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Estriol

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Also known as 16.alpha.,17.beta.-estriol16.ALPHA.-HYDROXYESTRADIOLAacifemineColpogynEstriol acetate benzoateEstriol propionateEstriol succinateGynestIncurinNSC-12169OestriolOrtho-gynestOvestinSuccinate d'estriolSuccinato de estriolTrihydroxyestrinSID11532998SID144205873SID144211921

Summary

Estriol (CHEMBL193482) is an approved small-molecule estrogen (ATC G03CA04) targeting ESR1 and ESR2; indicated across 6 conditions including postmenopausal atrophic vaginitis and relapsing-remitting multiple sclerosis.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: G03CA04 (+1 more)
  • Targets: 2 (ESR1, ESR2)
  • Indications: 6 conditions
  • Clinical trials: 24
  • Chemistry: 288.4 Da · C18H24O3

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL193482
NameEstriol
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID5756
ChEBICHEBI:27974
ATCG03CA04, G03CC06
Molecular formulaC18H24O3
Molecular weight288.4
InChIKeyPROQIPRRNZUXQM-ZXXIGWHRSA-N

SMILES: C[C@]12CC[C@H]3[C@H]([C@@H]1C[C@H]([C@@H]2O)O)CCC4=C3C=CC(=C4)O

IUPAC name: (8R,9S,13S,14S,16R,17R)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,16,17-triol

ChEBI definition: A 3-hydroxy steroid that is estra-1,3,5(10)-trien-3-ol substituted by additional hydroxy groups at positions 16 and 17 (16α,17β-stereoisomer).

Pharmacological roles (ChEBI): estrogen.

Other ChEBI roles (chemical / environmental): human metabolite, human xenobiotic metabolite, mouse metabolite.

Also known as: 16.alpha.,17.beta.-estriol, 16.ALPHA.-HYDROXYESTRADIOL, Aacifemine, Colpogyn, Estriol, Estriol acetate benzoate, Estriol propionate, Estriol succinate, Gynest, Incurin, NSC-12169, Oestriol

Patent coverage: 6,652 distinct patent families (21,295 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 21,292 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
ESR1Estrogen receptor-αAgonist8.671.7%P03372
ESR2Estrogen receptor-βAgonist8.40.2%Q92731

Broader ChEMBL bioactivity targets: 15 (assay-derived). Sample: Solute carrier organic anion transporter family member 1A1, Androgen receptor, Glucocorticoid receptor, Estrogen receptor, Progesterone receptor, Prostaglandin G/H synthase 1, Sodium-dependent serotonin transporter, Sodium-dependent dopamine transporter, Estrogen receptor beta, Corticosteroid-binding globulin.

Bioactivity

ChEMBL activities: 12 potent at pChembl ≥ 5 of 20 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
ESR29.9EC500.13nMCHEMBL_ACT_13965789
ESR19.32Ki0.48nMCHEMBL_ACT_7654448
ESR18.77IC501.69nMCHEMBL_ACT_7654447
ESR18.7EC502nMCHEMBL_ACT_13965800
ESR18.26AC505.5nMCHEMBL_ACT_25138576
SHBG6.63Kd234.4nMCHEMBL_ACT_2155692
AR5.48AC503293nMCHEMBL_ACT_25203076
PGR5.48AC503305nMCHEMBL_ACT_25204009
SLC6A45.26Ki5491nMCHEMBL_ACT_7656582
P125305.06IC508635nMCHEMBL_ACT_7654487
P467205.01Ki9800nMCHEMBL_ACT_10996717
SERPINA65Ki10000nMCHEMBL_ACT_965576

Target pathways

Aggregated over 2 target gene(s): ESR1, ESR2.

Top Reactome pathways

17 total, by targets touching each:

PathwayTargetsGenes
PIP3 activates AKT signaling2ESR1, ESR2
Constitutive Signaling by Aberrant PI3K in Cancer2ESR1, ESR2
Nuclear Receptor transcription pathway2ESR1, ESR2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling2ESR1, ESR2
ESR-mediated signaling2ESR1, ESR2
Extra-nuclear estrogen signaling2ESR1, ESR2
Nuclear signaling by ERBB41ESR1
SUMOylation of intracellular receptors1ESR1
Ovarian tumor domain proteases1ESR1
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors1ESR1
RUNX1 regulates estrogen receptor mediated transcription1ESR1
RUNX1 regulates transcription of genes involved in WNT signaling1ESR1
Regulation of RUNX2 expression and activity1ESR1
Estrogen-dependent gene expression1ESR1
Mitochondrial unfolded protein response (UPRmt)1ESR1
Developmental Lineage of Mammary Gland Luminal Epithelial Cells1ESR1
Developmental Lineage of Mammary Gland Alveolar Cells1ESR1

