ESTETROL ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H24O4
Molecular Weight	304.3808
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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=AJIPIJNNOJSSQC-NYLIRDPKSA-N

InChI=1S/C18H24O4/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/t12-,13-,14-,15-,16-,17+,18+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18464023 | https://www.ncbi.nlm.nih.gov/pubmed/26394847 | https://www.ncbi.nlm.nih.gov/pubmed/24997853 | http://adisinsight.springer.com/drugs/800044874

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor alpha 134 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18464023	Modulator 846		4.9 nM [Ki]
Estrogen receptor beta 113 Target ID: CHEMBL242 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18464023	Modulator 846		19.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Pregnancy 65 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27153745 https://www.ncbi.nlm.nih.gov/pubmed/26394847	Preventing	Phase III 665	Unknown Approved Use Unknown
Breast cancer 432 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24997853	Primary	Phase II 1147	Unknown Approved Use Unknown
Prostate cancer 186 Sources: https://clinicaltrials.gov/ct2/show/NCT02718378	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
17.9 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214154s000lbl.pdf	14.2 mg single, oral dose: 14.2 mg route of administration: Oral experiment type: SINGLE co-administered: DROSPIRENONE	DROSPIRENONE	ESTETROL plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
56.59 ng/mL EXPERIMENT https://doi.org/10.3390/ijms24119718	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28267365	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28267365	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

Value	Dose	Co-administered	Analyte	Population
59.1 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214154s000lbl.pdf	14.2 mg single, oral dose: 14.2 mg route of administration: Oral experiment type: SINGLE co-administered: DROSPIRENONE	DROSPIRENONE	ESTETROL plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
321.05 ng × h/mL EXPERIMENT https://doi.org/10.3390/ijms24119718	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 EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28267365	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
27 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214154s000lbl.pdf	14.2 mg single, oral dose: 14.2 mg route of administration: Oral experiment type: SINGLE co-administered: DROSPIRENONE	DROSPIRENONE	ESTETROL plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
26.64 h EXPERIMENT https://doi.org/10.3390/ijms24119718	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
52% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214154s000lbl.pdf	14.2 mg single, oral dose: 14.2 mg route of administration: Oral experiment type: SINGLE co-administered: DROSPIRENONE	DROSPIRENONE	ESTETROL plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg single, oral Highest studied dose Dose: 100 mg Route: oral Route: single Dose: 100 mg Sources: https://pubmed.ncbi.nlm.nih.gov/18464021	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/18464021	Sources: https://pubmed.ncbi.nlm.nih.gov/18464021
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: https://pubmed.ncbi.nlm.nih.gov/32379217	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/32379217	Disc. AE: uterine bleedin... AEs leading to discontinuation/dose reduction: uterine bleedin (grade 3, 2%) Sources: https://pubmed.ncbi.nlm.nih.gov/32379217
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: https://pubmed.ncbi.nlm.nih.gov/33242131	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/33242131	Sources: https://pubmed.ncbi.nlm.nih.gov/33242131

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/32379217	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/32379217

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P007XA8	https://www.1pchem.com/search?query=1P007XA8
Angene	AGN-PC-0WH1SZ	http://www.angenechemical.com/productshow/AGN-PC-0WH1SZ.html
Axon MedChem	1926	https://www.axonmedchem.com/product/1926
BOC Sciences	15183-37-6	http://www.bocsci.com/description.asp?cas=15183-37-6
Cayman Chemical	18232	http://www.caymanchem.com/app/template/Product.vm/catalog/18232
Chem Scene	CS-0008552	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0008552
eMolecules	31225888	https://orderbb.emolecules.com/search/#?query=31225888
MolPort	MolPort-042-665-780	https://www.molport.com/shop/molecule-link/MolPort-042-665-780
MolPort	MolPort-046-856-563	https://www.molport.com/shop/molecule-link/MolPort-046-856-563
Ryan Scientific	101-93964	https://ryansci.com/products?q=101-93964&list_q=&search_type=exact
Tetrahedron	TS75748	http://www.thsci.com/search.do?q=TS75748
Toronto Research Chemicals	E668450	https://www.trc-canada.com/product-detail/?CatNum=E668450

PubMed

Title	Date	PubMed
		252160577
Maternal and fetal estetrol levels during pregnancy.	2008	18464026
In vitro effects of estetrol on receptor binding, drug targets and human liver cell metabolism.	2008	18464025
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	18563397
Clinical applications for estetrol.	2009 Mar	19167495
Determination of endocrine disrupting compounds using temperature-dependent inclusion chromatography: I. Optimization of separation protocol.	2009 Oct 30	19362314
Determination of endocrine disrupting compounds using temperature-dependent inclusion chromatography: II. Fast screening of free steroids and related low-molecular-mass compounds fraction in the environmental samples derived from surface waters, treated and untreated sewage waters as well as activated sludge material.	2009 Oct 30	19356767
[Estrogen: estrone (E1), estradiol (E2), estriol (E3) and estetrol (E4)].	2010 Jul	20960812

Patents

Sample Use Guides

In Vivo Use Guide

15 mg administered once daily for 13 consecutive cycles following a 24/4-day regimen.

Route of Administration: Oral

In Vitro Use Guide

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.

Name

Type

Language

ESTETROL ANHYDROUS

Common Name

English

ESTETROL

Preferred Name

English

E4

Code

English

Estetrol [WHO-DD]

Common Name

English

ESTRA-1,3,5(10)-TRIENE-3,15,16,17-TETROL, (15.ALPHA.,16.ALPHA.,17.BETA.)-

Systematic Name

English

ESTETROL (ANHYDROUS) [USAN]

Common Name

English

ESTRA-1,3,5(10)-TRIENE-3,15.ALPHA.,16.ALPHA.,17.BETA.-TETROL

Systematic Name

English

estetrol [INN]

Common Name

English

ESTETROL (E4)

Common Name

English

E-4

Code

English

15.ALPHA.-HYDROXYESTRIOL

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

678119