M1 Inhibitors
5 drugsAbout M1
The M1 receptor (CHRM1) is a muscarinic acetylcholine receptor subtype involved in various physiological processes. As a G protein-coupled receptor, it mediates the effects of acetylcholine in the central and peripheral nervous systems.
Human genetic studies provide weak support for M1 as a therapeutic target, with variants linked to insomnia (score 0.22) and corneal ulcer (score 0.19). Strong eQTL/pQTL signals suggest potential regulatory mechanisms (max H4: 0.97).
M1 is targeted by 5 FDA-approved small molecule drugs, including INCRUSE ELLIPTA, SPIRIVA RESPIMAT, TUDORZA PRESSAIR, YUPELRI, and DARIFENACIN HYDROBROMIDE. Four drugs are approved for respiratory conditions, while one targets another therapeutic area.
Strategic Insights
ℹ️ How we calculate- White space opportunity in Bladder Cancer with only 1 trials.
Human Genetic Evidence
Genetic evidence for M1 is weak, with a maximum score of 0.22 for insomnia.
Low genetic support suggests higher risk in clinical development, requiring careful patient stratification.
Evidence Across Diseases
2 totalGWAS and other genetic studies link CHRM1 to 2 diseases.
🔗 Colocalization Evidence 2 strong
max H4: 0.97eQTL/pQTL signals for CHRM1 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
Five companies have approved M1-targeting drugs, including GSK, Alembic, and Boehringer Ingelheim.
The presence of multiple established players indicates a competitive market with moderate entry barriers.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| TUDORZA PRESSAIR | AZURITY | 2012 | 1 |
| INCRUSE ELLIPTA | GSK | 2014 | 1 |
Drug Modality Landscape
Modalities
Routes of Administration
M1 is amenable to small molecule drugs, with oral options available for convenient dosing.
Consider exploring alternative modalities like antibodies or peptides to differentiate from existing therapies.
Clinical Trials 283 trials
Completion by Phase
| Phase | Total | Completed | Failed | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 45 | 37 | 1 | 7 | 97% |
| Phase 2 | 57 | 46 | 6 | 5 | 88% |
| Phase 3 | 120 | 109 | 4 | 7 | 96% |
| Phase 4 | 61 | 51 | 8 | 2 | 86% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Drug Approval Timeline (2012 - 2025)
The first M1-targeting drug was approved in 2012, and the most recent in 2018.
The relatively short approval span suggests a potentially saturated market with limited recent innovation.
Pro Intelligence Preview
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
- • 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 144 clinical trials targeting M1.
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