BCHE

Summary

BCHE (butyrylcholinesterase, HGNC:983) is a protein-coding gene on chromosome 3q26.1, encoding Cholinesterase (P06276). Esterase with broad substrate specificity.

This gene encodes a cholinesterase enzyme and member of the type-B carboxylesterase/lipase family of proteins. The encoded enzyme exhibits broad substrate specificity and is involved in the detoxification of poisons including organophosphate nerve agents and pesticides, and the metabolism of drugs including cocaine, heroin and aspirin. Humans homozygous for certain mutations in this gene exhibit prolonged apnea after administration of the muscle relaxant succinylcholine.

Source: NCBI Gene 590 — RefSeq curated summary.

At a glance

• Gene–disease (curated): butyrylcholinesterase deficiency (Definitive, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 237 total — 14 pathogenic, 41 likely-pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes — 36 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_000055

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:983
Approved symbol	BCHE
Name	butyrylcholinesterase
Location	3q26.1
Locus type	gene with protein product
Status	Approved
Aliases	E1
Ensembl gene	ENSG00000114200
Ensembl biotype	protein_coding
OMIM	177400
Entrez	590

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 nonsense_mediated_decay

ENST00000264381, ENST00000479451, ENST00000482958, ENST00000488954, ENST00000497011, ENST00000855336, ENST00000855337, ENST00000855338, ENST00000855339

RefSeq mRNA: 1 — MANE Select: NM_000055 NM_000055

CCDS: CCDS3198

Canonical transcript exons

ENST00000264381 — 4 exons

Exon	Start	End
ENSE00000826111	165829517	165831041
ENSE00001810445	165772904	165773506
ENSE00001954521	165837314	165837423
ENSE00003548240	165786145	165786311

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 98.86.

FANTOM5 (CAGE): breadth broad, TPM avg 8.2962 / max 792.0520, expressed in 838 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45441	8.0160	833
45440	0.2802	122

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parietal pleura	UBERON:0002400	98.86	gold quality
adrenal tissue	UBERON:0018303	97.73	gold quality
right lobe of liver	UBERON:0001114	96.05	gold quality
germinal epithelium of ovary	UBERON:0001304	95.93	gold quality
liver	UBERON:0002107	94.92	gold quality
left uterine tube	UBERON:0001303	94.69	gold quality
pleura	UBERON:0000977	94.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.41	gold quality
lower esophagus	UBERON:0013473	92.34	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.98	gold quality
pericardium	UBERON:0002407	90.22	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.22	gold quality
seminal vesicle	UBERON:0000998	89.57	gold quality
visceral pleura	UBERON:0002401	88.18	gold quality
ventricular zone	UBERON:0003053	87.63	gold quality
omental fat pad	UBERON:0010414	86.91	gold quality
peritoneum	UBERON:0002358	86.89	gold quality
body of uterus	UBERON:0009853	85.83	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.67	gold quality
sigmoid colon	UBERON:0001159	84.79	gold quality
rectum	UBERON:0001052	84.72	gold quality
smooth muscle tissue	UBERON:0001135	84.46	gold quality
endocervix	UBERON:0000458	83.12	gold quality
amygdala	UBERON:0001876	82.87	gold quality
corpus epididymis	UBERON:0004359	82.07	gold quality
vena cava	UBERON:0004087	81.73	gold quality
ganglionic eminence	UBERON:0004023	81.31	gold quality
skin of hip	UBERON:0001554	81.14	gold quality
myometrium	UBERON:0001296	80.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.63	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-81608	yes	300.40
E-ENAD-27	yes	267.45
E-MTAB-5061	yes	192.98
E-MTAB-10553	yes	33.26
E-ANND-3	yes	10.62
E-GEOD-93593	yes	4.85
E-GEOD-81547	yes	4.73
E-GEOD-83139	no	3.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZNF354C

miRNA regulators (miRDB)

43 targeting BCHE, 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-5696	99.98	72.36	4487
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-3146	98.85	66.77	601
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-1183	98.75	67.10	1116

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Mutations associated with prolonged neuromuscular block during anesthesia. (PMID:11749053)
• Butyrylcholinesterase K variant on chromosome 3 q is associated with Type II diabetes in white Caucasian subjects. (PMID:11793025)
• can hydrolyze acetylcholine in the normal and Alzheimer brain. (PMID:11848688)
• Engineering of a monomeric and low-glycosylated form (PMID:11856322)
• Human butyrylcholinesterase is reversibly inhibited by tetraethylammonium ion. (PMID:11856351)
• serum enzyme inhibited by antidepressants, fluoxetine, sertraline and amitriptyline, in a dose related manner (PMID:12009429)
• BuChE-catalyzed hydrolysis of N-methylindoxyl acetate: analysis of volume changes upon reaction and hysteretic behavior. Hydrolysis by wild-type BuChE and peripheral site mutants (D70G, Y332A, D70G/Y332A) was found to follow Michaelis-Menten kinetics. (PMID:12044901)
• There is a minor association between BChE-K and early-onset coronary artery disease, especially in the presence of the APOE-epsilon 4 allele (PMID:12074828)
• Wild-type and A328W mutant expressed in Chinese hamster ovary cells have a 16-hour half-life in the circulation and protect mice from cocaine toxicity. (PMID:12130740)
• Novel mutation and multiple mutations found in the human butyrylcholinesterase gene affect enzyme activity. (PMID:12417112)
• Butyrylcholinesterase is a major regulator of attention especially in cholinergic deficiency states through its ability to hydrolyse acetylcholine. (PMID:12668920)
• Data help to better define the etiology of low BChE activity and the role of the rather common K allele (PMID:12724618)
• The distinct distribution of BuChE activity in neurons in the human thalamus is consistent with an important role for this enzyme in neurotransmission in the human nervous system. (PMID:12811800)
• the structure of BChE is similar to a previously published theoretical model of this enzyme and to the structure of Torpedo acetylcholinesterase (PMID:12869558)
• replacement of Ala277(Trp279) with Trp in human BChE does not affect the binding of E2020 to BChE (PMID:14622273)
• Theoretical analysis of the oscillatory behaviour of the approach to the steady-state for BuChE led us to propose a model for the hysteresis of BuChE with Benzoylcholine. (PMID:14686935)
• analysis of global dynamics of human butyrylcholinesterase in solvents (PMID:15111428)
• BCHE K polymorphism is associated with Type 2 diabetes or with estimates of pancreatic beta cell function in large-scale Danish Caucasian populations. (PMID:15258737)
• This study reports the first data on the relation of BCHE alleles to anthropometric characters. (PMID:15386241)
• Both bambuterol and terbutaline inhibit BChE, but their affinities differ in human serum BChE variants. (PMID:15449725)
• When genetically transferred into rats, accelerated cocaine metabolism. (PMID:15465921)
• BChE-K variant and ApoE-epsilon 4 alleles act synergistically to increase the risk of late-onset Alzheimer’s disease, particularly in age group <75 years in Tehran, Iran. (PMID:15519745)
• compareison of theoretical results with those from previous work on mouse acetylcholinesterase and discussion of their implications for substrate binding and catalysis in BuChE. (PMID:15696543)
• four new mutations, found in the exon 2 of the BCHE gene, in a sample from 3001 Brazilian blood donors.A table with the 58 non-usual variants of butyrylcholinesterase is also presented (PMID:15781196)
• BuChE may play role in the phosphorylation of tau in Alzheimer disease (PMID:15802910)
• The results suggest the involvement of BuChE in the pathophysiological process constituting the metabolic syndrome. (PMID:15907830)
• Human plasma contains four esterases: butyrylcholinesterase, paraoxonase, acetylcholinesterase, and albumin. (PMID:16213467)
• failure to observe increased [(11)C]BMP hydrolysis in vivo makes it less likely that incremental BuChE contributes importantly to acetylcholine hydrolysis in Alzheimer disease (PMID:16278840)
• Effects of the oxyanion hole on the energy barriers provide valuable clues on how to rationally design BChE mutants with a higher catalytic activity for the hydrolysis of cocaine. (PMID:16288482)
• pharmacokinetics of BuChE were evaluated in guinea pigs and in cynomolgus monkeys (PMID:16289064)
• K allele of butyrylcholinesterase in diabetes mellitus, Type 2 may predispose to a higher risk of metabolic syndrome (PMID:16429499)
• The hydrolysis of anilides and esters of choline appears to utilize the same catalytic site in BuChE. (PMID:16504521)
• In Alzheimer’s disease, BChE may have thus acquired an inverse role to that of AChE by adopting imperfect amphipathic characteristics of its C terminus (PMID:16731619)
• These findings suggest that the Polyethyleneglycol conjugated (PEGylated) recombinant human acetylcholinesterase exhibits unaltered biodistribution and high bioavailability. (PMID:16801396)
• Down-regulation of butyrylcholinesterase is associated with colorectal carcinoma (PMID:16909200)
• H(2)O(2) is a major player in the regulation of the cholinergic signal via both acetylcholinesterase and BchE and this signal is severely affected in the epidermis of patients with active vitiligo (PMID:16962996)
• We hypothesize that CSF BuChE varies inversely with BuChE in cortical amyloid plaques. Thus, low BuChE in a patient’s CSF may predict extensive incorporation in neuritic plaques, increased neurotoxicity and greater central neurodegeneration. (PMID:16973370)
• Levels are decreased in colonic adenocarcinomas. (PMID:17192624)
• the 1615G –> A polymorphism BCHE genotype was independently associated with in-stent restenosis in a Japanese population (PMID:17275003)
• Different profiles of cognitive test performance between individuals with silent and wild-type BuChE are observed and suggest a function for BuChE in cognition. (PMID:17318303)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Bche	ENSMUSG00000027792
rattus_norvegicus	Bche	ENSRNOG00000009826
drosophila_melanogaster	Ace	FBGN0000024
caenorhabditis_elegans	ace-2	WBGENE00000036

