Donepezil

Summary

Donepezil (CHEMBL502) is an approved small molecule (ATC N06DA02) targeting ACHE; indicated across 27 conditions including dementia and stroke disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06DA02
• Targets: 1 (ACHE)
• Indications: 27 conditions
• Clinical trials: 239
• Chemistry: 379.5 Da · C24H29NO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL502
Name	Donepezil
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3152
ChEBI	CHEBI:145499
ATC	N06DA02
Molecular formula	C24H29NO3
Molecular weight	379.5
InChIKey	ADEBPBSSDYVVLD-UHFFFAOYSA-N

SMILES: COC1=C(C=C2C(=C1)CC(C2=O)CC3CCN(CC3)CC4=CC=CC=C4)OC

IUPAC name: 2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-2,3-dihydroinden-1-one

ChEBI definition: A member of the class of indanones that is 5,6-dimethoxyindan-1-one which is substituted at position 2 by an (N-benzylpiperidin-4-yl)methyl group.

Also known as: D-797, Donaz, Donepezil, Donepezilo, donepezil, Aricept, SID50112790, DONEPEZIL, DONEPEZIL HYDROCHLORIDE, Donepezil; Aricept

Parent form; salt/anhydrous children: CHEMBL1678, CHEMBL2171854, CHEMBL2337271

Patent coverage: 12,103 distinct patent families (43,493 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 42,764 (98%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
ACHE	acetylcholinesterase (Yt blood group)	Inhibition	8.3	9.6%	P22303

Broader ChEMBL bioactivity targets: 39 (assay-derived). Sample: ATP-binding cassette sub-family C member 4, cGMP-specific 3’,5’-cyclic phosphodiesterase, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Cholinesterase, Alpha-2C adrenergic receptor, Muscarinic acetylcholine receptor M5, Amine oxidase [flavin-containing] B, Voltage-gated L-type calcium channel, Muscarinic acetylcholine receptor M2.

Bioactivity

ChEMBL activities: 654 potent at pChembl ≥ 5 of 690 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P37136	8.77	IC50	1.7	nM	CHEMBL_ACT_194436
ACHE	8.7	IC50	2	nM	CHEMBL_ACT_12633739
P37136	8.7	IC50	2	nM	CHEMBL_ACT_23175986
ACHE	8.63	IC50	2.33	nM	CHEMBL_ACT_236925
P23795	8.54	Ki	2.9	nM	CHEMBL_ACT_124711
P23795	8.54	Ki	2.9	nM	CHEMBL_ACT_1405447
ACHE	8.41	IC50	3.9	nM	CHEMBL_ACT_25523610
ACHE	8.4	IC50	4	nM	CHEMBL_ACT_24776386
P23795	8.38	IC50	4.2	nM	CHEMBL_ACT_12633713
O42275	8.37	Ki	4.24	nM	CHEMBL_ACT_15227890
P81908	8.34	IC50	4.6	nM	CHEMBL_ACT_18517481
ACHE	8.3	IC50	5	nM	CHEMBL_ACT_22485753
ACHE	8.3	IC50	5	nM	CHEMBL_ACT_29231253
P37136	8.3	IC50	5	nM	CHEMBL_ACT_7962822
P32738	8.28	IC50	5.3	nM	CHEMBL_ACT_1092637
P21836	8.27	IC50	5.4	nM	CHEMBL_ACT_24909875
ACHE	8.25	IC50	5.59	nM	CHEMBL_ACT_19140482
P37136	8.24	IC50	5.7	nM	CHEMBL_ACT_1206408
ACHE	8.24	IC50	5.7	nM	CHEMBL_ACT_12664641
P21836	8.24	IC50	5.7	nM	CHEMBL_ACT_18124324
ACHE	8.24	IC50	5.7	nM	CHEMBL_ACT_18317112
ACHE	8.24	IC50	5.7	nM	CHEMBL_ACT_18392537
ACHE	8.24	IC50	5.7	nM	CHEMBL_ACT_18701672
ACHE	8.24	IC50	5.7	nM	CHEMBL_ACT_18996933
ACHE	8.24	IC50	5.7	nM	CHEMBL_ACT_19371186
P37136	8.24	IC50	5.7	nM	CHEMBL_ACT_2351227
ACHE	8.22	IC50	6	nM	CHEMBL_ACT_15169093
ACHE	8.22	IC50	6	nM	CHEMBL_ACT_15213049
ACHE	8.22	IC50	6	nM	CHEMBL_ACT_15219563
ACHE	8.22	IC50	6	nM	CHEMBL_ACT_16831102

