MT1 Inhibitors
5 drugsAbout MT1
The Melatonin Receptor Type 1 (MT1) is a G protein-coupled receptor crucial for regulating circadian rhythms and sleep-wake cycles. As a key component of the body's internal clock, MT1 modulates neuronal activity and hormone secretion in response to melatonin.
Human genetic studies provide moderate support for MT1 as a therapeutic target, with variants linked to alcohol drinking (score 0.45) and urethral syndrome (score 0.38). This suggests that modulating MT1 activity could influence these conditions.
MT1 is targeted by three FDA-approved small molecule drugs: HETLIOZ, TASIMELTEON and HETLIOZ LQ. These drugs, developed by Apotex and VANDA PHARMS INC, fall into the 'other' therapeutic area category.
MT1 Genetic Evidence Moderate
Genetic evidence offers moderate support for MT1's role in diseases like alcohol drinking (0.45).
Further research into the genetic basis of MT1-related conditions could reveal novel therapeutic opportunities.
Evidence Across Diseases
10 totalGWAS and other genetic studies link MTNR1A to 10 diseases.
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 MT1 Drugs
Apotex and VANDA PHARMS INC are the only companies with approved MT1-targeting drugs.
The limited number of players suggests a market with potential for new entrants.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| TASIMELTEON | Teva | 2022 | 1 |
| HETLIOZ LQ | VANDA PHARMS INC | 2020 | 1 |
MT1 Drug Modality Landscape
Modalities
Routes of Administration
MT1 is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like biologics could diversify the therapeutic landscape for MT1.
MT1 Clinical Trials 49 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on MT1. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 13 | 13 | 0 | 0 | 100% |
| Phase 2 | 7 | 6 | 1 | 0 | 86% |
| Phase 3 | 13 | 5 | 5 | 3 | 50% |
| Phase 4 | 16 | 10 | 4 | 2 | 71% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved MT1 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting MT1. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
MT1 Drug Approval Timeline (2005 - 2022)
The first MT1 drug was approved in 2014, with the most recent in 2022.
The recent approval suggests continued interest and potential for further drug development in this area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 4 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: 23 (4 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 MT1. A trial counts if an approved drug acting on MT1 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.