Paralogs (13): TG (ENSG00000042832), ACHE (ENSG00000087085), 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

Cholinesterase — P06276 (reviewed: P06276)

Alternative names: Acylcholine acylhydrolase, Butyrylcholine esterase, Choline esterase II, Pseudocholinesterase

All UniProt accessions (5): P06276, F8WEX7, F8WF14, H0Y885, H7C4Y0

UniProt curated annotations — full annotation on UniProt →

Function. Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.

Subunit / interactions. Homotetramer; disulfide-linked. Dimer of dimers.

Subcellular location. Secreted.

Tissue specificity. Detected in blood plasma (at protein level). Present in most cells except erythrocytes.

Post-translational modifications. N-glycosylated. No other PTM detected. The major N-glycan structures are of the complex diantennary type with 1 and 2 N-acetylneuraminic acid molecules (Neu5Ac) making up approximately 33% and 47% of the total N-glycans, respectively. Only low amounts of fucosylated diantennary N-glycans are detected (approximately 2%). Triantennary N-glycans with or without fucose amount to approximately 13%, whereas 5% of the total N-glycans are of the oligomannosidic or hybrid type.

Disease relevance. Butyrylcholinesterase deficiency (BCHED) [MIM:617936] An autosomal recessive metabolic condition characterized by increased sensitivity to certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium. BCHED results in slower hydrolysis of these drugs and, consequently, a prolonged neuromuscular block, leading to apnea. The duration of the prolonged apnea varies significantly depending on the extent of the enzyme deficiency. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by mercury. Inhibited by Tabun. Tabun forms a covalent adduct with Ser-226 that becomes irreversible upon aging.

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

RefSeq proteins (1): NP_000046* (*=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 3.1.1.8 — cholinesterase (BRENDA: 97 organisms, 292 substrates, 1528 inhibitors, 221 Km, 106 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
BUTYRYLTHIOCHOLINE	0.0001–6	47
ACETYLTHIOCHOLINE	0.019–4.8	30
PROPIONYLTHIOCHOLINE	0.006–5.4	26
BUTYRYLTHIOCHOLINE IODIDE	0.03–3.9	17
BUTANOYLTHIOCHOLINE	0.0051–0.34	11
BENZOYLCHOLINE	0.003–0.047	10
(-)-COCAINE	0.0031–0.065	6
BENZOYLTHIOCHOLINE	0.0029–0.135	6
ACETYLCHOLINE	0.027–0.148	5
2-NITROPHENYL BUTYRATE	0.12–1.9	4
ACETYLTHIOCHOLINE IODIDE	0.057–1.476	4
BUTYRYLCHOLINE	0.29–7.1	4
N-METHYLINDOXYL ACETATE	0.066–0.162	4
SUCCINYLTHIOCHOLINE	0.003–11	3
ACETYLCHOLINE IODIDE	0.08–0.14	2

Catalyzed reactions (Rhea), 1 shown:

• an acylcholine + H2O = a carboxylate + choline + H(+) (RHEA:21964)

UniProt features (122 total): sequence variant 44, helix 26, strand 21, glycosylation site 10, turn 8, disulfide bond 4, active site 3, binding site 3, signal peptide 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

109 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6ZWI	X-RAY DIFFRACTION	1.85
6QAA	X-RAY DIFFRACTION	1.9
1P0I	X-RAY DIFFRACTION	2
2WSL	X-RAY DIFFRACTION	2
7AWG	X-RAY DIFFRACTION	2
7QHD	X-RAY DIFFRACTION	2.04
1XLW	X-RAY DIFFRACTION	2.1
2WIJ	X-RAY DIFFRACTION	2.1
2WIK	X-RAY DIFFRACTION	2.1
2XMB	X-RAY DIFFRACTION	2.1
2XQF	X-RAY DIFFRACTION	2.1
3DJY	X-RAY DIFFRACTION	2.1
4BDS	X-RAY DIFFRACTION	2.1
5NN0	X-RAY DIFFRACTION	2.1
8QTX	X-RAY DIFFRACTION	2.12
7QBR	X-RAY DIFFRACTION	2.13
8AI7	X-RAY DIFFRACTION	2.13
2WIG	X-RAY DIFFRACTION	2.15
9R3B	X-RAY DIFFRACTION	2.15
9R9D	X-RAY DIFFRACTION	2.16
9R9E	X-RAY DIFFRACTION	2.18
1XLU	X-RAY DIFFRACTION	2.2
7BO3	X-RAY DIFFRACTION	2.2
8QTW	X-RAY DIFFRACTION	2.24
1XLV	X-RAY DIFFRACTION	2.25
2WIF	X-RAY DIFFRACTION	2.25
7AMZ	X-RAY DIFFRACTION	2.25
1P0P	X-RAY DIFFRACTION	2.3
2WID	X-RAY DIFFRACTION	2.3
2XMD	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06276-F1	93.30	0.83