Dominant GO biological processes

GO termTargets
negative regulation of transcription by RNA polymerase II2
regulation of DNA-templated transcription2
regulation of transcription by RNA polymerase II2
signal transduction2
estrogen receptor signaling pathway2
positive regulation of DNA-templated transcription2
positive regulation of transcription by RNA polymerase II2
obsolete positive regulation of DNA-binding transcription factor activity2
cellular response to estradiol stimulus2
cellular response to oxygen-containing compound2
antral ovarian follicle growth1
epithelial cell development1
chromatin remodeling1
phospholipase C-activating G protein-coupled receptor signaling pathway1
positive regulation of cytosolic calcium ion concentration1

Indications & clinical

Indications

6 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
postmenopausal atrophic vaginitis3MONDO:0001410EFO:1001271
relapsing-remitting multiple sclerosis2MONDO:0005314EFO:0003929
primary progressive multiple sclerosis2MONDO:0000451EFO:0008520
secondary progressive multiple sclerosis2MONDO:0000450EFO:0008522

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 24.

Phase distribution

PhaseTrials
PHASE27
PHASE16
Not specified5
PHASE33
PHASE42
PHASE2/PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02906111PHASE4UNKNOWNVaginal Estriol Before and Vaginal Surgery for Prolapse
NCT03032848PHASE4COMPLETEDVaginal Estrogens Comparative Trial on Pelvic Organ Prolapse Patients
NCT06391372PHASE3ACTIVE_NOT_RECRUITINGEffect of Local Estriol Treatment Before Vaginal Repair Surgery
NCT00816556PHASE3TERMINATEDA Trial to Evaluate the Efficacy of Low Dose Vaginal Estrogens in the Treatment of Atrophic Vaginitis
NCT03774407PHASE2/PHASE3COMPLETEDVaginal Estriol in Multiple Sclerosis
NCT04574999PHASE3COMPLETEDStudy to Determine Efficacy & Safety of a Low Concentration Estriol (0.005%) in Postmenopausal Vaginal Atrophy.
NCT00302731PHASE2TERMINATEDBioidentical ‘Natural’ Hormone Evaluation in Early Menopause
NCT00451204PHASE2COMPLETEDA Combination Trial of Copaxone Plus Estriol in Relapsing Remitting Multiple Sclerosis (RRMS)
NCT01408030PHASE2COMPLETEDNorth American Study of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
NCT01466114PHASE2UNKNOWNEstriol Treatment in Multiple Sclerosis (MS): Effect on Cognition
NCT02413008PHASE2COMPLETEDA Clinical Trial to Assess the Safety of 0.005 % Estriol Vaginal Gel in Hormone Receptor-Positive Postmenopausal Women With Early Stage Breast Cancer in Treatment With Aromatase Inhibitor in the Adjuvant Setting
NCT02967510PHASE2COMPLETEDStudy Evaluating the Efficacy and Safety of Three Formulations of Ultra-low Dose Estriol Vaginal Gel (0.005%, 0.002%, 0.0008% Estriol Vaginal Gel) for the Treatment of Vaginal Dryness in Postmenopausal Women With Vulvovaginal Atrophy
NCT04159493PHASE2WITHDRAWNA Randomized Controlled Phase 2 Study to Determine Lowest Efficacious Dose of Ovestin in Vulvar and Vaginal Atrophy
NCT00908570PHASE1COMPLETEDTopical Estriol for Vaginal Health
NCT01370551PHASE1COMPLETEDClinical Study of Vaginal Lactobacilli and Estriol (Gynoflor®) for Atrophic Vaginitis in Breast Cancer Patients
NCT02733731PHASE1UNKNOWNThe Treatment Effect of Chinese Herbal Compound Ointment on Atrophic Vaginitis
NCT03116022PHASE1COMPLETEDUse of Estriol at Distal Third of Vagina Improving Coital Pain in Post-menopause Women
NCT03343912PHASE1COMPLETEDEstriol and Trimegestone Dose-response Trial With Single Dose Application of Vaginal Rings
NCT03363997PHASE1COMPLETEDPharmacokinetics and Pharmacodynamics of 3 Dosages of Estriol After Continuous Vaginal Administration for 21 Days
NCT04045379Not specifiedACTIVE_NOT_RECRUITINGLASER and Radiofrequency and Genitourinary Syndrome of Menopause
NCT05335317Not specifiedRECRUITINGTreatment of Vaginal Atrophy With Low Intensity Nanosecond Neodymium Laser
NCT00156000Not specifiedWITHDRAWNfFN & E3 in the Prediction of PTB in Women With Twin Pregnancies Receiving 17OHP or Placebo
NCT01319968Not specifiedCOMPLETEDPostpartum Dyspareunia Resulting From Vaginal Atrophy
NCT04735549Not specifiedCOMPLETEDVulvovaginal Atrophy Correction Using Neodymium Laser

