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Protein / target

Acetylcholinesterase

Encoded byACHEP22303Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
27
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Protein homodimerization

Strongest disease association

Alzheimer's Disease

Via encoding gene ACHE · Clinical evidence · score 0.63

Therapeutic position

Established drug target

Small molecules

Research activity

Emerging research

9 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction.

View complete UniProt function annotation

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

Subcellular location

SynapseSecretedCell membraneNucleus
Domains and Gene Ontology detail (32)

Gene Ontology

  • Cbasement membrane
  • Ccell surface
  • Cextracellular region
  • Cextracellular space
  • CGolgi apparatus
  • Cmembrane
  • Cneuromuscular junction
  • Cnucleus
  • Cperinuclear region of cytoplasm
  • Cplasma membrane
  • Cside of membrane
  • Csynapse

614 aa · 68 kDa · 4 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingUniProt · GO
View supporting evidence

Synaptic signalling

  • ·Synapse
  • ·synapse
  • ·negative regulation of synaptic transmission, cholinergic
  • ·synapse assembly
View underlying pathways (3)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

COLQAPPCHATGPCPD1CHKAMAOBCHKBPHOSPH…HSPG2DOK7ACHE

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Approved medicines with mapped indications

2 medicines · 4 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Alzheimer's Disease1 medicine
Dementia1 medicine
Glaucoma1 medicine
Parkinson's Disease1 medicine

27 medicines meet Open Targets' target-level approved-medicine definition; the 2 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

2

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Isoflurophate
Narrow target profileApprovedInhibitor

Acetylcholinesterase inhibitor

Indicated for Glaucoma

Direct interaction with this protein · Only this protein recorded as a target

rivastigmine
ApprovedInhibitor

Cholinesterases; ACHE & BCHE inhibitor

Indicated for Alzheimer's Disease, Dementia, Parkinson's Disease

Acts on a complex — shared with BCHE · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene ACHE

Gene-level evidence surfaced through the gene ACHEthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Parkinson's Disease
0.80Well supported

Clinical evidence dominant · Open Targets 0.62

Myasthenia Gravis
0.79Well supported

Clinical evidence dominant · Open Targets 0.61

Alzheimer's Disease
0.78Well supported

Clinical evidence dominant · Open Targets 0.63

Dementia
0.77Well supported

Clinical evidence dominant · Open Targets 0.63

Glaucoma
0.68Moderately supported

Clinical evidence dominant · Open Targets 0.55

View evidence synthesis (5)
Parkinson's DiseaseWell supported
0.80
agreement 0.690.92
Clinical70%Animal model18%Literature12%RNA expression0%

Open Targets aggregate 0.62 · 4 independent evidence families

Myasthenia GravisWell supported
0.79
agreement 0.660.92
Clinical75%Animal model20%Literature5%

Open Targets aggregate 0.61 · 3 independent evidence families

Alzheimer's DiseaseWell supported
0.78
agreement 0.630.94
Clinical84%Literature16%

Open Targets aggregate 0.63 · 2 independent evidence families

DementiaWell supported
0.77
agreement 0.620.93
Clinical87%Literature13%

Open Targets aggregate 0.63 · 2 independent evidence families

GlaucomaModerately supported
0.68
agreement 0.520.83
Clinical97%Literature3%

Open Targets aggregate 0.55 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Alzheimer's Disease0.63
Dementia0.63
Parkinson's Disease0.62
Myasthenia Gravis0.61
Glaucoma0.55
Neurodegenerative Diseases0.53
Poisoning0.51
Dyspepsia0.49
Gastrointestinal disease0.46

Drug development

32 compounds recorded · 27 approved · 1 in clinical development · 4 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
BENZGALANTAMINEUnknown
GALANTAMINEApproval
PROPANIDIDUnknown
NEOSTIGMINE METHYLSULFATEApproval
MINAPRINEApproval
TACRINEApproval
ITOPRIDEApproval
DEMECARIUM BROMIDEApproval
HUPERZINE AApproval
ACOTIAMIDE HYDROCHLORIDEApproval

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

increased salivationLynch et al. (2017)deathLynch et al. (2017)bronchoconstrictionLynch et al. (2017)muscle relaxationLynch et al. (2017)comaLynch et al. (2017)decreased blood pressureBowes et al. (2012)increased defecationLynch et al. (2017)increased respiratory secretionsBowes et al. (2012)foot dropLynch et al. (2017)vomitingLynch et al. (2017)peripheral neuropathyLynch et al. (2017)increased urine excretionLynch et al. (2017)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

SUSPENDED · via rivastigmine · NCT00102856

TERMINATED · via rivastigmine · NCT00102284

TERMINATED · via rivastigmine · NCT02374567

COMPLETED · via rivastigmine · NCT01073319

COMPLETED · via rivastigmine · NCT01030692

ClinicalTrials.gov via the drug-target graph.

What's happening now

9

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. New publication2024-01-17
    Neuroprotectant Activity of Novel Water-Soluble Synthetic Neurosteroids on Organophosphate Intoxication and Status Epilepticus-Induced Long-Term Neurological Dysfunction, Neurodegeneration, and Neuroinflammation.

    The Journal of pharmacology and experimental therapeutics · 2024 · 14 citations · Europe PMC · via Isoflurophate

  2. New publication2024-01-17
    Sex Differences in Organophosphate Model of Benzodiazepine-Refractory Status Epilepticus and Neuronal Damage.

    The Journal of pharmacology and experimental therapeutics · 2024 · 12 citations · Europe PMC · via Isoflurophate

  3. New publication2024-01-17
    A Pediatric Rat Model of Organophosphate-Induced Refractory Status Epilepticus: Characterization of Long-Term Epileptic Seizure Activity, Neurologic Dysfunction and Neurodegeneration.

    The Journal of pharmacology and experimental therapeutics · 2024 · 10 citations · Europe PMC · via Isoflurophate

  4. Regulatory approval2009-12-11

    Approval: Rivastigmine 1 A Pharma (EMA)

    ema · regulatory · ema · via rivastigmine

  5. Regulatory approval2009-12-11

    Approval: Rivastigmine Hexal (EMA)

    ema · regulatory · ema · via rivastigmine

  6. Regulatory approval2009-12-10

    Approval: Rivastigmine Sandoz (EMA)

    ema · regulatory · ema · via rivastigmine

  7. Regulatory approval2009-05-11

    Approval: Nimvastid (EMA)

    ema · regulatory · ema · via rivastigmine

  8. Regulatory approval1998-12-04

    Approval: Prometax (EMA)

    ema · regulatory · ema · via rivastigmine

  9. Regulatory approval1998-05-11

    Approval: Exelon (EMA)

    ema · regulatory · ema · via rivastigmine

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.

Research activity

9 papers · to 2025

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Recent

Europe PMC papers linked directly to this protein.