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): 226 (acyl-ester intermediate); 353 (charge relay system); 466 (charge relay system)

Ligand- & substrate-binding residues (3): 110; 144–145; 466

Post-translational modifications (1): 226

Disulfide bonds (4): 93–120, 280–291, 428–547, 599

Glycosylation sites (10): 85, 134, 269, 284, 369, 483, 509, 513, 514, 45

Function

Pathways and Gene Ontology

Reactome pathways

4 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-9749641	Aspirin ADME

MSigDB gene sets: 188 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_COGNITION, GOBP_BEHAVIOR, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPONSE_TO_CORTICOSTEROID, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEUROGENESIS, MAHADEVAN_IMATINIB_RESISTANCE_DN, chr3q26, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_UP, GOBP_CELL_CELL_SIGNALING, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_PROTEIN_MATURATION, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN

GO Biological Process (15): acetylcholine catabolic process (GO:0006581), xenobiotic metabolic process (GO:0006805), learning (GO:0007612), negative regulation of cell population proliferation (GO:0008285), neuroblast differentiation (GO:0014016), peptide hormone processing (GO:0016486), choline metabolic process (GO:0019695), response to alkaloid (GO:0043279), cocaine catabolic process (GO:0050784), negative regulation of synaptic transmission (GO:0050805), response to glucocorticoid (GO:0051384), response to folic acid (GO:0051593), response to nutrient (GO:0007584), response to xenobiotic stimulus (GO:0009410), obsolete cocaine metabolic process (GO:0050783)

GO Molecular Function (11): amyloid-beta binding (GO:0001540), catalytic activity (GO:0003824), acetylcholinesterase activity (GO:0003990), cholinesterase activity (GO:0004104), hydrolase activity, acting on ester bonds (GO:0016788), enzyme binding (GO:0019899), choline binding (GO:0033265), identical protein binding (GO:0042802), protein binding (GO:0005515), hydrolase activity (GO:0016787), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nuclear envelope lumen (GO:0005641), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), blood microparticle (GO:0072562), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Transmission across Chemical Synapses	1
Glycerophospholipid biosynthesis	1
Peptide hormone metabolism	1
Drug ADME	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	2
response to nitrogen compound	2
response to chemical	2
protein binding	2
cellular anatomical structure	2
acetylcholine metabolic process	1
catabolic process	1
cellular response to xenobiotic stimulus	1
learning or memory	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell differentiation	1
generation of neurons	1
hormone metabolic process	1
signaling receptor ligand precursor processing	1
alkaloid catabolic process	1
chemical synaptic transmission	1
negative regulation of cell communication	1
negative regulation of signaling	1
modulation of chemical synaptic transmission	1
response to corticosteroid	1
response to vitamin	1
response to oxygen-containing compound	1
response to nutrient levels	1
peptide binding	1
molecular_function	1
cholinesterase activity	1
carboxylic ester hydrolase activity	1
hydrolase activity	1
cation binding	1
binding	1
catalytic activity	1
hydrolase activity, acting on ester bonds	1
nuclear envelope	1
organelle envelope lumen	1
endoplasmic reticulum	1
intracellular organelle lumen	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCHE	COLQ	Q9Y215	967
BCHE	ALB	P02768	903
BCHE	CHAT	P28329	871
BCHE	APOE	P02649	829
BCHE	GPT	P24298	828
BCHE	DOK7	Q18PE1	798
BCHE	MAOB	P27338	791
BCHE	PON1	P27169	788
BCHE	MGAM	O43451	771
BCHE	SI	P14410	771
BCHE	MAOA	P21397	745
BCHE	MUSK	O15146	743
BCHE	BACE1	P56817	742
BCHE	CRP	P02741	731
BCHE	APP	P05067	721

IntAct

91 interactions, top by confidence:

A	B	Type	Score
BCHE	BCHE	psi-mi:“MI:0407”(direct interaction)	0.840
BCHE	ENTPD5	psi-mi:“MI:0914”(association)	0.640
SMR3B	BCHE	psi-mi:“MI:0915”(physical association)	0.560
BCHE	SEC11A	psi-mi:“MI:0915”(physical association)	0.560
CASP6	BCHE	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	BCHE	psi-mi:“MI:0915”(physical association)	0.560
RAN	BCHE	psi-mi:“MI:0915”(physical association)	0.560
BAG6	BCHE	psi-mi:“MI:0915”(physical association)	0.560
KLF11	BCHE	psi-mi:“MI:0915”(physical association)	0.560
DNAJB6	BCHE	psi-mi:“MI:0915”(physical association)	0.560
PRPF40A	BCHE	psi-mi:“MI:0915”(physical association)	0.560
BCHE	ATXN3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (93): BCHE (Affinity Capture-MS), BCHE (Affinity Capture-MS), LOXL1 (Affinity Capture-MS), ENTPD5 (Affinity Capture-MS), LTBP1 (Affinity Capture-MS), NAF1 (Affinity Capture-MS), ACTN3 (Affinity Capture-MS), PALLD (Affinity Capture-MS), KIAA1598 (Affinity Capture-MS), BCHE (Affinity Capture-MS), BCHE (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), DKC1 (Affinity Capture-MS), MANEAL (Affinity Capture-MS), BCHE (Affinity Capture-MS)

ESM2 similar proteins: A0A8B0RBM2, B2D0J5, D6WMZ8, O16168, O16169, O16170, O16171, O16172, O16173, O42275, O62760, O62761, P04058, P06276, P07692, P08171, P12992, P16303, P18167, P21927, P25725, P25726, P25727, P30122, P32749, P35501, P35502, P38433, P47982, P81908, Q03311, Q04456, Q04457, Q04791, Q05487, Q08662, Q27459, Q27677, Q5GRG2, Q63010

Diamond homologs: A0A060S684, A0A0E4AET8, A0A8B0RBM2, B0F2B4, D2D3B6, D6WMZ8, G3V7J5, I1RDA9, O00748, O16168, O16169, O16170, O16171, O16172, O16173, O42275, O46421, O62760, O62761, O70631, P04058, P06276, P07882, P08171, P0C6R3, P10959, P12337, P12992, P14943, P16303, P16854, P18142, P19835, P21837, P21927, P23141, P23953, P25725, P25726, P25727

