MEK2 Inhibitors
5 drugsAbout MEK2
Mitogen-activated protein kinase kinase 2 (MEK2) is a protein kinase in the MAPK/ERK pathway, regulating cell growth, proliferation, and survival. As a key signaling node, MEK2 has become an important drug target, especially in oncology.
Human genetics provide strong validation for MEK2 as a therapeutic target (score 0.93), with variants linked to rasopathy, cardiofaciocutaneous syndrome, and Noonan syndrome. Inhibition is likely beneficial based on genetic evidence.
MEK2 is targeted by 5 FDA-approved small molecule drugs including MEKINIST, COTELLIC, and MEKTOVI, primarily in oncology. These drugs are developed by Novartis, Roche, AstraZeneca, SPRINGWORKS, and ARRAY BIOPHARMA INC.
MEK2 Genetic Evidence Strong
MEK2 has strong genetic support with a max score of 0.93 linking it to multiple diseases.
Strong genetic support suggests a higher probability of clinical success for MEK2-targeted therapies.
💡 Why inhibition?
- • Gain-of-function variants increase disease risk — blocking overactivity may help
- • 100% directional consistency across 1 traits
- • Strong signal in genetic, familial or congenital disease, integumentary system disease, cardiovascular disease pathways
Cross-Disease Effects
Trade-off: LowDirection of Effect
100% alignedEvidence Across Diseases
9 totalGWAS and other genetic studies link MAP2K2 to 9 diseases.
Gain-of-function causes disease; inhibition may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for MAP2K2 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 MEK2 Drugs
Five companies have approved MEK2-targeting drugs, indicating a moderately competitive landscape.
Consider partnerships or acquisitions to consolidate market share in the MEK2 inhibitor space.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| COTELLIC | Roche | 2015 | 2 |
| GOMEKLI | SPRINGWORKS | 2025 | 1 |
MEK2 Drug Modality Landscape
Modalities
Routes of Administration
MEK2 is amenable to small molecule drugs, with oral options available for convenient dosing.
Explore alternative modalities like PROTACs or biologics to differentiate from existing therapies.
MEK2 Clinical Trials 450 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on MEK2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 204 | 98 | 51 | 53 | 66% |
| Phase 2 | 211 | 73 | 43 | 95 | 63% |
| Phase 3 | 30 | 11 | 4 | 15 | 73% |
| Phase 4 | 5 | 0 | 1 | 4 | 0% |
Top Sponsors
By Modality
Top Conditions
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved MEK2 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting MEK2. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
MEK2 Drug Approval Timeline (2013 - 2025)
The first MEK2-targeting drug was approved in 2013, with the most recent in 2025.
The continued approval of MEK2 inhibitors suggests ongoing opportunity, but market saturation may be approaching.
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
- • Sponsors: 156 (33 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 MEK2. A trial counts if an approved drug acting on MEK2 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.