ESTRONE SULFATE

First marketed in 1931

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H22O5S
Molecular Weight	350.429
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=JKKFKPJIXZFSSB-CBZIJGRNSA-N

InChI=1S/C18H22O5S/c1-18-9-8-14-13-5-3-12(23-24(20,21)22)10-11(13)2-4-15(14)16(18)6-7-17(18)19/h3,5,10,14-16H,2,4,6-9H2,1H3,(H,20,21,22)/t14-,15-,16+,18+/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.drugfuture.com/chemdata/estrone.html | http://pubs.acs.org/doi/abs/10.1021/ja01159a529?journalCode=jacsat | http://pubs.acs.org/doi/abs/10.1021/ja00536a023https://www.ncbi.nlm.nih.gov/pubmed/27960570 | https://www.accessdata.fda.gov/cdrh_docs/pdf/K970915.pdfhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=83dd22a0-7c59-11e6-84ff-424c58303031
Curator's Comment: description was created based on several sources, including http://www.drugbank.ca/drugs/DB00655 https://www.ncbi.nlm.nih.gov/pubmed/2011412 https://www.ncbi.nlm.nih.gov/pubmed/17943537

Estrone, one of the major mammalian estrogens, is an aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone. It is produced in vivo from androstenedione or from testosterone via estradiol. It is produced primarily in the ovaries, placenta, and in peripheral tissues (especially adipose tissue) through conversion of adrostenedione. Estrone may be further metabolized to 16-alpha-hydroxyestrone, which may be reduced to estriol by estradiol dehydrogenase. It’s used as hameopatic in management of premenopausal and postmenopausal symptoms. In 1929, Butenandt isolated estrone from the urine of pregnant women. Estrone is known to be a carcinogen for human females as well as a cause of breast tenderness or pain, nausea, headache, hypertension, and leg cramps in the context of non-endogenous exposure. In men, estrone has been known to cause anorexia, nausea, vomiting, and erectile dysfunction. Estrone is relevant to health and disease states because of its conversion to estrone sulfate, a long-lived derivative. Estrone sulfate acts as a reservoir that can be converted as needed to the more active estradiol.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor alpha 127 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6863279 \| https://www.ncbi.nlm.nih.gov/pubmed/15081034	Agonist 2678		7.0 nM [EC50]
Estrogen receptor alpha 127 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2011412	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27960570	Diagnostic	Natural Metabolite	Unknown Approved Use Unknown
Benign breast disease 7 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27960570	Diagnostic	Natural Metabolite	Unknown Approved Use Unknown
Endometrial cancer 43 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27960570	Diagnostic	Natural Metabolite	Unknown Approved Use Unknown
Prostate cancer 178 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27960570	Diagnostic	Natural Metabolite	Unknown Approved Use Unknown
Obesity 203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27960570	Diagnostic	Natural Metabolite	Unknown Approved Use Unknown
Infertility 14 Sources: https://www.accessdata.fda.gov/cdrh_docs/pdf/K970915.pdf	Diagnostic	Natural Metabolite	Unknown Approved Use Unknown
Amenorrhea 18 Sources: https://www.accessdata.fda.gov/cdrh_docs/pdf/K970915.pdf	Diagnostic	Natural Metabolite	Unknown Approved Use Unknown
Ovarian diseases 7 Sources: https://www.accessdata.fda.gov/cdrh_docs/pdf/K970915.pdf	Diagnostic	Natural Metabolite	Unknown Approved Use Unknown
Precocious puberty 8 Sources: https://www.accessdata.fda.gov/cdrh_docs/pdf/K970915.pdf	Diagnostic	Natural Metabolite	Unknown Approved Use Unknown
Menopausal and postmenopausal disorder 10 Sources: http://www.rxlist.com/estragyn-drug.htm http://chealth.canoe.com/drug/getdrug/estragyn-vaginal-cream https://www.drugs.com/international/estrone.html	Primary	Approved 8429	Estragyn Approved Use Estragyn Vaginal Cream is prescribed in the treatment of menopausal and post menopausal symptoms. Estragyn Vaginal Cream should be prescribed with an appropriate dosage of a progestin for women with intact uteri to prevent endometrial hyperplasia/carcinoma.
Endometrial hyperplasia/carcinoma 7 Sources: http://www.rxlist.com/estragyn-drug.htm http://chealth.canoe.com/drug/getdrug/estragyn-vaginal-cream https://www.drugs.com/international/estrone.html	Primary	Approved 8429	Estragyn Approved Use Estragyn Vaginal Cream is prescribed in the treatment of menopausal and post menopausal symptoms. Estragyn Vaginal Cream should be prescribed with an appropriate dosage of a progestin for women with intact uteri to prevent endometrial hyperplasia/carcinoma.
Menopausal and postmenopausal disorders 7 Sources: http://www.druglib.com/activeingredient/estrone/	Primary	Approved 8429	THEELIN Approved Use For management of Menopausal and postmenopausal disorders
Premenstrual syndrome 37 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=83dd22a0-7c59-11e6-84ff-424c58303031	Palliative	Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
733 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/908445/	0.5 mg single, vaginal dose: 0.5 mg route of administration: Vaginal experiment type: SINGLE co-administered:		ESTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
550 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/908445/	0.5 mg single, vaginal dose: 0.5 mg route of administration: Vaginal experiment type: SINGLE co-administered:		ESTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/908445/	0.5 mg single, vaginal dose: 0.5 mg route of administration: Vaginal experiment type: SINGLE co-administered:		ESTRONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP3A5 395 P-gp 1537 UGT1A10 291 UGT1A3 422 UGT2A1 32 CYP1A1 349 CYP1A2 1054 CYP2B6 664 CYP2E1 667	P-gp 257