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
HIPK2	“down-regulates quantity”	BCHE	phosphorylation
BCHE	“down-regulates quantity”	acetylcholine	“chemical modification”
Pyridostigmine	“down-regulates activity”	BCHE	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	41
Uncertain significance	132
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
13216	NM_000055.4(BCHE):c.435delinsAG (p.Phe146fs)	Pathogenic
13222	BCHE Newfoundland	Pathogenic
13223	BCHE Cynthiana	Pathogenic
13224	BCHE Johannesburg	Pathogenic
13225	NM_000055.4:c.1160_1161ins[N[342];1146_1160]	Pathogenic
13227	NM_000055.4(BCHE):c.467A>G (p.Tyr156Cys)	Pathogenic
13229	BCHE*FS126	Pathogenic
1324374	NM_000055.4(BCHE):c.1129G>T (p.Glu377Ter)	Pathogenic
225301	NM_000055.4(BCHE):c.1177G>C (p.Gly393Arg)	Pathogenic
2682418	NM_000055.4(BCHE):c.777G>A (p.Trp259Ter)	Pathogenic
3024629	GRCh37/hg19 3q26.1-26.2(chr3:164432414-167873834)x1	Pathogenic
344097	NM_000055.4(BCHE):c.428G>A (p.Gly143Asp)	Pathogenic
552544	NM_000055.4(BCHE):c.382C>T (p.Pro128Ser)	Pathogenic
594478	NM_000055.4(BCHE):c.100del (p.Ile34fs)	Pathogenic
13217	NM_000055.4(BCHE):c.508G>A (p.Val170Met)	Likely pathogenic
1323972	NM_000055.4(BCHE):c.1158del (p.Pro387fs)	Likely pathogenic
1323974	NM_000055.4(BCHE):c.824_827dup (p.Lys276delinsAsnTer)	Likely pathogenic
1677196	NM_000055.4(BCHE):c.594T>G (p.Asp198Glu)	Likely pathogenic
2437005	NM_000055.4(BCHE):c.932_935dup (p.Pro313fs)	Likely pathogenic
2501206	NM_000055.4(BCHE):c.1171_1174dup (p.Phe392Ter)	Likely pathogenic
370179	NM_000055.4(BCHE):c.666_667del (p.Phe223fs)	Likely pathogenic
370346	NM_000055.4(BCHE):c.895G>T (p.Glu299Ter)	Likely pathogenic
370364	NM_000055.4(BCHE):c.793del (p.Tyr265fs)	Likely pathogenic
370388	NM_000055.4(BCHE):c.1073dup (p.Leu358fs)	Likely pathogenic
370431	NM_000055.4(BCHE):c.1528G>T (p.Glu510Ter)	Likely pathogenic
370446	NM_000055.4(BCHE):c.1684+1G>T	Likely pathogenic
370447	NM_000055.4(BCHE):c.1685-2A>G	Likely pathogenic
370518	NM_000055.4(BCHE):c.495_498del (p.Arg166fs)	Likely pathogenic
370709	NM_000055.4(BCHE):c.493del (p.Glu165fs)	Likely pathogenic
370809	NM_000055.4(BCHE):c.206_207del (p.Leu69fs)	Likely pathogenic

SpliceAI

890 predictions. Top by Δscore:

Variant	Effect	Δscore
3:165775907:T:TA	donor_gain	1.0000
3:165775914:T:A	donor_gain	1.0000
3:165773503:TTTC:T	acceptor_gain	0.9900
3:165773504:TTC:T	acceptor_gain	0.9900
3:165773505:TC:T	acceptor_gain	0.9900
3:165773506:CC:C	acceptor_gain	0.9900
3:165773507:C:CC	acceptor_gain	0.9900
3:165786141:ACAC:A	donor_loss	0.9900
3:165786142:CA:C	donor_loss	0.9900
3:165786143:AC:A	donor_loss	0.9900
3:165786144:C:CA	donor_loss	0.9900
3:165786309:TTC:T	acceptor_gain	0.9900
3:165786310:TC:T	acceptor_gain	0.9900
3:165786311:CC:C	acceptor_gain	0.9900
3:165786311:CCTA:C	acceptor_loss	0.9900
3:165786312:C:CC	acceptor_gain	0.9900
3:165786312:CT:C	acceptor_loss	0.9900
3:165786313:T:G	acceptor_loss	0.9900
3:165837307:AACTT:A	donor_loss	0.9900
3:165837308:ACTTA:A	donor_loss	0.9900
3:165837309:CTTA:C	donor_loss	0.9900
3:165837311:TA:T	donor_loss	0.9900
3:165837312:AC:A	donor_gain	0.9900
3:165837312:ACCC:A	donor_loss	0.9900
3:165837313:C:CT	donor_loss	0.9900
3:165837313:CC:C	donor_gain	0.9900
3:165837371:T:TA	donor_gain	0.9900
3:165773504:TTCCT:T	acceptor_loss	0.9800
3:165773505:TCCT:T	acceptor_loss	0.9800
3:165773506:CCTG:C	acceptor_loss	0.9800

AlphaMissense

3999 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:165830510:C:A	R175M	0.987
3:165829653:A:G	W461R	0.985
3:165829653:A:T	W461R	0.985
3:165830509:C:A	R175S	0.984
3:165830509:C:G	R175S	0.984
3:165830666:A:G	L123P	0.984
3:165829651:C:A	W461C	0.983
3:165829651:C:G	W461C	0.983
3:165830491:G:C	F181L	0.983
3:165830491:G:T	F181L	0.983
3:165830493:A:G	F181L	0.983
3:165829539:A:G	W499R	0.982
3:165829539:A:T	W499R	0.982
3:165830278:A:C	S252R	0.980
3:165830278:A:T	S252R	0.980
3:165830280:T:G	S252R	0.980
3:165830455:G:C	N193K	0.979
3:165830455:G:T	N193K	0.979
3:165830510:C:G	R175T	0.978
3:165830658:A:G	W126R	0.977
3:165830658:A:T	W126R	0.977
3:165830674:A:C	C120W	0.976
3:165830662:A:C	N124K	0.975
3:165830662:A:T	N124K	0.975
3:165829558:A:C	S492R	0.974
3:165829558:A:T	S492R	0.974
3:165829560:T:G	S492R	0.974
3:165830421:A:G	W205R	0.974
3:165830421:A:T	W205R	0.974
3:165830279:C:A	S252I	0.972

dbSNP variants (sampled 300 via entrez): RS1000059265 (3:165799076 A>G), RS1000097292 (3:165777472 G>A,T), RS1000195546 (3:165822254 G>C), RS1000196327 (3:165783519 G>T), RS1000211717 (3:165775706 C>T), RS1000280946 (3:165810358 A>G), RS1000281274 (3:165793491 T>G), RS1000368916 (3:165826605 T>C), RS1000397891 (3:165826874 G>A), RS1000424863 (3:165781697 C>T), RS1000425489 (3:165820448 G>C), RS1000429388 (3:165834662 T>C), RS1000587006 (3:165781937 A>G), RS1000610678 (3:165803190 C>T), RS1000634082 (3:165814343 T>C)

Disease associations

OMIM: gene MIM:177400 | disease phenotypes: MIM:617936

GenCC curated gene-disease

Disease	Classification	Inheritance
butyrylcholinesterase deficiency	Definitive	Unknown

Mondo (1): butyrylcholinesterase deficiency (MONDO:0015270)

Orphanet (1): Hereditary butyrylcholinesterase deficiency (Orphanet:132)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001392	Abnormality of the liver
HP:0001635	Congestive heart failure
HP:0001658	Myocardial infarction
HP:0002104	Apnea
HP:0002664	Neoplasm
HP:0002878	Respiratory failure
HP:0003470	Paralysis
HP:0004887	Respiratory failure requiring assisted ventilation
HP:0012379	Abnormal circulating enzyme concentration or activity
HP:0031035	Chronic infection

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000675_16	Heart failure	6.000000e-06
GCST001207_3	Butyrylcholinesterase levels	6.000000e-262
GCST001247_5	Cardiovascular disease risk factors	6.000000e-92
GCST001868_10	Alzheimer’s disease biomarkers	3.000000e-08
GCST001910_1	Aspirin hydrolysis (plasma)	9.000000e-17
GCST004048_1	Fast beta electroencephalogram	5.000000e-09
GCST005352_10	Paclitaxel disposition in epithelial ovarian cancer	6.000000e-07
GCST005352_6	Paclitaxel disposition in epithelial ovarian cancer	5.000000e-07
GCST007430_27	Peak expiratory flow	5.000000e-08
GCST007431_40	Lung function (FEV1/FVC)	9.000000e-12
GCST007432_19	FEV1	6.000000e-07

