Estetrol Anhydrous

Summary

Estetrol Anhydrous (CHEMBL1230314) is an approved small-molecule estrogen receptor agonist; indicated across 3 conditions including vulvovaginitis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Indications: 3 conditions
• Clinical trials: 16
• Chemistry: 304.4 Da · C18H24O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1230314
Name	Estetrol Anhydrous
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	27125
ChEBI	CHEBI:142773
Molecular formula	C18H24O4
Molecular weight	304.4
InChIKey	AJIPIJNNOJSSQC-NYLIRDPKSA-N

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

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

ChEBI definition: A 3-hydroxy steroid that is 17β-estradiol which has been substituted at the 15α and 16α positions by two additional hydroxy groups. It is a natural estrogen produced exclusively during pregnancy by the fetal liver.

Pharmacological roles (ChEBI): estrogen, estrogen receptor agonist, oral contraceptive.

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

Also known as: 15.alpha.-hydroxyestriol, E-4, E4, Estetrol (anhydrous), Estetrol (e4), Estetrol anhydrous, ESTETROL ANHYDROUS, ESTETROL, estetrol

Parent form; salt/anhydrous children: CHEMBL6068423

Patent coverage: 312 distinct patent families (1,198 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,160 (97%) 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

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Estrogen receptor, Estrogen receptor beta.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
ESR1	8.31	Ki	4.9	nM	CHEMBL_ACT_16338992
ESR1	8.31	Ki	4.9	nM	CHEMBL_ACT_16355418
ESR1	8.31	Ki	4.9	nM	CHEMBL_ACT_26595848
ESR1	8.31	Ki	4.9	nM	CHEMBL_ACT_26596475
ESR1	8.31	Ki	4.9	nM	CHEMBL_ACT_26768812
ESR2	7.72	Ki	19	nM	CHEMBL_ACT_16288577
ESR2	7.72	Ki	19	nM	CHEMBL_ACT_16353954
ESR2	7.72	Ki	19	nM	CHEMBL_ACT_26595857
ESR2	7.72	Ki	19	nM	CHEMBL_ACT_26596484
ESR2	7.72	Ki	19	nM	CHEMBL_ACT_26768815

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

3 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).

Indication	Trial phase	MONDO	EFO
vulvovaginitis	1	MONDO:0007019	EFO:1001240

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

Clinical trials

Total trials: 16.

Phase distribution

Phase	Trials
PHASE1	5
PHASE2	4
PHASE4	3
PHASE3	2
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05837624	PHASE4	RECRUITING	Estetrol/Drospirenone to Reduce the Average Size of Endometriomas
NCT06316180	PHASE4	COMPLETED	The Use of Drospirenone/Estetrol in Random Start Rapid Endometrial Preparation
NCT06324851	PHASE4	COMPLETED	The Use of Drospirenone/Estetrol, Nomegestrol Acetate/Estradiol and Ethinylestradiol/Dienogest in Random Start Rapid Endometrial Preparation
NCT04090957	PHASE3	COMPLETED	Estetrol for the Treatment of Moderate to Severe Vasomotor Symptoms in Postmenopausal Women (E4Comfort II)
NCT04209543	PHASE3	COMPLETED	Estetrol for the Treatment of Moderate to Severe Vasomotor Symptoms in Postmenopausal Women (E4Comfort Study I)
NCT00464516	PHASE2	COMPLETED	Preoperative Estetrol in Breast Cancer
NCT00563472	PHASE2	COMPLETED	Feasibility Study Into the Contraceptive Effect of Estetrol
NCT02718144	PHASE1/PHASE2	COMPLETED	Assessment of Safety and Efficacy of Estetrol in Postmenopausal Women With Advanced Estrogen Receptor Positive (ER+) Breast Cancer
NCT02834312	PHASE2	COMPLETED	E4Relief (Response to Estetrol in Life Improvement for MEnopausal-associated Hot Flushes)
NCT03361969	PHASE2	COMPLETED	Evaluation of Effects of Estetrol on Testosterone Suppression and Quality of Life in Prostate Cancer Patients Treated With an LHRH Agonist.
NCT00163033	PHASE1	COMPLETED	Study to Evaluate 3 Dosages of Estetrol After 28 Days Administration in Healthy Postmenopausal Women
NCT02718378	PHASE1	COMPLETED	Evaluation of Safety and Efficacy of Estetrol in Healthy Men
NCT02720224	PHASE1	COMPLETED	Study Conducted to Further Understand the Elimination Pathways, Metabolite Profile and PK Profile of 14C-estetrol
NCT03798197	PHASE1	COMPLETED	Effect of Food on the Bioavailability of 30 mg Estetrol (E4) Tablet in Healthy Postmenopausal Female Volunteers
NCT04819906	PHASE1	COMPLETED	Effect of Estetrol Monohydrate (E4) on QTc Interval
NCT07061093	Not specified	RECRUITING	Prospective Evaluation on the Role Exerted by Hormonal Contraceptives on 24-h Blood Pressure. A Prospective Observational Study

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).