M1 Inhibitors
7 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.
M1 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 M1 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 |
|---|---|---|---|
| SPIRIVA RESPIMAT | Boehringer Ingelheim | 2014 | 2 |
| TONMYA | TONIX | 2025 | 1 |
| TUDORZA PRESSAIR | AZURITY | 2012 | 1 |
| INCRUSE ELLIPTA | GSK | 2014 | 1 |
M1 Drug Modality Landscape
Modalities
Routes of Administration
M1 is druggable by small molecules, though no oral formulations are currently approved.
Consider exploring alternative modalities like antibodies or peptides to differentiate from existing therapies.
M1 Clinical Trials 190 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on M1. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 20 | 18 | 1 | 1 | 95% |
| Phase 2 | 37 | 31 | 5 | 1 | 86% |
| Phase 3 | 74 | 67 | 6 | 1 | 92% |
| Phase 4 | 59 | 47 | 6 | 6 | 89% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
M1 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
- • 7 companies competing
- • Market share by company
Full Drug Portfolio
- • All 7 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 7-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 61 (31 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 M1. A trial counts if an approved drug acting on M1 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.