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004571	butyrylcholinesterase measurement
EFO:0005194	amyloid-beta measurement
EFO:0005211	aspirin hydrolysis measurement
EFO:0004357	electroencephalogram measurement
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537417	Butyrylcholinesterase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1914 (SINGLE PROTEIN), CHEMBL2095233 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

36 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 894,876 (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
CHEMBL1115	PYRIDOSTIGMINE	4	13,658
CHEMBL1200970	ETHOPROPAZINE HYDROCHLORIDE	4	876
CHEMBL1201092	RIVASTIGMINE TARTRATE	4	13
CHEMBL1206	ETHOPROPAZINE	4	15,984
CHEMBL1294	QUINIDINE	4	71,943
CHEMBL1677	TACRINE HYDROCHLORIDE	4	11,745
CHEMBL1678	DONEPEZIL HYDROCHLORIDE	4	22,635
CHEMBL211471	NEOSTIGMINE METHYLSULFATE	4	2,191
CHEMBL278020	NEOSTIGMINE	4	9,463
CHEMBL295124	BERBERINE	4	26,682
CHEMBL338975	PHYSOSTIGMINE SALICYLATE	4	2,644
CHEMBL502	DONEPEZIL	4	43,493
CHEMBL636	RIVASTIGMINE	4	30,156
CHEMBL659	GALANTAMINE	4	30,894
CHEMBL772	RESERPINE	4	330,645
CHEMBL812	PYRIDOSTIGMINE BROMIDE	4	2,900
CHEMBL887	RASAGILINE	4	12,978
CHEMBL94	PHYSOSTIGMINE	4	14,305
CHEMBL95	TACRINE	4	35,360
CHEMBL310671	SACCHARIN	3	216,311
CHEMBL50	QUERCETIN	3
CHEMBL51085	EBSELEN	3
CHEMBL521589	BAMBUTEROL	3
CHEMBL589390	LATREPIRDINE	3
CHEMBL121810	GANSTIGMINE	2
CHEMBL123248	ESERIDINE	2
CHEMBL284237	DIZOCILPINE	2
CHEMBL31574	FISETIN	2
CHEMBL329012	ICOPEZIL MALEATE	2
CHEMBL395280	HUPERZINE A	2

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

PharmGKB clinical annotations

14 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1560022535	Toxicity	3	succinylcholine	Apnea
rs1799807	Toxicity	3	succinylcholine	Butyrylcholinesterase deficiency
rs1803274	Efficacy	3	rivastigmine	Alzheimer Disease;Lewy Body Disease
rs1803274	Other	3	cocaine	Cocaine dependence
rs1803274	Efficacy	3	donepezil	Alzheimer Disease;Cognitive disorder
rs1803274	Toxicity	3	succinylcholine	Butyrylcholinesterase deficiency
rs201820739	Toxicity	3	succinylcholine	Apnea
rs28933389	Toxicity	3	succinylcholine
rs28933390	Toxicity	3	succinylcholine
rs531738678	Toxicity	3	succinylcholine	Apnea
rs568724445	Toxicity	3	succinylcholine	Apnea
rs745364489	Toxicity	3	succinylcholine	Apnea
rs764841347	Toxicity	3	succinylcholine	Apnea
rs774072493	Toxicity	3	succinylcholine	Apnea

PharmGKB variants

17 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1355534	BCHE		0.00	0
rs1799807	BCHE	3	3.00	1	succinylcholine
rs1803274	BCHE	3	6.50	4	donepezil;succinylcholine;rivastigmine;cocaine
rs4263329	BCHE		0.00	0
rs4680662	BCHE		0.00	0
rs28933389	BCHE	3	0.00	1	succinylcholine
rs28933390	BCHE	3	0.25	1	succinylcholine
rs104893684	BCHE		0.00	0
rs772583466	BCHE		0.00	0
rs755648929	BCHE		0.00	0
rs764841347	BCHE	3	0.25	1	succinylcholine
rs568724445	BCHE	3	0.25	1	succinylcholine
rs1560022535	BCHE	3	0.25	1	succinylcholine
rs745364489	BCHE	3	0.50	1	succinylcholine
rs531738678	BCHE	3	0.25	1	succinylcholine
rs201820739	BCHE	3	0.25	1	succinylcholine
rs774072493	BCHE	3	0.25	1	succinylcholine

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Acetylcholine turnover

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
bambuterol	Inhibition	8.5	pIC50
physostigmine	Inhibition	7.8	pIC50
rivastigmine	Inhibition	7.4	pIC50
tacrine	Inhibition	7.2	pKi
pyridostigmine	Inhibition	6.05	pIC50

Binding affinities (BindingDB)

246 measured of 451 human assays (633 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
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
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
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
[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
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
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
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
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
Compound 12.HCl	IC50	2.8 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
3-{[methyl(3-{[(2Z)-2-(naphthalen-2-ylmethylidene)-3-oxo-2,3-dihydro-1-benzofuran-6-yl]oxy}propyl)amino]methyl}phenyl N-methylcarbamate	IC50	3.41 nM
[3-(2-acetamidoethyl)-1H-indol-5-yl] N-[12-(1,2,3,4-tetrahydroacridin-9-ylamino)dodecyl]carbamate	IC50	3.8 nM	US-8841453: Hybrid cholinesterase inhibitors
[3-(2-acetamidoethyl)-1H-indol-5-yl] N-[8-(1,2,3,4-tetrahydroacridin-9-ylamino)octyl]carbamate	IC50	4.61 nM	US-8841453: Hybrid cholinesterase inhibitors
3-{[methyl(7-{[(6E)-5-oxo-6-(3,4,5-trimethoxybenzylidene)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}heptyl)amino]methyl}phenyl methylcarbamate	IC50	4.94 nM
3-({3-(4-benzoylphenoxy)propylamino}methyl)phenyl N-methylcarbamate	IC50	5.4 nM
3-{[methyl({3-[(2-oxo-2H-chromen-7-yl)oxy]propyl})amino]methyl}phenyl N-methylcarbamate hydrochloride	IC50	5.7 nM
3-{[methyl({3-[(4-oxo-2-phenyl-4H-chromen-7-yl)oxy]propyl})amino]methyl}phenyl N-methylcarbamate hydrochloride	IC50	5.7 nM
(9E)-7-(7-(1,2,3,4-Tetrahydroacridin-9-ylamino)heptylamino)-9-ethylidene-3-methylbicyclo[3.3.1]non-3-ene-1-carboxylic Acid Methyl Ester	KI	6.4 nM
3-{[methyl({8-[(9-oxo-9H-xanthen-3-yl)oxy]octyl})amino]methyl}phenyl N-methylcarbamate	IC50	6.8 nM
3-{[methyl(3-{[(2Z)-2-(1-naphthylmethylene)-3-oxo-2,3-dihydro-1-benzofuran-6-yl]oxy}propyl)amino]methyl}phenyl methylcarbamate	IC50	6.86 nM
5-(1,2-dithiolan-3-yl)-N-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]pentanamide	IC50	6.96 nM
[3-(2-acetamidoethyl)-1H-indol-5-yl] N-[12-[(7-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]dodecyl]carbamate	IC50	7 nM	US-8841453: Hybrid cholinesterase inhibitors
[3-(2-acetamidoethyl)-1H-indol-5-yl] N-[7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]heptyl]carbamate	IC50	7.7 nM	US-8841453: Hybrid cholinesterase inhibitors
3-{[(7-{[(2Z)-2-[(3,4-dichlorophenyl)methylidene]-3-oxo-2,3-dihydro-1-benzofuran-6-yl]oxy}heptyl)(methyl)amino]methyl}phenyl N-methylcarbamate	IC50	8 nM
[3-(2-acetamidoethyl)-1H-indol-5-yl] N-[10-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]decyl]carbamate	IC50	8.1 nM	US-8841453: Hybrid cholinesterase inhibitors
(2S,6R)-3-methyl-8-thia-3-azatricyclo[7.4.0.0^{2,6}]trideca-1(13),9,11-trien-10-yl N-methylcarbamate hydrochloride	IC50	8.11 nM
3-({methyl[3-({5-oxo-5H-chromeno[2,3-b]pyridin-8-yl}oxy)propyl]amino}methyl)phenyl N-butylcarbamate hydrochloride	IC50	8.9 nM
3-{[methyl(7-{[(3E)-4-oxo-3-(3,4,5-trimethoxybenzylidene)-3,4-dihydro-2H-chromen-7-yl]oxy}heptyl)amino]methyl}phenyl methylcarbamate	IC50	9.81 nM
(3aS)-1,3a,8-trimethyl-1H,2H,3H,3aH,8H,8aH-pyrrolo[2,3-b]indol-5-yl N-(2-methylphenyl)carbamate	IC50	10 nM
tolserine.tartaric acid	IC50	10 nM
homotolserine	IC50	10 nM

