increases metabolic processing, affects binding	7
2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide	decreases activity, increases reaction, affects binding	6
HLo 7	affects reaction, decreases activity, decreases reaction	6
S-(N,N-diethylaminoethyl) isobutyl methylphosphothiolate	affects reaction, decreases activity, decreases reaction	6
Donepezil	affects reaction, decreases activity, affects binding, decreases reaction, increases reaction	6
Aldicarb	decreases activity	6
Galantamine	increases reaction, affects binding, decreases activity, decreases reaction	6

ChEMBL screening assays

2563 unique, capped per target: 2513 binding, 27 admet, 22 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004516	Binding	Selectivity ratio of IC50 for human serum BChE to IC50 for human serum AChE	Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimer’s disease. — J Med Chem
CHEMBL1648945	Functional	Antagonist activity at human nAChR in human SH-SY5Y cells assessed as inhibition of acetylcholine-induced cytosolic Ca2+ signal at 0.3 to 100 uM	Cholinergic and neuroprotective drugs for the treatment of Alzheimer and neuronal vascular diseases. II. Synthesis, biological assessment, and molecular modelling of new tacrine analogues from highly substituted 2-aminopyridine-3-carbonitriles. — Bioorg Med Chem
CHEMBL3283247	ADMET	Stability of the compound assessed as acetylcholinesterase (unknown origin)-mediated hydrolysis at 5 X 10’-3 M	Chemistry and biological activities of N,N-dimethylaminoethyl acrylate, a choline acetyltransferase inhibitor. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1IS	Abcam HeLa ACHE KO	Cancer cell line	Female
CVCL_SB21	HAP1 ACHE (-) 1	Cancer cell line	Male
CVCL_SB22	HAP1 ACHE (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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