Acetylcholinesterase Inhibitors
5 drugsAbout Acetylcholinesterase
Acetylcholinesterase (AChE) is an enzyme that hydrolyzes acetylcholine, terminating its signaling and regulating nerve impulse transmission. It plays a crucial role in the nervous system, particularly in the central nervous system (CNS).
AChE is a significant drug target with strong genetic support (max score 0.78). Genetic evidence links ACHE to skeletal system abnormalities (score 0.78), skin cancer (0.54), and hair color (0.53), supporting therapeutic intervention.
Five FDA-approved drugs target AChE, including ARICEPT, ZUNVEYL, and DUODOTE. All five drugs are small molecules, primarily indicated for CNS disorders.
Acetylcholinesterase Genetic Evidence Strong
Genetic evidence strongly supports ACHE's role in disease, with a max score of 0.78.
Strong genetic support suggests increased likelihood of clinical success for AChE-targeting drugs.
Evidence Across Diseases
7 totalGWAS and other genetic studies link ACHE to 7 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for ACHE colocalize with these GWAS traits, providing causal evidence that gene expression changes drive disease risk.
Understanding these scores
Association Score (0-1): Combines all evidence types (genetic, literature, drugs, animal models). Higher = more evidence linking target to disease. This is a ranking heuristic, not a confidence score.
L2G Score: Open Targets uses a machine learning model (Locus-to-Gene) to predict which gene is causal at each GWAS locus. L2G=0.5 means ~50% probability of being the causal gene. Only associations with L2G > 0.05 are included.
Odds Ratio (OR): From gene burden studies (UK Biobank, AstraZeneca PheWAS). Measures how loss-of-function variants affect disease risk. OR<1 = protective (inhibiting target may help), OR>1 = risk (losing function causes disease).
Beta (β): Effect size for continuous traits. β<0 = protective, β>0 = risk.
Clinical Translation (~1.8x): Based on Nelson et al. 2015: drug targets with genetic evidence have ~2x higher success rates in clinical trials. We estimate: Strong support (score ≥0.7) → ~1.8x, Moderate (0.3-0.7) → ~1.3x, Weak → baseline.
Colocalization (H4): Tests whether a GWAS signal and an eQTL/pQTL signal share the same causal variant. H4 is the posterior probability that both traits are associated AND share a causal variant. H4 > 0.8 = strong evidence that gene expression/protein levels drive disease risk. This links genetic variation → gene expression → disease, supporting the target-disease connection.
Top Acetylcholinesterase Drugs
Five companies have approved drugs targeting AChE, including EISAI INC and AbbVie.
The relatively low number of companies suggests moderate barriers to entry in this market.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| MEMANTINE HYDROCHLORIDE AND DONEPEZIL HYDROCHLORIDE | ANI PHARMS | 2017 | 1 |
| NAMZARIC | AbbVie | 2014 | 1 |
Acetylcholinesterase Drug Modality Landscape
Modalities
Routes of Administration
Acetylcholinesterase is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or biologics could provide a competitive advantage.
Acetylcholinesterase Clinical Trials 278 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Acetylcholinesterase. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 70 | 54 | 9 | 7 | 86% |
| Phase 2 | 95 | 55 | 13 | 27 | 81% |
| Phase 3 | 51 | 29 | 7 | 15 | 81% |
| Phase 4 | 62 | 48 | 7 | 7 | 87% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Acetylcholinesterase Drug Approval Timeline (1996 - 2024)
Alzheimer's Disease
The first drug, ARICEPT, was approved in 1996, with the most recent, ZUNVEYL, approved in 2024.
The 29-year span suggests continued interest and potential for further innovation in AChE-targeting therapies.
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Deep insights for drug target analysis
Competitive Landscape
- • 5 companies competing
- • Market share by company
Full Drug Portfolio
- • All 5 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 5-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 182 (50 companies)
- • Completion rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Count Trials
- Trials: phase 1-4 interventional trials on ClinicalTrials.gov that started in 2008 or later and test an FDA-approved drug acting on Acetylcholinesterase. A trial counts if an approved drug acting on Acetylcholinesterase is in any arm, including as a comparator, and a trial that tests two such drugs counts once. Trials that test only unapproved drugs are not counted. A trial listed as phase 1/2 counts as phase 1, and phase 2/3 as phase 2.
- Active: recruiting, not yet recruiting, enrolling by invitation, or active and no longer recruiting.
- Completion rate: of the trials that have ended, the share marked Completed rather than Terminated or Withdrawn. Completed means the trial ended as planned; it does not mean the drug worked. Suspended trials are not counted as ended.
- Stopped: terminated or withdrawn. Trials stop for many reasons, including slow enrolment and business decisions, not only safety or efficacy.
- Sponsors: the lead sponsor of each trial. Companies are the sponsors ClinicalTrials.gov classes as industry; the rest are universities, hospitals, cooperative groups, government bodies and individuals.