Protein / target

Estrogen receptor beta

ESR2Q92731Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
20
Approved medicines
24
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Nuclear estrogen receptor activity

Primary system

Endocrine & metabolic

Strongest disease association

breast cancer

Literature evidence · score 0.62

Therapeutic maturity

Clinically validated target

20 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

20 approved · 14 in clinical development

24 linked trials

Research activity

Emerging research

3 papers · latest 2020

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560)

Subcellular location

Nucleus
Domains and Gene Ontology detail (27)

Domains & features

NR LBD

Gene Ontology

  • Cchromatin
  • Cmitochondrion
  • Cnucleoplasm
  • Cnucleus
  • FDNA binding
  • FDNA-binding transcription factor activity, RNA polymerase II-specific
  • Fenzyme binding
  • Festrogen response element binding
  • Fnuclear estrogen receptor activity
  • Fnuclear receptor activity
  • Fnuclear steroid receptor activity
  • Freceptor antagonist activity

530 aa · 59 kDa · 9 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Transcriptional regulationGO · ReactomeNuclear receptor signallingGO · Reactome
View supporting evidence

Transcriptional regulation

  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·RNA polymerase II cis-regulatory region sequence-specific DNA binding
  • ·DNA-templated transcription
  • ·negative regulation of transcription by RNA polymerase II

Nuclear receptor signalling

  • ·DNA-binding transcription factor activity, RNA polymerase II-specific
  • ·nuclear receptor activity
  • ·Nuclear Receptor transcription pathway
View underlying pathways (6)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

NCOA1ESR1NCOA3SRCNCOA2SP1MED1CAV1NCOR1JUNESR2

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

3

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

equol
Narrow target profileAgonist

Estrogen receptor beta agonist

Direct interaction with this protein · Only this protein recorded as a target

Lasofoxifene
ApprovedModulator

Estrogen receptor modulator

Appears in clinical studies involving osteoporosis, breast cancer, viral infectious disease

Acts on a complex — shared with ESR1 · 1 of 2 recorded protein targets — narrow recorded profile

Ospemifene
ApprovedModulator

Estrogen receptor modulator

Appears in clinical studies involving menopause, Dyspareunia, Atrophy, postmenopausal atrophic vaginitis

Acts on a complex — shared with ESR1 · 1 of 2 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

osteoporosis0.97

Clinical · overall 0.61

breast cancer0.97

Clinical · overall 0.62

postmenopausal osteoporosis0.95

Clinical · overall 0.58

menopause0.93

Clinical · overall 0.57

Dyspareunia0.92

Clinical · overall 0.56

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

Atrophy0.55

Clinical

neoplasm0.49

Literature

breast carcinoma0.49

Literature

primary ovarian failure0.48

Clinical

hypogonadism0.47

Clinical

Show all associations
breast cancer0.62
osteoporosis0.61
postmenopausal osteoporosis0.58
menopause0.57
Dyspareunia0.56
Atrophy0.55
neoplasm0.49
breast carcinoma0.49
primary ovarian failure0.48
hypogonadism0.47

Open Targets ranks 2,715 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 35 total

LASOFOXIFENE TARTRATEApproval

postmenopausal osteoporosis

OSPEMIFENEApproval

menopause · Dyspareunia · Atrophy

ERTEBERELPhase 2

benign prostatic hyperplasia · schizophrenia · Cognitive impairment

ESTRIOLApproval

Atrophic Vaginitis · Atrophic Vaginitis · urgency urinary incontinence

DROLOXIFENEPhase 2

breast cancer

ACOLBIFENEPhase 3

breast cancer

ESTRAMUSTINE PHOSPHATE SODIUMApproval

carcinoma · prostate adenocarcinoma · prostate cancer

AFIMOXIFENEPhase 2

breast cancer · breast ductal adenocarcinoma · ductal breast carcinoma in situ

PRINABERELPhase 2

inflammatory bowel disease · endometriosis · rheumatoid arthritis

IDOXIFENEPhase 3

breast cancer

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · Small Molecule BinderOC · Approved Drug

Safety liabilities

regulation of transcription factor activityprotein stabilizationregulation of steroid biosynthetic processbone density lossregulation of steroid hormone biosynthetic processtamoxifen-induced increase in triglycerides

Clinical trials

24

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Show remaining trials (18)

COMPLETED · via Lasofoxifene · NCT00141323

ClinicalTrials.gov via the drug-target graph.

