ESTRIOL SUCCINATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H32O9
Molecular Weight	488.5269
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12C[C@@H](OC(=O)CCC(O)=O)[C@H](OC(=O)CCC(O)=O)[C@@]1(C)CC[C@]3([H])C4=C(CC[C@@]23[H])C=C(O)C=C4

InChI

InChIKey=VBRVDDFOBZNCPF-BRSFZVHSSA-N

InChI=1S/C26H32O9/c1-26-11-10-17-16-5-3-15(27)12-14(16)2-4-18(17)19(26)13-20(34-23(32)8-6-21(28)29)25(26)35-24(33)9-7-22(30)31/h3,5,12,17-20,25,27H,2,4,6-11,13H2,1H3,(H,28,29)(H,30,31)/t17-,18-,19+,20-,25+,26+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/pro/estradiol.html
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT02906111 | https://www.ncbi.nlm.nih.gov/pubmed/27838536 | https://clinicaltrials.gov/ct2/show/NCT02419729 | https://www.ncbi.nlm.nih.gov/pubmed/26786399 |

Estriol (E3), also spelled oestriol, is a steroid, a weak agonist of the estrogen receptors ERα and ERβ., and a minor female sex hormone. According to in vitro study, the relative binding affinity (RBA) of estriol for the human ERα and ERβ was 11.3% and 17.6% of that estradiol, respectively, and the relative transactivational capacity of estrone at the ERα and ERβ was 10.6% and 16.6% of that of estradiol, respectively. Estriol is marketed widely in Europe and elsewhere throughout the world under the brand names Ovestin, Ortho-Gynest, and a variety of others. It is available in oral tablet, vaginal cream, and vaginal suppository form, and is used in menopausal hormone therapy for the treatment of menopausal symptoms. Estriol is also available in some countries as estriol succinate (brand name Synapause), a dosage-equivalent ester prodrug of estriol. Estriol and estriol succinate are not approved for use in the United States and Canada, although they have been produced and sold by compounding pharmacies in North America for use as a component of bioidentical hormone therapy. Estriol can be measured in maternal blood or urine and can be used as a marker of fetal health and well-being. If levels of unconjugated estriol (uE3 or free estriol) are abnormally low in a pregnant woman, this may indicate chromosomal or congenital anomalies like Down syndrome or Edward's syndrome. It is included as part of the triple test and quadruple test for antenatal screening for fetal anomalies.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Estrogen receptor 75 Target ID: CHEMBL2093866 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9357533	Agonist 2678
Testis-specific androgen-binding protein 6 Target ID: CHEMBL3305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18330978	Binding Agent 1064	234.42 nM [Kd]
Corticosteroid binding globulin 4 Target ID: CHEMBL2421 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15139751	Binding Agent 1064

Conditions

Condition	Modality	Highest Phase	Product
Genital prolapse 3 Sources: https://clinicaltrials.gov/ct2/show/NCT02906111	Primary	Phase IV 63	Ovestin Approved Use Unknown
Urinary tract infections 205 Sources: https://clinicaltrials.gov/ct2/show/NCT00900653	Primary	Phase IV 63	Ovestin Approved Use Unknown
Atrophic vaginitis 13 Sources: https://clinicaltrials.gov/ct2/show/NCT00816556	Primary	Phase III 656	Ovestin Approved Use Unknown

