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Details

Stereochemistry ABSOLUTE
Molecular Formula C18H24O4.H2O
Molecular Weight 322.396
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ESTETROL MONOHYDRATE

SMILES

O.C[C@]12CC[C@H]3[C@@H](CCC4=CC(O)=CC=C34)[C@@H]1[C@@H](O)[C@@H](O)[C@@H]2O

InChI

InChIKey=XRJNAPXFAXBPAM-BVTDNVAGSA-N
InChI=1S/C18H24O4.H2O/c1-18-7-6-12-11-5-3-10(19)8-9(11)2-4-13(12)14(18)15(20)16(21)17(18)22;/h3,5,8,12-17,19-22H,2,4,6-7H2,1H3;1H2/t12-,13-,14-,15-,16-,17+,18+;/m1./s1

HIDE SMILES / InChI

Molecular Formula C18H24O4
Molecular Weight 304.3808
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 7 / 7
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Estetrol is the natural human fetal selective estrogen receptor modulator. It is synthesized exclusively by the human fetal liver during pregnancy. Estetrol has a moderate affinity for human estrogen A receptor (ERa) and estrogen B receptor (ERb). Estetrol may be suitable as a potential drug for human use in applications such as hormone replacement therapy (vaginal atrophy, hot flushes), contraception and osteoporosis. The most common drug-related adverse events were lower abdominal pain, nausea, headache, dysmenorrhoea, breast enlargement and acne. Estetrol had been in clinical trials for the treatment of breast and prostate cancers.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
4.9 nM [Ki]
19.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
17.9 ng/mL
14.2 mg single, oral
dose: 14.2 mg
route of administration: Oral
experiment type: SINGLE
co-administered: DROSPIRENONE
ESTETROL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
56.59 ng/mL
45 mg single, oral
dose: 45 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTETROL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
8.01 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTETROL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
87.3 ng/mL
40 mg 1 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ESTETROL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
59.1 ng × h/mL
14.2 mg single, oral
dose: 14.2 mg
route of administration: Oral
experiment type: SINGLE
co-administered: DROSPIRENONE
ESTETROL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
321.05 ng × h/mL
45 mg single, oral
dose: 45 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTETROL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
194.2 ng × h/mL
40 mg 1 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ESTETROL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
27 h
14.2 mg single, oral
dose: 14.2 mg
route of administration: Oral
experiment type: SINGLE
co-administered: DROSPIRENONE
ESTETROL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
26.64 h
45 mg single, oral
dose: 45 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTETROL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
52%
14.2 mg single, oral
dose: 14.2 mg
route of administration: Oral
experiment type: SINGLE
co-administered: DROSPIRENONE
ESTETROL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg single, oral
Highest studied dose
Dose: 100 mg
Route: oral
Route: single
Dose: 100 mg
Sources:
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
15 mg 1 times / day multiple, oral
Minumum effective dose
Dose: 15 mg, 1 times / day
Route: oral
Route: multiple
Dose: 15 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
Disc. AE: uterine bleedin...
AEs leading to
discontinuation/dose reduction:
uterine bleedin (grade 3, 2%)
Sources:
60 mg 1 times / day multiple, oral
Studied dose
Dose: 60 mg, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
AEs

AEs

AESignificanceDosePopulation
uterine bleedin grade 3, 2%
Disc. AE
15 mg 1 times / day multiple, oral
Minumum effective dose
Dose: 15 mg, 1 times / day
Route: oral
Route: multiple
Dose: 15 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
PubMed

PubMed

TitleDatePubMed
Interaction of native alpha-cyclodextrin, beta-cyclodextrin and gamma-cyclodextrin and their hydroxypropyl derivatives with selected organic low molecular mass compounds at elevated and subambient temperature under RP-HPLC conditions.
2008 Aug
Clinical applications for estetrol.
2009 Mar
[Estrogen: estrone (E1), estradiol (E2), estriol (E3) and estetrol (E4)].
2010 Jul
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: in combination with 3 mg drospirenone tablets
15 mg administered once daily for 13 consecutive cycles following a 24/4-day regimen.
Route of Administration: Oral
Binding of Estetrol at the glucocorticoid, progesterone and testosterone receptors was only 11–15% at a concentration of 10 uM/l. Estetrol at a high concentration of 10 uM/l did not inhibit the major cytochrome P450 enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4.
Substance Class Chemical
Created
by admin
on Wed Apr 02 04:22:38 GMT 2025
Edited
by admin
on Wed Apr 02 04:22:38 GMT 2025
Record UNII
KC3GI9UM9V
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ESTETROL MONOHYDRATE
Official Name English
NEXTSTELLIS COMPONENT ESTETROL
Preferred Name English
E4 monohydrate
Common Name English
Estetrol monohydrate [WHO-DD]
Common Name English
ESTETROL [ORANGE BOOK]
Common Name English
ESTETROL (HYDROUS) [USAN]
Common Name English
ESTETROL HYDRATE
Common Name English
ESTRA-1,3,5(10)-TRIENE-3,15,16,17-TETROL, HYDRATE (1:1), (15.ALPHA.,16.ALPHA.,17.BETA.)-
Systematic Name English
ESTRA-1,3,5(10)-TRIENE-3,15.ALPHA.,16.ALPHA.,17.BETA.-TETROL MONOHYDRATE
Systematic Name English
ESTETROL HYDRATE [JAN]
Common Name English
Code System Code Type Description
SMS_ID
300000014640
Created by admin on Wed Apr 02 04:22:38 GMT 2025 , Edited by admin on Wed Apr 02 04:22:38 GMT 2025
PRIMARY
PUBCHEM
135391051
Created by admin on Wed Apr 02 04:22:38 GMT 2025 , Edited by admin on Wed Apr 02 04:22:38 GMT 2025
PRIMARY
CAS
2055649-81-3
Created by admin on Wed Apr 02 04:22:38 GMT 2025 , Edited by admin on Wed Apr 02 04:22:38 GMT 2025
PRIMARY
FDA UNII
KC3GI9UM9V
Created by admin on Wed Apr 02 04:22:38 GMT 2025 , Edited by admin on Wed Apr 02 04:22:38 GMT 2025
PRIMARY
RXCUI
2539035
Created by admin on Wed Apr 02 04:22:38 GMT 2025 , Edited by admin on Wed Apr 02 04:22:38 GMT 2025
PRIMARY
DAILYMED
KC3GI9UM9V
Created by admin on Wed Apr 02 04:22:38 GMT 2025 , Edited by admin on Wed Apr 02 04:22:38 GMT 2025
PRIMARY
NCI_THESAURUS
C169963
Created by admin on Wed Apr 02 04:22:38 GMT 2025 , Edited by admin on Wed Apr 02 04:22:38 GMT 2025
PRIMARY
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