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

178 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
FULVESTRANTChEMBL + PubChemPhase 4 (approved)ESR1, ESR2
BAZEDOXIFENEChEMBLPhase 4 (approved)ESR1, ESR2
BITHIONOLChEMBLPhase 4 (approved)ESR1, ESR2
CISPLATINChEMBLPhase 4 (approved)ESR1, ESR2
DIETHYLSTILBESTROLChEMBLPhase 4 (approved)ESR1, ESR2
ELACESTRANTChEMBLPhase 4 (approved)ESR1, ESR2
ESTETROLChEMBLPhase 4 (approved)ESR1, ESR2
ESTRADIOLChEMBLPhase 4 (approved)ESR1, ESR2
ESTRONEChEMBLPhase 4 (approved)ESR1, ESR2
ETHINYL ESTRADIOLChEMBLPhase 4 (approved)ESR1, ESR2
HEXACHLOROPHENEChEMBLPhase 4 (approved)ESR1, ESR2
LASOFOXIFENEChEMBLPhase 4 (approved)ESR1, ESR2
MEDROXYPROGESTERONEChEMBLPhase 4 (approved)ESR1, ESR2
MIFEPRISTONEChEMBLPhase 4 (approved)ESR1, ESR2
PHENOLPHTHALEINChEMBLPhase 4 (approved)ESR1, ESR2
RALOXIFENEChEMBLPhase 4 (approved)ESR1, ESR2
SPIRONOLACTONEChEMBLPhase 4 (approved)ESR1, ESR2
TAMOXIFENChEMBLPhase 4 (approved)ESR1, ESR2
ACOLBIFENEChEMBLPhase 3ESR1, ESR2
AFIMOXIFENEChEMBLPhase 3ESR1, ESR2
AMCENESTRANTChEMBLPhase 3ESR1, ESR2
ARZOXIFENEChEMBLPhase 3ESR1, ESR2
BENSERAZIDEChEMBLPhase 3ESR1, ESR2
ALFATRADIOLChEMBLPhase 2ESR1, ESR2
AUS-131ChEMBLPhase 2ESR1, ESR2
BRILANESTRANTChEMBLPhase 2ESR1, ESR2
DAIDZEINChEMBLPhase 2ESR1, ESR2
ERTEBERELChEMBLPhase 2ESR1, ESR2
GENISTEINChEMBLPhase 2ESR1, ESR2
GTX-758ChEMBLPhase 2ESR1, ESR2
IDOXIFENEChEMBLPhase 2ESR1, ESR2
LEVORMELOXIFENEChEMBLPhase 2ESR1, ESR2
MOXESTROLChEMBLPhase 2ESR1, ESR2
PIPENDOXIFENEChEMBLPhase 2ESR1, ESR2
PRINABERELChEMBLPhase 2ESR1, ESR2
STALLIMYCINChEMBLPhase 2ESR1, ESR2
BosentanPubChemApprovedESR1, ESR2
DihydroergotaminePubChemApprovedESR1, ESR2
FidaxomicinPubChemApprovedESR1, ESR2
PropoxyphenePubChemApprovedESR1, ESR2
PyrazinamidePubChemApprovedESR1, ESR2
ACETOPHENAZINEChEMBLPhase 4 (approved)ESR1
ALECTINIBChEMBLPhase 4 (approved)ESR1
APOMORPHINEChEMBLPhase 4 (approved)ESR1
ARIPIPRAZOLEChEMBLPhase 4 (approved)ESR1
ASPIRINChEMBLPhase 4 (approved)ESR1
AZTREONAMChEMBLPhase 4 (approved)ESR1
BELINOSTATChEMBLPhase 4 (approved)ESR1
BENZBROMARONEChEMBLPhase 4 (approved)ESR1
BEXAROTENEChEMBLPhase 4 (approved)ESR1
BISACODYLChEMBLPhase 4 (approved)ESR1
BROMOCRIPTINEChEMBLPhase 4 (approved)ESR1
BUTOCONAZOLEChEMBLPhase 4 (approved)ESR1
CANDESARTAN CILEXETILChEMBLPhase 4 (approved)ESR1
CASPOFUNGINChEMBLPhase 4 (approved)ESR1
CEFADROXILChEMBLPhase 4 (approved)ESR1
CEFEPIMEChEMBLPhase 4 (approved)ESR1
CEFTAZIDIMEChEMBLPhase 4 (approved)ESR1
CERIVASTATINChEMBLPhase 4 (approved)ESR1
CHLOROTRIANISENEChEMBLPhase 4 (approved)ESR1

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot