Estrogen Receptor Modulators
30 drugsAbout Estrogen Receptor
The Estrogen Receptor (ER), encoded by the ESR1 gene, is a nuclear receptor that functions as a transcription factor. Activated by estrogen hormones, it regulates gene expression, impacting reproductive health, bone density, cardiovascular function, and brain activity.
Human genetic studies provide strong validation for ER as a therapeutic target, with variants linked to breast cancer (score 0.83) and estrogen resistance syndrome (score 0.76). Loss-of-function variants are associated with increased risk of estrogen resistance syndrome, supporting agonist-based therapies.
With 27 FDA-approved drugs, ER is exclusively targeted by small molecules, including CLIMARA and CONJUGATED ESTROGENS. Applications span oncology (8 drugs) and other therapeutic areas (19 drugs), with Bayer and Novartis among the top companies.
Estrogen Receptor Genetic Evidence Strong
Strong genetic evidence supports ESR1 as a drug target, with a maximum score of 0.83 for breast cancer.
The strong genetic support increases the probability of clinical success, especially for breast cancer indications.
💡 Why inhibition?
- • Loss-of-function variants reduce disease risk (OR < 1)
- • 33% directional consistency across 3 traits
- • Strong signal in integumentary system disease, reproductive system or breast disease, cancer or benign tumor pathways
Cross-Disease Effects
Trade-off: HighDirection of Effect
33% alignedEvidence Across Diseases
20 totalGWAS and other genetic studies link ESR1 to 44 diseases.
Activating this target may be therapeutic
Loss-of-function causes disease; activation may help
🔗 Colocalization Evidence 20 strong
max H4: 1.00eQTL/pQTL signals for ESR1 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 Estrogen Receptor Drugs
Twenty-three companies have approved drugs targeting the Estrogen Receptor, with Bayer and Novartis leading.
The fragmented competitive landscape suggests relatively low barriers to entry for new players.
| Drug | Company | Approved | Indications |
|---|---|---|---|
| VIVELLE-DOT | Novartis | 1996 | 4 |
| ACTIVELLA | Novo Nordisk | 1998 | 3 |
| ESTRADIOL AND NORETHINDRONE ACETATE | NOVAST LABS | 2008 | 3 |
| OSPHENA | DUCHESNAY | 2013 | 3 |
| PREMPRO | Pfizer | 1995 | 3 |
| SOLTAMOX | MAYNE PHARMA COMMRCL | 2005 | 3 |
| MYFEMBREE | SUMITOMO PHARMA AM | 2021 | 3 |
| RALOXIFENE HYDROCHLORIDE | SCIEGEN PHARMS | 2014 | 2 |
| FEMRING | MILLICENT MFG PR | 2003 | 2 |
| FYAVOLV | Lupin | 2015 | 2 |
| ANGELIQ | Bayer | 2005 | 2 |
| DUAVEE | Pfizer | 2013 | 2 |
| IMVEXXY | MAYNE PHARMA | 2018 | 2 |
| EVISTA | Eli Lilly | 1997 | 2 |
| CLIMARA PRO | BERLEX LABS | 2003 | 2 |
| ESTROGEL | ASCEND THERAPS US | 2004 | 2 |
| MINIVELLE | NOVEN | 2012 | 2 |
| FULVESTRANT | SAGENT PHARMS INC | 2019 | 1 |
| BIJUVA | MAYNE PHARMA | 2018 | 1 |
| MENOSTAR | Bayer | 1994 | 1 |
| TOREMIFENE CITRATE | MSN | 2018 | 1 |
| FASLODEX | AstraZeneca | 2002 | 1 |
| EVAMIST | PADAGIS US | 2007 | 1 |
| ORSERDU | STEMLINE THERAP | 2023 | 1 |
| DIVIGEL | VERTICAL PHARMS | 2007 | 1 |
| INLURIYO | Eli Lilly | 2025 | 1 |
| ELESTRIN | Viatris | 2006 | 1 |
Estrogen Receptor Drug Modality Landscape
Modalities
Routes of Administration
Estrogen Receptor is amenable to small molecule drugs, with oral options available for convenient dosing.
Exploring alternative modalities like antibodies or fusion proteins could offer a competitive advantage.
Estrogen Receptor Clinical Trials 853 trials
Phase 1-4 trials started in 2008 or later that test an FDA-approved drug acting on Estrogen Receptor. Source: ClinicalTrials.gov. How we count
Completion by Phase
| Phase | Total | Completed | Stopped | Active | Completion |
|---|---|---|---|---|---|
| Phase 1 | 262 | 132 | 41 | 88 | 76% |
| Phase 2 | 306 | 118 | 58 | 129 | 67% |
| Phase 3 | 159 | 73 | 16 | 69 | 82% |
| Phase 4 | 126 | 81 | 18 | 27 | 82% |
Top Sponsors
By Modality
Top Conditions
Top Drugs
Phase 3 Readout Calendar Pro
8 Phase 3 trials testing approved Estrogen Receptor drugs across all sponsors.
Coverage: trials whose intervention is an approved drug targeting Estrogen Receptor. Pre-approval candidates with development codes (e.g. AZD0901, MK-7240) are not yet linked. Anchored on CT.gov primary completion date.
Estrogen Receptor Drug Approval Timeline (1994 - 2025)
The first drug was approved in 1994 (CLIMARA), and the most recent in 2025 (CONJUGATED ESTROGENS), spanning 32 years.
The continued approval of new drugs indicates sustained interest and potential for further innovation in this area.
Pro Intelligence Preview
Deep insights for drug target analysis
Competitive Landscape
- • 23 companies competing
- • Market share by company
Full Drug Portfolio
- • All 30 approved drugs
- • Approval dates & indications
Genetic Validation
- • Full genetic evidence table
- • Effect sizes & directions
Approval Timeline
- • Full 30-drug timeline
- • First-of-modality markers
Clinical Trials Analysis
- • Sponsors: 416 (151 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 Estrogen Receptor. A trial counts if an approved drug acting on Estrogen 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.