Target pathways

Aggregated over 1 target gene(s): ACHE.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Neurotransmitter clearance	1	ACHE
Transmission across Chemical Synapses	1	ACHE
Neuronal System	1	ACHE
Metabolism	1	ACHE
Synthesis of PC	1	ACHE
Glycerophospholipid biosynthesis	1	ACHE
Phospholipid metabolism	1	ACHE
Peptide hormone metabolism	1	ACHE
Metabolism of proteins	1	ACHE
Synthesis, secretion, and deacylation of Ghrelin	1	ACHE
Metabolism of lipids	1	ACHE

Dominant GO biological processes

GO term	Targets
acetylcholine catabolic process in synaptic cleft	1
regulation of receptor recycling	1
osteoblast development	1
acetylcholine catabolic process	1
cell adhesion	1
nervous system development	1
synapse assembly	1
receptor internalization	1
negative regulation of synaptic transmission, cholinergic	1
amyloid precursor protein metabolic process	1
positive regulation of protein secretion	1
retina development in camera-type eye	1
acetylcholine receptor signaling pathway	1
positive regulation of cold-induced thermogenesis	1

Indications & clinical

Indications

27 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
dementia	4	MONDO:0001627	HP:0000726
stroke disorder	3	MONDO:0005098	EFO:0000712
vascular dementia	3	MONDO:0004648	EFO:0004718
anxiety	3	MONDO:0011918	EFO:0005230
aphasia	3	MONDO:0000598	HP:0002381
depressive disorder	3	MONDO:0002050	MONDO:0002050
Alzheimer disease	3	MONDO:0004975	MONDO:0004975
Parkinson disease	3	MONDO:0005180	MONDO:0005180
multiple sclerosis	3	MONDO:0005301	MONDO:0005301
neoplasm	3	MONDO:0005070	MONDO:0004992
cocaine dependence	2	MONDO:0005186	EFO:0002610
autism spectrum disorder	2	MONDO:0005258	EFO:0003756
nicotine dependence	2	MONDO:0008575	EFO:0003768
neuralgia	2	MONDO:0021667	EFO:0005762
progressive supranuclear palsy	2	MONDO:0019037	Orphanet:240071
delirium	2	MONDO:0045057	EFO:0009267
injury	2	MONDO:0021178	EFO:0000546
type 2 diabetes mellitus	2	MONDO:0005148	MONDO:0005148
fragile X syndrome	2	MONDO:0010383	MONDO:0010383
skin disorder	1	MONDO:0005093	EFO:0000701
amblyopia	1	MONDO:0001020	MONDO:0001020
central nervous system disorder	1	MONDO:0002602	EFO:0009386
sensorineural hearing loss disorder	0	MONDO:0020678	EFO:1001176

4 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 239.