PubMed

Title	Date	PubMed
Plasma levels and excretion of estrogens in urine in chronic lever disease.	1975 Jul	1171044
[Hormone replacement therapy in women with arterial hypertension in peri- and postmenopause: hemodynamic effects].	2001	11763512
Multiple marker second trimester serum screening for pre-eclampsia.	2001	11480445
Determination of estradiol metabolites in human liver microsome by high performance liquid chromatography-electrochemistry detector.	2001 Apr	11742592
Preterm birth risk assessment.	2001 Aug	11561909
Second trimester maternal serum analytes in triploid pregnancies: correlation with phenotype and sex chromosome complement.	2001 Aug	11536271
Maternal serum screening for fetal trisomy 18: benefits of patient-specific risk protocol.	2001 Aug	11518881
Identification of 16alpha,19-dihydroxyandrostenedione in the serum of pregnant women by gas chromatography-mass spectrometry.	2001 Aug	11510491
Inhibition of large-conductance calcium-activated potassium channel by 2-methoxyestradiol in cultured vascular endothelial (HUV-EC-C) cells.	2001 Aug 1	11547343
Synthesis of ring B unsaturated estriols. Confirming the structure of a diagnostic analyte for Smith-Lemli-Opitz syndrome.	2001 Aug 9	11483057
Sequential first and second trimester screening tests: correlation of the markers' levels in normal versus Down syndrome affected pregnancies.	2001 Dec	11787048
Plasma prolactin/oestradiol ratio at 38 weeks gestation predicts the duration of lactational amenorrhoea.	2001 Dec	11726571
Unconventional estrogens: estriol, biest, and triest.	2001 Dec	11600867
Use of solid-phase extraction in various of its modalities for sample preparation in the determination of estrogens and progestogens in sediment and water.	2001 Dec 14	11771833
Removal of endocrine-disrupting chemicals in activated sludge treatment works.	2001 Dec 15	11775141
Treatment of bitches with acquired urinary incontinence with oestriol.	2001 Dec 22-29	11808663
An immunoassay for small analytes with theoretical detection limits.	2001 Jul 15	11476240
Maternal serum screening for Down's syndrome, open neural tube defects and trisomy 18.	2001 Jun	11506458
Sex hormones in experimental autoimmune encephalomyelitis: implications for multiple sclerosis.	2001 Jun	11499404
A placebo-controlled trial of long-term oral combined continuous hormone replacement therapy in postmenopausal women: effects on arterial compliance and endothelial function.	2001 Nov	11894980
Lens culinaris agglutinin-reactive alpha-fetoprotein, an alternative variant to alpha-fetoprotein in prenatal screening for Down's syndrome.	2001 Nov	11679535
Identification of negative and positive estrogen response elements in human GnRH upstream promoter in the placental JEG-3 cells.	2001 Nov 26	11694348
[Influence of hormonal replacement therapy on bacterial vaginosis in the group of peri- and postmenopausal women].	2001 Oct	11848019
ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical management guidelines for obstetrician-gynecologists. Number 31, October 2001. (Replaces Technical Bulletin number 206, June 1995; Committee Opinion number 172, May 1996; Committee Opinion number 187, September 1997; Committee Opinion number 198, February 1998; and Committee Opinion number 251, January 2001).	2001 Oct	11592272
[Health Council of Netherlands recommendation 'Serum screening for risk assessment of Down syndrome for all women' poorly supported].	2001 Oct 20	11695097
[Cross-over comparison of the pharmacokinetics of estradiol during hormone replacement therapy with estradiol valerate or micronized estradiol].	2001 Sep	11709743
Effects of 17-beta estradiol and estriol on NMDA-induced toxicity and apoptosis in primary cultures of rat cortical neurons.	2001 Sep	11596861
Enhancement of collagen-induced arthritis in female mice by estrogen receptor blockage.	2001 Sep	11592382
Inaccurate estimation of risk in second trimester serum screening for Down syndrome among women who have already had first trimester screening.	2001 Sep	11559910
Mammographic density changes during different postmenopausal hormone replacement therapies.	2001 Sep	11532462
Comparison of an array of in vitro assays for the assessment of the estrogenic potential of natural and synthetic estrogens, phytoestrogens and xenoestrogens.	2001 Sep 14	11518614
Short term oral estriol treatment restores normal premenopausal vaginal flora to elderly women.	2001 Sep 28	11574185
Accuracy of expected risk of Down syndrome using the second-trimester triple test.	2002	11901067
Estradiol valerate/dienogest.	2002	11827562
Kinetic comparison of tissue non-specific and placental human alkaline phosphatases expressed in baculovirus infected cells: application to screening for Down's syndrome.	2002	11818032
Use of low potency estrogens does not reduce the risk of hip fracture.	2002 Apr	11934654
Reduced 11beta-hydroxysteroid dehydrogenase type 2 activity is associated with decreased birth weight centile in pregnancies complicated by asthma.	2002 Apr	11932298
Steroid hormone levels during pregnancy and incidence of maternal breast cancer.	2002 Apr	11927496
Serial first- and second-trimester Down's syndrome screening tests among IVF-versus naturally-conceived singletons.	2002 Apr	11925409
Ligand-specific regulation of proteasome-mediated proteolysis of estrogen receptor-alpha.	2002 Apr	11882509
Fetal diaphragmatic hernia and upper limb anomalies suggest Brachmann-de Lange syndrome.	2002 Feb	11857622
A negative second trimester triple test and absence of specific ultrasonographic markers may decrease the need for genetic amniocentesis in advanced maternal age by 60%.	2002 Jan	11810653
Plasma corticotropin-releasing hormone and unconjugated estriol in human pregnancy: gestational patterns and ability to predict preterm delivery.	2002 Jan	11810092
Effect of various oestrogens on cell injury and alteration of apical transporters induced by tert-butyl hydroperoxide in renal proximal tubule cells.	2002 Jan-Feb	11906461
Pregnancy outcomes of women with positive serum screening results for Down syndrome and trisomy 18.	2002 Mar	11920909
Correlation of ultrasound findings and biochemical markers in the second trimester of pregnancy in fetuses with trisomy 21.	2002 Mar	11920888
Topical estrogens combined with argon plasma coagulation in the management of epistaxis in hereditary hemorrhagic telangiectasia.	2002 Mar	11913682
Information from your family doctor. Triple screening in pregnancy--what it is and what to expect.	2002 Mar 1	11898966
Maternal serum triple analyte screening in pregnancy.	2002 Mar 1	11898965
Estradiol, testosterone, dehydroepiandrosterone and androstenedione: novel derivatives and enantiomers. Interactions with rat liver microsomal cytochrome P450 and antioxidant/radical scavenger activities in vitro.	2002 Mar 10	11869824

Patents

Sample Use Guides

In Vivo Use Guide

1 g/daily of the vaginal gel containing 50 μg of estriol (0.005%) for 3 weeks and then twice weekly for 9 weeks, for a complete cycle of treatment of 12 weeks

Route of Administration: Vaginal

In Vitro Use Guide

TNBC cell lines HCC1806, HCC70 and MDA-MB-231 were used for activity evaluation. For stimulation of TNBC cells to analyze signal transduction of GPR30, 4×106 cells were plated in culture medium into 25 cm2 -culture flasks. After attachment, cells were serum starved for 24 hours to synchronize the 17β- estradiol-starved cells in G0-phase. Serum starved cells were treated for 30 minutes either with 10^−4 M estriol or solvent (0.1% ethanol) and subsequently stimulated with 10^−8 M 17β-estradiol in 0.1% ethanol for 10 min or 20 minutes. Cells were harvested and cell pellets lysed in 100 μl Cell lytic M (Sigma, Deisendorf, Germany), supplemented with protease-inhibitor (Sigma, Deisendorf, Germany) and phosphatase-inhibitor (Sigma, Deisendorf, Germany).

Name

Type

Language

ESTRIOL SUCCINATE

Official Name

English

estriol succinate [INN]

Common Name

English

Estriol succinate [WHO-DD]

Common Name

English

ESTRIOL SUCCINATE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2181