Cholinesterase Inhibitors
6 drugsAbout Cholinesterase
Cholinesterase (ACHE) is an enzyme that breaks down acetylcholine, a key neurotransmitter involved in muscle movement, memory, and other vital functions. Inhibiting ACHE increases acetylcholine levels, offering therapeutic benefits by modulating cholinergic neurotransmission. It is encoded by the ACHE gene (ENSG00000087085).
Human genetic studies provide strong validation for ACHE as a therapeutic target (max score 0.78), with variants linked to skeletal system abnormalities (0.78), skin cancer (0.54), and hair color (0.53). Colocalization analysis reveals 20 strong eQTL/pQTL signals (max H4: 1.00).
ACHE is targeted by 6 FDA-approved small molecule drugs, including Rivastigmine Tartrate, Prevduo, and Mestinon. These drugs are used across CNS and other therapeutic areas, with approvals spanning from 1955 (Mestinon) to 2023 (Prevduo).
Strategic Insights
ℹ️ How we calculate- White space opportunity in Bladder Cancer with only 2 trials.
Human Genetic Evidence Strong
Genetic evidence strongly supports ACHE as a drug target, with a maximum score of 0.78.
The strong genetic support suggests a higher probability 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 Drugs
Six companies have approved drugs targeting ACHE, including Alembic Pharms Ltd, Exela Pharma, and Bausch.
The relatively low number of companies suggests moderate barriers to entry in this market.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| BLOXIVERZ | EXELA PHARMA | 2013 | 1 |
| NEOSTIGMINE METHYLSULFATE | AVET LIFESCIENCES | 2015 | 1 |
| MESTINON | BAUSCH | 1955 | 1 |
Drug Modality Landscape
Modalities
Routes of Administration
Cholinesterase 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.
Clinical Trials 263 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 47 | 35 | 3 | 9 | 92% |
| Phase 2 | 55 | 37 | 3 | 12 | 93% |
| Phase 3 | 69 | 56 | 5 | 8 | 92% |
| Phase 4 | 92 | 75 | 11 | 5 | 87% |
Top Sponsors
By Modality
Top Conditions
Drug Approval Timeline (1955 - 2023)
Mild-to-moderate dementia of the Alzheimer’s type
Nondepolarizing neuromuscular blockade (post-surgery)
The approval timeline for ACHE-targeting drugs spans 69 years, from 1955 to 2023.
The continued approvals indicate sustained interest and potential for further development in this area.
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Deep insights for drug target analysis
Competitive Landscape
- • 6 companies competing
- • Market share by company
Full Drug Portfolio
- • All 6 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 6-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Competition: High (15 sponsors)
- • White space: 10 underexplored indications
- • Success rates by condition
Full summary • All drugs • Genetic evidence • Trials • Timeline
How We Calculate These Metrics
Target Attractiveness Score
A 0-100 score based on trial activity, sponsor diversity, and completion rates. Calculated from 184 clinical trials targeting Cholinesterase.
Completion rate: Percentage of trials that reached their planned endpoint. Trials terminated early, withdrawn, or suspended are not counted—these often indicate safety issues, lack of efficacy, or strategic pivots.
- Highly Attractive (80+): High trial activity, many sponsors, strong completion rates
- Attractive (60-79): Good trial activity and validation
- Moderate (40-59): Moderate interest from sponsors
- Low (under 40): Limited trial activity or validation concerns
Strategic Insights
Auto-generated insights based on trial analytics including competition intensity, white space opportunities, modality shifts, and failure patterns. We analyze trial sponsors, phases, indications, and outcomes.
Risk Signals
- High Competition: Many sponsors competing for this target (may reduce market opportunity)
- High Failure Risk: Low trial completion rates suggest development challenges
- Low Validation: Limited trial activity or poor outcomes indicate uncertain viability
- White Space Available: Underexplored indications present opportunities