ChEMBL bioactivities

3709 potent at pChembl≥5 of 4618 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.95	Ki	0.0111	nM	CHEMBL4080419
10.67	IC50	0.0212	nM	CHEMBL1814730
10.57	IC50	0.0267	nM	TACRINE
10.52	IC50	0.03	nM	CHEMBL224336
10.45	IC50	0.0352	nM	CHEMBL5080685
10.45	IC50	0.0354	nM	CHEMBL1814731
10.42	IC50	0.038	nM	CHEMBL2019034
10.41	IC50	0.039	nM	CHEMBL5201089
10.35	IC50	0.0449	nM	CHEMBL1814729
10.22	Ki	0.06	nM	CHEMBL3099496
10.19	Kd	0.064	nM	CHEMBL5201089
10.15	IC50	0.07	nM	CHEMBL4444855
10.10	IC50	0.08	nM	CHEMBL2019032
10.10	IC50	0.08	nM	CHEMBL5195228
10.03	Ki	0.094	nM	CHEMBL5201089
10.00	IC50	0.1	nM	CHEMBL2019038
10.00	IC50	0.1	nM	CHEMBL2019037
10.00	IC50	0.1	nM	CHEMBL2019035
10.00	IC50	0.1	nM	CHEMBL225198
9.96	IC50	0.11	nM	CHEMBL5200785
9.89	IC50	0.13	nM	CHEMBL5181960
9.88	Ki	0.131	nM	CHEMBL4089082
9.86	IC50	0.139	nM	CHEMBL219316
9.85	IC50	0.141	nM	CHEMBL219264
9.82	IC50	0.15	nM	CHEMBL2019030
9.82	IC50	0.15	nM	CHEMBL4476861
9.82	IC50	0.15	nM	CHEMBL570764
9.79	Ki	0.163	nM	CHEMBL32823
9.77	IC50	0.17	nM	CHEMBL4464964
9.75	IC50	0.177	nM	CHEMBL5092094
9.74	Ki	0.18	nM	CHEMBL5186889
9.66	IC50	0.22	nM	CHEMBL5184728
9.65	IC50	0.226	nM	CHEMBL384886
9.62	IC50	0.24	nM	CHEMBL3642053
9.60	IC50	0.25	nM	CHEMBL3642040
9.60	IC50	0.25	nM	CHEMBL3642049
9.60	IC50	0.25	nM	CHEMBL4293015
9.59	IC50	0.26	nM	CHEMBL4461027
9.59	IC50	0.26	nM	CHEMBL5201951
9.59	IC50	0.26	nM	CHEMBL5184944
9.58	IC50	0.265	nM	CHEMBL5078555
9.57	IC50	0.27	nM	CHEMBL3827288
9.57	Ki	0.27	nM	CHEMBL501587
9.55	IC50	0.28	nM	CHEMBL3642052
9.55	IC50	0.28	nM	CHEMBL3827610
9.53	IC50	0.293	nM	CHEMBL216159
9.49	IC50	0.32	nM	CHEMBL189957
9.49	IC50	0.32	nM	CHEMBL5282182
9.46	IC50	0.35	nM	CHEMBL5185039
9.43	Kd	0.37	nM	CHEMBL5195228

