mTOR Inhibitors
11 drugsAbout mTOR
The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase regulating cell growth, proliferation, metabolism, and survival. As a master regulator of these processes, mTOR is a significant drug target.
Human genetic studies provide strong validation for mTOR as a therapeutic target (max score 0.93), with variants linked to isolated focal cortical dysplasia type II. Loss-of-function variants are associated with increased disease risk, suggesting activation may be beneficial.
mTOR is targeted by 9 FDA-approved small molecule drugs, including FYARRO, SIROLIMUS, TEMSIROLIMUS, and AFINITOR. Four drugs are used in oncology, while five address other therapeutic needs.
mTOR Genetic Evidence Strong
Genetic evidence strongly supports mTOR as a drug target, with a maximum score of 0.93.
Strong genetic support suggests increased probability of clinical success, warranting further investment in mTOR-targeting therapies.
💡 Why activation?
- • Loss-of-function variants increase disease risk (OR > 1) — restoring function may help
- • 100% directional consistency across 1 traits
- • Strong signal in genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
12 totalGWAS and other genetic studies link MTOR to 12 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 0.98eQTL/pQTL signals for MTOR 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 mTOR Drugs
Six companies have approved mTOR-targeting drugs, with Novartis leading with multiple indications for AFINITOR.
The competitive landscape is moderately concentrated, suggesting potential entry barriers for new players.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| AFINITOR DISPERZ | Novartis | 2012 | 7 |
| SIROLIMUS | Apotex | 2014 | 2 |
| HYFTOR | NOBELPHARMA | 2022 | 2 |
| TEMSIROLIMUS | ACCORD HLTHCARE | 2018 | 1 |
| FYARRO | AADI | 2021 | 1 |
| ZORTRESS | Novartis | 2010 | 1 |
| MYCOPHENOLATE MOFETIL | STRIDES PHARMA | 2008 | - |
| EVEROLIMUS | Teva | 2018 | - |
mTOR Drug Modality Landscape
Modalities
Routes of Administration
mTOR is amenable to small molecule drugs, with oral options available for convenient dosing.
The modality landscape is saturated with small molecules, suggesting an opportunity for novel modalities like antibodies or biologics.
mTOR Clinical Trials 930 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on mTOR. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 359 | 219 | 66 | 73 | 77% |
| Phase 2 | 402 | 206 | 90 | 104 | 70% |
| Phase 3 | 91 | 47 | 13 | 31 | 78% |
| Phase 4 | 78 | 56 | 13 | 9 | 81% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
7 Phase 3 trials testing approved mTOR drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting mTOR. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
mTOR Drug Approval Timeline (1999 - 2022)
The first mTOR-targeting drug, RAPAMUNE, was approved in 1999, with the most recent, HYFTOR, approved in 2022.
The 24-year approval span indicates a mature target, but recent approvals suggest continued innovation and market potential.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 8 companies competing
- • Market share by company
Full Drug Portfolio
- • All 11 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 11-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 374 (67 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 mTOR. A trial counts if an approved drug acting on mTOR 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.