Nrf2 Inhibitors
5 drugsAbout Nrf2
Nrf2 (Nuclear factor erythroid 2-related factor 2) is a transcription factor and master regulator of cellular defense. It activates antioxidant and cytoprotective genes, protecting cells from oxidative stress and damage.
Human genetic studies provide strong support for Nrf2 as a therapeutic target (max score 0.88). Variants are linked to immunodeficiency, skeletal abnormalities, and intestinal impaction, supporting modulation of Nrf2 activity for therapeutic benefit.
Nrf2 is targeted by five FDA-approved small molecule drugs, including VUMERITY, TECFIDERA, and DIROXIMEL FUMARATE. These drugs, developed by Biogen, BANNER LIFE SCIENCES, and ZYDUS, are used in CNS disorders and other therapeutic areas.
Nrf2 Genetic Evidence Strong
Nrf2 has strong genetic support with a maximum score of 0.88 linking it to specific diseases.
Strong genetic support suggests a higher probability of clinical success for Nrf2-targeting therapies.
Evidence Across Diseases
3 totalGWAS and other genetic studies link NFE2L2 to 3 diseases.
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for NFE2L2 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 Nrf2 Drugs
Three companies, including Biogen and ZYDUS, have approved Nrf2-targeting drugs.
The competitive landscape indicates moderate market concentration, suggesting potential entry barriers for new players.
Nrf2 Drug Modality Landscape
Modalities
Routes of Administration
Nrf2 is amenable to small molecule drugs, with oral options available for convenient dosing.
The modality landscape suggests an opportunity to explore alternative modalities like antibodies or peptides.
Nrf2 Clinical Trials 82 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Nrf2. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 25 | 21 | 3 | 1 | 88% |
| Phase 2 | 19 | 11 | 3 | 5 | 79% |
| Phase 3 | 20 | 10 | 5 | 5 | 67% |
| Phase 4 | 18 | 11 | 6 | 1 | 65% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
1 Phase 3 trial testing approved Nrf2 drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting Nrf2. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Nrf2 Drug Approval Timeline (2013 - 2025)
The first Nrf2-targeting drug was approved in 2013, with the most recent in 2025.
The approval timeline shows continued interest in Nrf2, but further investigation is needed to assess market saturation.
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Competitive Landscape
- • 3 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: 28 (7 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 Nrf2. A trial counts if an approved drug acting on Nrf2 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.