PubChem BioAssay actives

2849 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-(1H-indol-3-yl)-N-[3-[methyl-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]amino]propyl]propanamide	1796276: In Vitro Enzyme Inhibition Assay from Article 10.1021/jm0503289: “Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer’s disease.”	ic50	<0.0001	uM
N-[[1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl]methyl]-N-[2-(dimethylamino)ethyl]naphthalene-2-carboxamide;hydrochloride	1472409: Competitive inhibition of recombinant human BChE using butyrylthiocholine iodide as substrate at pH 8 by stopped flow assay	ki	<0.0001	uM
N-[5-(1,2,3,4-tetrahydroacridin-9-ylamino)pentyl]acridine-9-carboxamide	1529424: Inhibition of BuChE (unknown origin)	ic50	<0.0001	uM
methyl 2-methoxy-6-[8-(1,2,3,4-tetrahydroacridin-9-ylamino)octyl]benzoate	1831859: Inhibition of human serum BChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by Ellman’s method	ic50	<0.0001	uM
N-[[2-(diethylaminomethyl)phenyl]methyl]-3-[(4-fluorobenzoyl)amino]-5-methylbenzamide	1886723: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman’s method	ic50	<0.0001	uM
1,2,3,4-tetrahydroacridin-9-amine	612151: Inhibition of BChE by Ellman’s method	ic50	<0.0001	uM
N-[7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]heptyl]-3-(1H-indol-3-yl)propanamide	1796276: In Vitro Enzyme Inhibition Assay from Article 10.1021/jm0503289: “Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors: new disease-modifying agents for Alzheimer’s disease.”	ic50	0.0001	uM
naphthalen-1-yl-[3-(3-piperidin-1-ylpropoxy)indazol-1-yl]methanone	1601893: Inhibition of human serum BChE using butyrylthiocholine as substrate by Ellman’s assay	ic50	0.0001	uM
naphthalen-1-yl-[3-(3-pyrrolidin-1-ylpropoxy)indazol-1-yl]methanone	1601893: Inhibition of human serum BChE using butyrylthiocholine as substrate by Ellman’s assay	ic50	0.0001	uM
N-[[2-(diethylaminomethyl)phenyl]methyl]-3-[(4-iodobenzoyl)amino]benzamide	1886723: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman’s method	ic50	0.0001	uM
3-[(4-bromobenzoyl)amino]-N-[[2-(diethylaminomethyl)phenyl]methyl]benzamide	1886723: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman’s method	ic50	0.0001	uM
N-[6-oxo-6-[2-(1,2,3,4-tetrahydroacridin-9-yl)hydrazinyl]hexyl]-3-(3,4,5-trimethoxyphenyl)propanamide	1797052: Cholinesterase Inhibition Assay from Article 10.1021/jm060742o: “Novel heterobivalent tacrine derivatives as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase.”	ic50	0.0001	uM
N-[5-oxo-5-[2-(1,2,3,4-tetrahydroacridin-9-yl)hydrazinyl]pentyl]-3-(3,4,5-trimethoxyphenyl)propanamide	1797052: Cholinesterase Inhibition Assay from Article 10.1021/jm060742o: “Novel heterobivalent tacrine derivatives as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase.”	ic50	0.0001	uM
(2S)-2-acetamido-N-[(1-benzylpiperidin-4-yl)methyl]-3-(4-phenyltriazol-1-yl)propanamide	1625094: Inhibition of recombinant human BuChE using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured for 5 mins by Ellman’s method	ic50	0.0002	uM
N-[4-oxo-4-[2-(1,2,3,4-tetrahydroacridin-9-yl)hydrazinyl]butyl]-3-(3,4,5-trimethoxyphenyl)propanamide	1797052: Cholinesterase Inhibition Assay from Article 10.1021/jm060742o: “Novel heterobivalent tacrine derivatives as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase.”	ic50	0.0002	uM
methyl 2-hydroxy-6-[8-(1,2,3,4-tetrahydroacridin-9-ylamino)octyl]benzoate	1831859: Inhibition of human serum BChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by Ellman’s method	ic50	0.0002	uM
[3-[2-[butyl(2-cycloheptylethyl)amino]ethyl]-1H-indol-7-yl] 2-methylpropanoate	1905354: Binding affinity to human recombinant BChE in enzyme-inhibitor complex	ki	0.0002	uM
3-chloro-N-[[2-(diethylaminomethyl)phenyl]methyl]-5-[(4-fluorobenzoyl)amino]benzamide	1886723: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman’s method	ic50	0.0002	uM
[3-[[methyl-[7-(9-oxoxanthen-3-yl)oxyheptyl]amino]methyl]phenyl] N-methylcarbamate	1916856: Inhibition of human serum BChE using butyrylthiocholine as substrate by Ellman’s method	ic50	0.0003	uM
N-[2-(1-benzylpiperidin-4-yl)ethyl]-2-(1-methylindol-3-yl)acetamide	1404012: Inhibition of recombinant human serum BuChE using butyrylthiocholine iodide as substrate pretreated for 5 mins followed by substrate addition measured for 5 mins by Ellman’s method	ic50	0.0003	uM
[3-[[methyl-[5-[(6-oxo-7,8,9,10-tetrahydrobenzo[c]chromen-3-yl)oxy]pentyl]amino]methyl]phenyl] N-heptylcarbamate	1313240: Inhibition of human serum BuChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by Ellman’s method	ic50	0.0003	uM
[3-[[methyl-[3-[(6-oxo-7,8,9,10-tetrahydrobenzo[c]chromen-3-yl)oxy]propyl]amino]methyl]phenyl] N-heptylcarbamate	1313240: Inhibition of human serum BuChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by Ellman’s method	ic50	0.0003	uM
naphthalen-1-yl-[3-(2-piperidin-1-ylethoxy)indazol-1-yl]methanone	1601893: Inhibition of human serum BChE using butyrylthiocholine as substrate by Ellman’s assay	ic50	0.0003	uM
N-[3-[[2-(diethylaminomethyl)phenyl]methylcarbamoyl]phenyl]furan-2-carboxamide	1886723: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman’s method	ic50	0.0003	uM
3,4,5-trimethoxy-N-[8-oxo-8-[2-(1,2,3,4-tetrahydroacridin-9-yl)hydrazinyl]octyl]benzamide	1797052: Cholinesterase Inhibition Assay from Article 10.1021/jm060742o: “Novel heterobivalent tacrine derivatives as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase.”	ic50	0.0003	uM
methyl 2-[8-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]octyl]-6-methoxybenzoate	1831859: Inhibition of human serum BChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by Ellman’s method	ic50	0.0003	uM
N-[[2-(diethylaminomethyl)phenyl]methyl]-3-[(4-fluorobenzoyl)amino]-2-methylbenzamide	1886723: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman’s method	ic50	0.0003	uM
1-(2-oxobutyl)-3-[6-(3,6,7-trihydroxy-5,8-dimethoxy-4-oxochromen-2-yl)-1,3-benzothiazol-2-yl]urea	1950767: Inhibition of BuChE (unknown origin)	ic50	0.0003	uM
N-[4-(1,2,3,4-tetrahydroacridin-9-ylamino)butyl]-N-[3-(1,2,3,4-tetrahydroacridin-9-ylsulfanyl)propyl]acetamide	404429: Inhibition of human recombinant BuChE	ki	0.0003	uM
1H-indol-6-yl N-[2-(1,2,3,4-tetrahydroacridin-9-ylamino)ethyl]carbamate	2088353: Inhibition of human serum BuChE using butyrylthiocholine iodide as substrate incubated for 10 mins followed by substrate addition and measured after 10 mins by DTNB reagent based Ellman’s method	ic50	0.0004	uM
N’-ethyl-N-(1,2,3,4-tetrahydroacridin-9-yl)-N’-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]butane-1,4-diamine	404429: Inhibition of human recombinant BuChE	ki	0.0004	uM
N-[(7-methoxy-1-benzofuran-2-yl)methyl]-N’-(1,2,3,4-tetrahydroacridin-9-yl)hexane-1,6-diamine	1271505: Inhibition of human serum BChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by Ellman’s method	ic50	0.0005	uM
N’,N’-bis[(7-methoxy-1-benzofuran-2-yl)methyl]-N-(1,2,3,4-tetrahydroacridin-9-yl)hexane-1,6-diamine	1271505: Inhibition of human serum BChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by Ellman’s method	ic50	0.0005	uM
[3-[[5-(5H-chromeno[2,3-b]pyridin-8-yloxy)pentyl-methylamino]methyl]phenyl] N-heptylcarbamate	1313240: Inhibition of human serum BuChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by Ellman’s method	ic50	0.0005	uM
N-[5-[2-[3,4-bis(phenylmethoxy)phenyl]ethoxy]pentyl]-1,2,3,4-tetrahydroacridin-9-amine	1564173: Inhibition of human serum BuChe by Ellman’s method	ic50	0.0005	uM
N-[5-[2-(3,4-dimethoxyphenyl)ethoxy]pentyl]-1,2,3,4-tetrahydroacridin-9-amine	1564173: Inhibition of human serum BuChe by Ellman’s method	ic50	0.0005	uM
3,4,5-trimethoxy-N-[7-oxo-7-[2-(1,2,3,4-tetrahydroacridin-9-yl)hydrazinyl]heptyl]benzamide	1797052: Cholinesterase Inhibition Assay from Article 10.1021/jm060742o: “Novel heterobivalent tacrine derivatives as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase.”	ic50	0.0005	uM
5,6-dimethoxy-2-[[7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptylamino]methyl]-2,3-dihydroinden-1-one	1796282: Cholinesterase Inhibition Assay from Article 10.1016/j.bmc.2005.09.029: “Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE.”	ic50	0.0006	uM
5-[[3-(dimethylcarbamoyloxy)phenyl]methyl-methylamino]pentyl (E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate	1846089: Inhibition of human BuchE preincubated for 6 mins followed by substrate addition and measured upto 3 mins using acetylthiocholine iodide as substrate by Ellman’s method	ic50	0.0006	uM
3-bromo-N-[[2-(diethylaminomethyl)phenyl]methyl]-5-[(4-fluorobenzoyl)amino]benzamide	1886723: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman’s method	ic50	0.0006	uM
N-[[2-(diethylaminomethyl)phenyl]methyl]-3-fluoro-5-[(4-fluorobenzoyl)amino]benzamide	1886723: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman’s method	ic50	0.0006	uM
[3-[[methyl-[3-(5-oxochromeno[2,3-b]pyridin-8-yl)oxypropyl]amino]methyl]phenyl] N-heptylcarbamate	1313240: Inhibition of human serum BuChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by Ellman’s method	ic50	0.0007	uM
N-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]-N-[4-(1,2,3,4-tetrahydroacridin-9-ylsulfanyl)butyl]acetamide	404429: Inhibition of human recombinant BuChE	ki	0.0007	uM
N-[2-(1-benzylpiperidin-4-yl)ethyl]-2-(5-bromo-1H-indol-3-yl)acetamide	1404012: Inhibition of recombinant human serum BuChE using butyrylthiocholine iodide as substrate pretreated for 5 mins followed by substrate addition measured for 5 mins by Ellman’s method	ic50	0.0007	uM
N-[3-[[2-[(dipropylamino)methyl]phenyl]methylcarbamoyl]phenyl]thiophene-2-carboxamide	1886723: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman’s method	ic50	0.0007	uM
N-[4-(1,2,3,4-tetrahydroacridin-9-ylamino)butyl]-N-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]acetamide	404429: Inhibition of human recombinant BuChE	ki	0.0007	uM
[3-[[methyl-[5-(2-oxochromen-7-yl)oxypentyl]amino]methyl]phenyl] N-heptylcarbamate	1313240: Inhibition of human serum BuChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition by Ellman’s method	ic50	0.0008	uM
3-[(4-chlorobenzoyl)amino]-N-[[2-(diethylaminomethyl)phenyl]methyl]benzamide	1886723: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman’s method	ic50	0.0008	uM
N’-methyl-N-(1,2,3,4-tetrahydroacridin-9-yl)-N’-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]butane-1,4-diamine	1059722: Inhibition of human butyrylcholine esterase	ki	0.0008	uM
N’-(1,2,3,4-tetrahydroacridin-9-yl)-N-[3-(1,2,3,4-tetrahydroacridin-9-ylsulfanyl)propyl]butane-1,4-diamine	404429: Inhibition of human recombinant BuChE	ki	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Succinylcholine	affects response to substance, increases response to substance, affects hydrolysis, increases hydrolysis, increases metabolic processing (+4 more)	43
Paraoxon	decreases activity, decreases response to substance, decreases reaction, affects binding	17
Sarin	increases hydrolysis, increases reaction, affects reaction, decreases activity, decreases reaction (+4 more)	16
Cocaine	affects hydrolysis, increases hydrolysis, decreases metabolic processing, decreases response to substance, increases chemical synthesis (+3 more)	14
tabun	decreases reaction, affects activity, affects metabolic processing, affects binding, increases reaction (+1 more)	12
VX-agent	affects reaction, decreases activity, decreases reaction, affects cotreatment, decreases response to substance	12
pralidoxime	affects reaction, decreases activity, affects activity, decreases reaction, increases hydrolysis (+1 more)	12
Dichlorvos	affects binding, decreases activity, increases response to substance, decreases reaction	11
Pesticides	decreases activity, affects response to substance, increases abundance	11
Butyrylthiocholine	increases hydrolysis, increases metabolic processing, increases chemical synthesis, decreases reaction	10
Chlorpyrifos	affects cotreatment, decreases activity, decreases reaction, increases activity	8
Organophosphorus Compounds	decreases reaction, affects binding, decreases activity, increases response to substance, affects response to substance (+2 more)	8
Valproic Acid	affects expression, decreases expression, affects cotreatment, increases expression	8
Isoflurophate	decreases activity, decreases reaction, increases hydrolysis	7
Obidoxime Chloride	affects reaction, decreases activity, decreases reaction, increases activity	7
2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide	affects binding, decreases activity, increases abundance, decreases alkylation, increases phosphorylation	6
asoxime chloride	increases activity, affects cotreatment, decreases response to substance, affects reaction, decreases activity (+2 more)	6
cyclohexyl methylphosphonofluoridate	decreases reaction, decreases activity	6
Mivacurium	affects response to substance, increases response to substance	6
Soman	affects binding, increases reaction, decreases response to substance, decreases activity, decreases reaction	6
profenamine	decreases reaction, increases hydrolysis, decreases activity	5
methamidophos	affects binding, decreases activity, decreases reaction	4
Diazinon	affects cotreatment, decreases activity, affects binding	4
Dibucaine	decreases activity, decreases reaction, decreases response to substance, increases metabolic processing	4
Echothiophate Iodide	decreases reaction, increases hydrolysis, decreases activity	4
Organophosphates	decreases activity, affects reaction, decreases reaction, affects response to substance, affects binding	4
Tacrine	decreases activity	4
methylmercuric chloride	decreases expression, affects cotreatment	3
trichostatin A	affects cotreatment, increases expression	3
butyrylcholine	decreases hydrolysis, increases hydrolysis, decreases reaction	3