Research activity

3 papers · to 2020

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Li LC · Bioinformatics (Oxford, England) · 2002

Wang Y · Annual review of pathology · 2020

Recent

The Origin and Pathogenesis of Endometriosis.

Wang Y · Annual review of pathology · 2020

MethPrimer: designing primers for methylation PCRs.

Li LC · Bioinformatics (Oxford, England) · 2002

Europe PMC papers linked directly to this protein.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

breast cancerWell supported
0.77
agreement 0.610.92
Clinical83%Literature17%

Open Targets aggregate 0.62 · 2 independent evidence families

osteoporosisWell supported
0.75
agreement 0.600.91
Clinical90%Literature10%

Open Targets aggregate 0.61 · 2 independent evidence families

postmenopausal osteoporosisModerately supported
0.72
agreement 0.560.87
Clinical97%Literature3%

Open Targets aggregate 0.58 · 2 independent evidence families

menopauseModerately supported
0.70
agreement 0.550.86
Clinical98%Literature2%

Open Targets aggregate 0.57 · 2 independent evidence families

DyspareuniaModerately supported
0.69
agreement 0.530.84
Clinical100%Literature0%

Open Targets aggregate 0.56 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

24

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. Label change2025-02-07

    Label change: OSPEMIFENE (NDA203505)

    fda · regulatory · fda · via Ospemifene

  2. New publication2024-09-10
    Hormonal Treatments and Vaginal Moisturizers for Genitourinary Syndrome of Menopause : A Systematic Review.

    Annals of internal medicine · 2024 · 14 citations · Europe PMC · via Ospemifene

  3. Label change2024-02-15

    Label change: OSPEMIFENE (NDA203505)

    fda · regulatory · fda · via Ospemifene

  4. New publication2024-02-11
    From Gut to Hormones: Unraveling the Role of Gut Microbiota in (Phyto)Estrogen Modulation in Health and Disease.

    Molecular nutrition & food research · 2024 · 50 citations · Europe PMC · via equol

  5. New publication2023-12-01
    Lasofoxifene versus fulvestrant for ER+/HER2- metastatic breast cancer with an ESR1 mutation: results from the randomized, phase II ELAINE 1 trial.

    Annals of oncology : official journal of the European Society for Medical Oncology · 2023 · 33 citations · Europe PMC · via Lasofoxifene

  6. New publication2023-12-01
    Open-label, phase II, multicenter study of lasofoxifene plus abemaciclib for treating women with metastatic ER+/HER2- breast cancer and an ESR1 mutation after disease progression on prior therapies: ELAINE 2.

    Annals of oncology : official journal of the European Society for Medical Oncology · 2023 · 37 citations · Europe PMC · via Lasofoxifene

  7. New publication2019-09-16
    Equol: A Bacterial Metabolite from The Daidzein Isoflavone and Its Presumed Beneficial Health Effects.

    Nutrients · 2019 · 245 citations · Europe PMC · via equol

  8. Indication expanded2019-01-25

    Indication expansion: OSPEMIFENE (NDA203505)

    fda · regulatory · fda · via Ospemifene

  9. Label change2018-10-26

    Label change: OSPEMIFENE (NDA203505)

    fda · regulatory · fda · via Ospemifene

  10. New publication2018-04-18
    Improvements to the Vulva, Vestibule, Urethral Meatus, and Vagina in Women Treated With Ospemifene for Moderate to Severe Dyspareunia: A Prospective Vulvoscopic Pilot Study.

    Sexual medicine · 2018 · 22 citations · Europe PMC · via Ospemifene

  11. Supplemental approval2017-03-17

    Supplemental approval: OSPEMIFENE (NDA203505)

    fda · regulatory · fda · via Ospemifene

  12. Supplemental approval2016-11-03

    Supplemental approval: OSPEMIFENE (NDA203505)

    fda · regulatory · fda · via Ospemifene

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.