Phase distribution

Phase	Trials
PHASE2	57
PHASE1	54
PHASE4	51
Not specified	36
PHASE3	29
EARLY_PHASE1	6
PHASE2/PHASE3	3
PHASE1/PHASE2	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07153991	PHASE4	ACTIVE_NOT_RECRUITING	Efficacy of Donepezil in Patients With Chronic Tinnitus
NCT00018278	PHASE4	COMPLETED	Electrophysiologic Measures of Treatment Response in Alzheimer Disease
NCT00030979	PHASE4	COMPLETED	Donepezil to Treat Dementia in Parkinson’s Disease
NCT00042172	PHASE4	COMPLETED	Treatment for Early Memory Loss
NCT00142324	PHASE4	UNKNOWN	CALM-AD
NCT00165724	PHASE4	COMPLETED	Alzheimer’s Disease Long-term Follow-up Study (ALF Study)
NCT00165750	PHASE4	TERMINATED	Correlation Between Regional Brain Volume and Response to Donepezil Treatment in AD Patients
NCT00165763	PHASE4	COMPLETED	Efficacy and Safety of Donepezil Hydrochloride (Aricept) in Vascular Dementia
NCT00177671	PHASE4	COMPLETED	Antidepressant Medication Plus Donepezil for Treating Late-life Depression
NCT00182845	PHASE4	COMPLETED	Donepezil in the Prevention of Post-Operative Cognitive Decline
NCT00182884	PHASE4	COMPLETED	Donepezil in Preventing Delirium in Hospitalized Elderly
NCT00196690	PHASE4	COMPLETED	Donepezil in Chronic Poststroke Aphasia: a Randomized Controlled Trial
NCT00220896	PHASE4	COMPLETED	Prevention of Postoperative Delirium With Donepezil
NCT00227994	PHASE4	COMPLETED	Acetylcholinesterase Inhibitors to Improve Cognitive Function and Overall Rehabilitation After a Stroke
NCT00230568	PHASE4	COMPLETED	EARTH 413: A Study of Aricept in Hispanic Patients With Mild to Moderate Alzheimer’s Disease (AD)
NCT00267163	PHASE4	COMPLETED	Brain Imaging and Mental Disorders of Aging Intervention
NCT00293176	PHASE4	COMPLETED	The Evaluation of the Efficacy and Safety of Donepezil Hydrochloride in Subjects With Mild Cognitive Impairment (MCI)
NCT00369603	PHASE4	TERMINATED	Functional Brain Imaging of Medication Treatment Response in Mild Alzheimer’s Disease Patients
NCT00381381	PHASE4	COMPLETED	The Clinical Response of Choline Acetyltransferase and Apolipoprotein Epsilon Gene Polymorphisms to Donepezil in Alzheimer’s Disease
NCT00465283	PHASE4	UNKNOWN	Donepezil Double Blind Trial for ECT Memory Disfunction
NCT00477659	PHASE4	COMPLETED	Neural Correlates In Mild Alzheimer’s Disease
NCT00480870	PHASE4	COMPLETED	The Effect of Anticholinesterase Drugs on Sleep in Alzheimer’s Disease Patients
NCT00482001	PHASE4	COMPLETED	Impact of Cholinesterase Inhibitors on Driving Ability in Healthy Older Adults
NCT00505167	PHASE4	COMPLETED	Memantine Versus Donepezil in Early Stages of Alzheimer’s Disease
NCT00619983	PHASE4	TERMINATED	Three Way Interaction Between Gabapentin, Duloxetine, and Donepezil in Patients With Diabetic Neuropathy
NCT00711204	PHASE4	WITHDRAWN	Evaluating The Impact Of Donepezil Hydrochloride (Aricept) On Behavioral And Psychological Symptoms In Patients With Severe Alzheimer’s Disease
NCT00768261	PHASE4	COMPLETED	Corticolimbic Degeneration and Treatment of Dementia
NCT00800553	PHASE4	COMPLETED	fMRI-behavioral Study of Cholinergic Augmentation With Donepezil in Healthy Sleep Deprived Adults
NCT00866060	PHASE4	UNKNOWN	Donepezil and Memantine in Moderate to Severe Alzheimer’s Disease
NCT00912457	PHASE4	UNKNOWN	Donepezil Treatment for Sleep Apnea Patients
NCT01191918	PHASE4	COMPLETED	The Efficacy and Safety of AChE Inhibitor Donepezil As Adjunctive Treatment to Mood Stabilizers in Acute Mania
NCT01490567	PHASE4	UNKNOWN	A Double-blind, Placebo-controlled Trial of Donepezil Adjunctive Treatment for Cognitive Impairment in Schizophrenia
NCT01521117	PHASE4	COMPLETED	The Effect of Donepezil on Gait and Balance in Parkinson’s Disease
NCT01633593	PHASE4	TERMINATED	Treatment of Delirium in the Elderly With Donepezil: a Double-blind, Randomized, Placebo-controlled Clinical Trial
NCT01658228	PHASE4	COMPLETED	Combination Treatment Study for Memory Impairment and Depression
NCT01743976	PHASE4	TERMINATED	Donepezil Compared to Placebo in Patients With Chronic Neuropathic Pain
NCT01822951	PHASE4	WITHDRAWN	Cerebrolysin Compared to Donepezil in Patients With Mild to Moderate Dementia of Alzheimer’s Type (DAT)
NCT01845636	PHASE4	COMPLETED	Olfactory Deficits in MCI as Predictor of Improved Cognition on Donepezil
NCT01849042	PHASE4	UNKNOWN	Effect of Memantine Oral Pump on Language in Patients With Probable Alzheimer’s Disease
NCT01951118	PHASE4	COMPLETED	Olfactory Deficits and Donepezil Treatment in Cognitively Impaired Elderly

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 5 clinical and 61 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

