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).
Cholinesterase 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 Cholinesterase 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 |
|---|---|---|---|
| RIVASTIGMINE TARTRATE | Sun Pharma | 2007 | 2 |
| NEOSTIGMINE METHYLSULFATE | Fresenius Kabi | 2015 | 1 |
| BLOXIVERZ | EXELA PHARMA | 2013 | 1 |
Cholinesterase 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.
Cholinesterase Clinical Trials 176 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Cholinesterase. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 27 | 24 | 2 | 1 | 92% |
| Phase 2 | 39 | 28 | 1 | 8 | 97% |
| Phase 3 | 25 | 22 | 2 | 1 | 92% |
| Phase 4 | 85 | 72 | 10 | 3 | 88% |
Top Sponsors
By Modality
Top Conditions
Cholinesterase Drug Approval Timeline (1955 - 2015)
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
- • Sponsors: 114 (13 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 Cholinesterase. A trial counts if an approved drug acting on Cholinesterase 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.