Glucocorticoid receptor Modulators
41 drugsAbout Glucocorticoid receptor
The Glucocorticoid Receptor (GR), also known as NR3C1, is a ligand-activated transcription factor in the nuclear receptor superfamily. Upon activation by glucocorticoids like cortisol, GR regulates gene expression by binding to DNA, influencing immune responses, metabolism, and inflammation.
Human genetic studies provide strong validation for GR as a therapeutic target (score 0.92). Loss-of-function variants are associated with glucocorticoid resistance (score 0.92), while gain-of-function variants protect against atrial fibrillation (score 0.84), suggesting activation may be beneficial.
GR is targeted by 41 FDA-approved small molecule drugs, including MIFEPRISTONE, MIFEPREX and KORLYM. These drugs are used across respiratory conditions (15 drugs), rare diseases (5 drugs), and other therapeutic areas.
Glucocorticoid receptor Genetic Evidence Strong
Genetic evidence strongly supports GR as a drug target, with a maximum score of 0.92.
Strong genetic support suggests GR-targeting drugs have a higher probability of clinical success.
💡 Why activation?
- • Gain-of-function variants reduce disease risk — enhancing activity may help
- • 67% directional consistency across 3 traits
- • Strong signal in endocrine system disease, nutritional or metabolic disease, genetic, familial or congenital disease pathways
Cross-Disease Effects
Trade-off: HighDirection of Effect
67% alignedEvidence Across Diseases
6 totalGWAS and other genetic studies link NR3C1 to 6 diseases.
Loss-of-function causes disease; activation may help
Activating this target may be therapeutic
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for NR3C1 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 Glucocorticoid receptor Drugs
Twenty-eight companies have approved GR-targeting drugs, with Teva, UPSHER SMITH LABS, and ETON leading.
The fragmented competitive landscape suggests relatively low barriers to entry for new players.
Glucocorticoid receptor Drug Modality Landscape
Modalities
Routes of Administration
Glucocorticoid receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
The absence of other modalities like antibodies or biologics represents a whitespace opportunity.
Glucocorticoid receptor Clinical Trials 1,326 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Glucocorticoid receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 219 | 169 | 27 | 23 | 86% |
| Phase 2 | 342 | 220 | 56 | 66 | 80% |
| Phase 3 | 378 | 296 | 41 | 40 | 88% |
| Phase 4 | 387 | 246 | 65 | 76 | 79% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
5 Phase 3 trials testing approved Glucocorticoid receptor drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting Glucocorticoid receptor. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Glucocorticoid receptor Drug Approval Timeline (1998 - 2025)
Seasonal Allergic Rhinitis
The first GR-targeting drug was approved in 1998, with the most recent approval in 2025.
The continued approval of new drugs indicates sustained interest and potential for further innovation.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 26 companies competing
- • Market share by company
Full Drug Portfolio
- • All 41 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 41-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 566 (146 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 Glucocorticoid receptor. A trial counts if an approved drug acting on Glucocorticoid receptor 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.