ESR1 estrogen receptor 1
ENSG00000091831 · protein coding · Open Targets profile
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE- independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa- B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity). {ECO:0000250|UniProtKB:P06211, ECO:0000269|PubMed:10681512, ECO:0000269|PubMed:10816575, ECO:0000269|PubMed:11477071, ECO:0000269|PubMed:11682626, ECO:0000269|PubMed:14764652, ECO:0000269|PubMed:15078875, ECO:0000269|PubMed:15891768, ECO:0000269|PubMed:16043358, ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:16684779, ECO:0000269|PubMed:17922032, ECO:0000269|PubMed:17932106, ECO:0000269|PubMed:18247370, ECO:0000269|PubMed:19350539, ECO:0000269|PubMed:20074560, ECO:0000269|PubMed:20705611, ECO:0000269|PubMed:21330404, ECO:0000269|PubMed:22083956, ECO:0000269|PubMed:37478846, ECO:0000269|PubMed:7651415, ECO:0000269|PubMed:9328340}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt loc med conf
- PROTAC
- Advanced Clinical, Literature, UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.2275799959897995 (upper bound 0.36871999502182007). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against ESR1 (mestranol, estradiol, estrogens, esterified, estradiol cypionate, quinestrol, estrone, estropipate, bazedoxifene, elacestrant, diethylstilbestrol, polyestradiol, estrogens, conjugated synthetic a), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Mary ChamberlinDartmouth-Hitchcock Medical Center · 2 of 3 trials Phase 2+
- Antonio Llombart-CussacArnau de Vilanova Hospital, Valencia, Spain · 2 of 2 trials Phase 2+
- Elizabeth AndersenUniversity of North Carolina, Chapel Hill · 2 of 2 trials Phase 2+
- Fabrice ANDREGustave Roussy, Cancer Campus, Grand Paris · 2 of 2 trials Phase 2+Ph2NCT05625087 · Detection of Tumor DNA in the Blood of Patients Receiving Standard Therapy for Hormone Receptor-positive (HR+) Non-HER2 Expressing (HER2-) Metastatic Breast Cancer as a Tool to Select Those Who May Benefit From the Next Course of Fulvestrant in Combination With Alpelisib or Ribociclibbrief
- Javier CortésIOB Institute of Oncology, Quironsalud Group, Madrid & Barcelona, Spain · 2 of 2 trials Phase 2+
- Kristina FanucciDana-Farber Cancer Institute · 2 of 2 trials Phase 2+
- Polly NiravathThe Methodist Hospital Research Institute · 2 of 2 trials Phase 2+
- Sherry ShenMemorial Sloan Kettering Cancer Center · 2 of 2 trials Phase 2+
- Stephen ChiaBCCA - Vancouver Cancer Centre · 2 of 2 trials Phase 2+
- Tufia C. HaddadMayo Clinic in Rochester · 2 of 2 trials Phase 2+
- A E van Leeuwen-StokBOOG Study Center · 1 of 1 trials Phase 2+
- A. JagerBorstkanker Onderzoek Groep · 1 of 1 trials Phase 2+
- Aaron M LazorwitzYale University · 1 of 1 trials Phase 2+
- Adrienne G WaksDana-Farber Cancer Institute · 1 of 1 trials Phase 2+
- Ahmed s SaadProfessor of OB & GYN · 1 of 1 trials Phase 2+
Registry trials of mestranol, estradiol, estrogens, esterified, estradiol cypionate, quinestrol, estrone, estropipate, bazedoxifene, elacestrant, diethylstilbestrol, polyestradiol, estrogens, conjugated synthetic a updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 272 of 377 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 23 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
235 trials of drugs against ESR1 were stopped early; 23 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of mestranol, estradiol, estrogens, esterified, estradiol cypionate, quinestrol, estrone, estropipate, bazedoxifene, elacestrant, diethylstilbestrol, polyestradiol, estrogens, conjugated synthetic a, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 235.
- terminated · 2026-10-15 · Spanish Breast Cancer Research Group · matched by the registry's drug synonyms“Study prematurely terminated due to recruitment challenges, low incidence of the target population, evolving treatment landscape, ethical considerations, and inability to ensure funding through study completion.”
- terminated · 2026-10-14 · UNICANCER · matched by the registry's drug synonyms“poor accrual”
- terminated · 2026-10-06 · Boehringer Ingelheim · matched by the registry's drug synonyms“Sponsor decision - hold following the evaluation of a safety event. No current sites in the US.”
- terminated · 2026-09-24 · Tvardi Therapeutics, Incorporated · matched by the registry's drug synonyms“The study was terminated prior to Phase 2 due to slow accrual.”
- terminated · 2026-08-19 · Boundless Bio, Inc. · matched by the registry's drug synonyms“The study was terminated primarily due to a business decision related to a corporate transaction and was not driven by any safety signal.”
- terminated · 2026-07-21 · Context Therapeutics Inc. · Elacestrant“Sponsor decision to discontinue onapristone development.”