153 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	ACHE
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	ACHE
TADALAFIL	ChEMBL + PubChem	Phase 4 (approved)	ACHE
ALFUZOSIN	ChEMBL	Phase 4 (approved)	ACHE
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ACHE
BERBERINE	ChEMBL	Phase 4 (approved)	ACHE
BOSUTINIB	ChEMBL	Phase 4 (approved)	ACHE
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	ACHE
BUTENAFINE	ChEMBL	Phase 4 (approved)	ACHE
CABERGOLINE	ChEMBL	Phase 4 (approved)	ACHE
CAFFEINE	ChEMBL	Phase 4 (approved)	ACHE
CANNABIDIOL	ChEMBL	Phase 4 (approved)	ACHE
CITALOPRAM	ChEMBL	Phase 4 (approved)	ACHE
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	ACHE
DECAMETHONIUM	ChEMBL	Phase 4 (approved)	ACHE
DECAMETHONIUM BROMIDE	ChEMBL	Phase 4 (approved)	ACHE
DEQUALINIUM	ChEMBL	Phase 4 (approved)	ACHE
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	ACHE
DISULFIRAM	ChEMBL	Phase 4 (approved)	ACHE
DOFETILIDE	ChEMBL	Phase 4 (approved)	ACHE
DYCLONINE	ChEMBL	Phase 4 (approved)	ACHE
EBASTINE	ChEMBL	Phase 4 (approved)	ACHE
ECONAZOLE	ChEMBL	Phase 4 (approved)	ACHE
EDROPHONIUM	ChEMBL	Phase 4 (approved)	ACHE
EDROPHONIUM CHLORIDE	ChEMBL	Phase 4 (approved)	ACHE
EPIRUBICIN	ChEMBL	Phase 4 (approved)	ACHE
ETHOPROPAZINE	ChEMBL	Phase 4 (approved)	ACHE
ETHYLESTRENOL	ChEMBL	Phase 4 (approved)	ACHE
FENOFIBRATE	ChEMBL	Phase 4 (approved)	ACHE
FLAVOXATE	ChEMBL	Phase 4 (approved)	ACHE
FLUOXETINE	ChEMBL	Phase 4 (approved)	ACHE
GALANTAMINE	ChEMBL	Phase 4 (approved)	ACHE
GALLAMINE	ChEMBL	Phase 4 (approved)	ACHE
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	ACHE
HEXAFLUORENIUM	ChEMBL	Phase 4 (approved)	ACHE
ILOPERIDONE	ChEMBL	Phase 4 (approved)	ACHE
IRINOTECAN	ChEMBL	Phase 4 (approved)	ACHE
ISOFLUROPHATE	ChEMBL	Phase 4 (approved)	ACHE
LEVALLORPHAN	ChEMBL	Phase 4 (approved)	ACHE
LORLATINIB	ChEMBL	Phase 4 (approved)	ACHE
LURASIDONE	ChEMBL	Phase 4 (approved)	ACHE
MELPHALAN	ChEMBL	Phase 4 (approved)	ACHE
MEMANTINE	ChEMBL	Phase 4 (approved)	ACHE
MEPTAZINOL	ChEMBL	Phase 4 (approved)	ACHE
METHOXSALEN	ChEMBL	Phase 4 (approved)	ACHE
MICONAZOLE	ChEMBL	Phase 4 (approved)	ACHE
MINAPRINE	ChEMBL	Phase 4 (approved)	ACHE
NAFTOPIDIL	ChEMBL	Phase 4 (approved)	ACHE
NEFAZODONE	ChEMBL	Phase 4 (approved)	ACHE
NEOSTIGMINE	ChEMBL	Phase 4 (approved)	ACHE
NEOSTIGMINE METHYLSULFATE	ChEMBL	Phase 4 (approved)	ACHE
NICERGOLINE	ChEMBL	Phase 4 (approved)	ACHE
NIZATIDINE	ChEMBL	Phase 4 (approved)	ACHE
ORLISTAT	ChEMBL	Phase 4 (approved)	ACHE
OXICONAZOLE	ChEMBL	Phase 4 (approved)	ACHE
PALBOCICLIB	ChEMBL	Phase 4 (approved)	ACHE
PENTAMIDINE	ChEMBL	Phase 4 (approved)	ACHE
PENTOXIFYLLINE	ChEMBL	Phase 4 (approved)	ACHE
PERICIAZINE	ChEMBL	Phase 4 (approved)	ACHE
PHYSOSTIGMINE	ChEMBL	Phase 4 (approved)	ACHE