ChEMBL screening assays

1172 unique, capped per target: 1162 binding, 9 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000390	Binding	Inhibition of human plasma BChE after 20 mins by Ellman’s method	Synthesis and biological evaluation of (-)- and (+)-debromoflustramine B and its analogues as selective butyrylcholinesterase inhibitors. — J Med Chem
CHEMBL3283248	ADMET	Stability of the compound assessed as butyrylcholine esterase (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
CHEMBL4616999	Functional	In-vivo inhibition of BuChE in human brain at 0.6 mg/kg, ip relative to control	Propargylamine-derived multi-target directed ligands for Alzheimer’s disease therapy. — Bioorg Med Chem Lett

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9YH	Ubigene HeLa BCHE KO	Cancer cell line	Female
CVCL_E0TS	Ubigene Hep G2 BCHE KO	Cancer cell line	Male
CVCL_SE83	HAP1 BCHE (-) 1	Cancer cell line	Male
CVCL_SE84	HAP1 BCHE (-) 2	Cancer cell line	Male
CVCL_SE85	HAP1 BCHE (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01205867	PHASE1	COMPLETED	Study to Investigate the Safety and Tolerability of AZD8848 in Butyrylcholinesterase Deficient Subjects
NCT03290859	Not specified	COMPLETED	Race-Specific Propofol Titration to Effect for Procedural Sedation
NCT03415607	Not specified	UNKNOWN	Comparison on Succinylcholine Onset Time Assessed by Train of Four Stimulation Versus Clinical Judgment During Rapid Sequence Induction of Anesthesia
NCT03843580	Not specified	COMPLETED	Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) Could Decrease the Incidence of Oxygen Desaturation During Suspension Laryngoscopy: a Randomized Controlled Trial (Optilaryngo)
NCT05550584	Not specified	COMPLETED	High Flow Oxygen During Operative Hysteroscopy.
NCT06707532	Not specified	RECRUITING	The Potential Protective Effect of Using Muscle Relaxants During Electroporation Ablation (PFA)