- terminated · 2026-07-10 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Novartis terminated the trial early because the collected data were sufficient to perform the analysis stated for the primary endpoint.”
- suspended · 2026-06-25 · ART Fertility Clinics LLC · Estradiol Valerate 2 MG“Difficulty of enrolling and recruiting patients”
- terminated · 2026-06-25 · SOLTI Breast Cancer Research Group · matched by the registry's drug synonyms“The study was prematurely halted because enrollment was significantly delayed compared with the original projections due to the evolving therapeutic landscape.”
- withdrawn · 2026-06-22 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Business decision”
- withdrawn · 2026-06-05 · University of Chicago · matched by the registry's drug synonyms“Data not collected and analyzed; withdrawn due to lack of bandwidth.”
- terminated · 2026-05-14 · EQRx, Inc. · matched by the registry's drug synonyms“The study is being closed based on corporate changes at EQRx and is not related to any efficacy or safety issues with lerociclib.”
- terminated · 2026-04-08 · National Institute of Allergy and Infectious Diseases (NIAID) · Estradiol“Trial terminated by Sponsor.”
- terminated · 2026-04-01 · Jocelyn Fitzgerald · matched by the registry's drug synonyms“unable to reach the recruitment numbers required to power our primary outcome”
- terminated · 2026-03-31 · Criterium, Inc. · Elacestrant“Study was terminated due to delayed recruitment.”
- terminated · 2026-03-03 · National Cancer Institute (NCI) · matched by the registry's drug synonyms“Other - slow accrual”
- terminated · 2026-02-24 · Sanofi · matched by the registry's drug synonyms“Sponsor decision to prematurely stop the study, not linked to any safety concern.”
- withdrawn · 2026-02-23 · University of Virginia · matched by the registry's drug synonyms“No funding, time, or personnel to complete this study.”
- terminated · 2026-02-18 · University of Alabama at Birmingham · Estradiol 0.01% Vag Cream“Ran out of funding”
- terminated · 2026-01-22 · Dana-Farber Cancer Institute · matched by the registry's drug synonyms“Slow accrual”
- terminated · 2026-01-09 · M.D. Anderson Cancer Center · matched by the registry's drug synonyms“Copanlisib development was discontinued by Bayer following withdrawal of copanlisib in relapsed follicular lymphoma in November 2023.”
- terminated · 2026-01-05 · M.D. Anderson Cancer Center · matched by the registry's drug synonyms“<75% Participation”
- terminated · 2025-11-28 · Blueprint Medicines Corporation · matched by the registry's drug synonyms“This trial was terminated prior to the initiation of Phase 2 for reasons not due to safety concerns.”
- terminated · 2025-11-21 · Organon and Co · matched by the registry's drug synonyms“Sponsor decision to stop the study early and complete all required study close-out activities. This decision was made for business reasons unrelated to safety. None of the pre-specified efficacy endpoints were analyzed.”
- terminated · 2025-11-13 · Taiho Oncology, Inc. · matched by the registry's drug synonyms“The Sponsor decided to discontinue the study due to strategic considerations and not due to any safety-related concerns.”
Paediatric incentives and obligations for ESR1's drugs
For mestranol, estradiol, estrogens, esterified, estradiol cypionate, quinestrol, estrone, estropipate, bazedoxifene, elacestrant, diethylstilbestrol, polyestradiol, estrogens, conjugated synthetic a: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · ESR1 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-002428-PIP02-18 (relugolix;estradiol;norethisterone acetate, Treatment of endometriosis): RP: decision refers to a refusal on a proposed Paediatric Investigation Plan, 16 Aug 2019; EMEA-002428-PIP01-18 (relugolix;estradiol;norethisterone acetate, Treatment of leiomyoma of uterus): W: decision granting a waiver in all age groups for all conditions or indications, 22 Mar 2019; EMEA-000998-PIP01-10 (bazedoxifene;conjugated estrogens, Postmenopausal osteoporosis): W: decision granting a waiver in all age groups for all conditions or indications, 3 Sept 2010Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/14/1367 positive 19 Nov 2014: Treatment of hereditary haemorrhagic telangiectasiaRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA EU/3/14/1367, 2026-11-11
- Authorised in the EU: yes · Ryeqo: authorised since 16 Jul 2021; Orserdu: authorised since 15 Sept 2023; Duavive: authorised since 16 Dec 2014; Conbriza: authorised since 17 Apr 2009; +3 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of mestranol, estradiol, estrogens, esterified, estradiol cypionate, quinestrol, estrone, estropipate, bazedoxifene, elacestrant, diethylstilbestrol, polyestradiol, estrogens, conjugated synthetic aRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 179 interventional studies of mestranol, estradiol, estrogens, esterified, estradiol cypionate, quinestrol, estrone, estropipate, bazedoxifene, elacestrant, diethylstilbestrol, polyestradiol, estrogens, conjugated synthetic a include patients under 18; 22 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 51 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.