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/15290871/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26220143/	major
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10640505/	no
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26220143/	weak
UGT2A1 32	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26220143/	weak
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10640505/	yes
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10640505/	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9625734/	yes
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/10640505/	yes
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9635876/	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15290871/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9625734/	yes	weak (co-administration study) Comment: Coadministration with ketoconazole (CYP3A4 inhibitor) resulted in estrone expsoure increase of ~1.4 foold Sources: https://pubmed.ncbi.nlm.nih.gov/9625734/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/19129680/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:17263	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:17263
ChemicalBook	CB5741416	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5741416
MolPort	MolPort-001-742-529	https://www.molport.com/shop/molecule-link/MolPort-001-742-529
Selleck Chemicals	Estrone	http://www.selleckchem.com/products/Estrone.html
ZINC	ZINC000013509425	http://zinc15.docking.org/substances/ZINC000013509425
eMolecules	29543531	https://www.emolecules.com/cgi-bin/more?vid=29543531
eMolecules	511617	https://www.emolecules.com/cgi-bin/more?vid=511617

PubMed

Title	Date	PubMed
Biological effects of hormone replacement therapy in relation to serum estradiol levels.	2001	11815726
Estrogen sulfamates: a new approach to oral estrogen therapy.	2001	11800168
[Effects of oral administration of estrogen replacement therapy in surgical menopause].	2001 Dec	11883282
Comparison of estrogen and androgen levels after oral estrogen replacement therapy.	2001 Dec	11789085
Estrogen replacement therapy after breast cancer: a 12-year follow-up.	2001 Dec	11776498
The antihyperglycemic effect of estrone sulfate in genetically obese-diabetic (ob/ob) mice is associated with reduced hepatic glucose-6-phosphatase.	2001 Dec	11753757
By the way, Doctor. Whenever I read about the effects of hormone replacement therapy (HRT), the researchers always seem to use 0.625 mg of Premarin. I'm taking 1 mg of Estrace daily. How does this compare to the standard dose of Premarin?	2001 Dec	11751102
Effect of transforming growth factor-beta1, insulin-like growth factor-I and insulin-like growth factor-II on cell growth and oestrogen metabolism in human breast cancer cell lines.	2001 Nov	11827412
[Prevention and treatment of recurrent urinary system infection with estrogen cream in postmenopausal women].	2001 Sep	11769665
Hormone replacement therapy for cognitive function in postmenopausal women.	2002	12137675
Induction of puberty in the hypogonadal girl--practices and attitudes of pediatric endocrinologists in Europe.	2002	12006724
The role of cytokines in regulating estrogen synthesis: implications for the etiology of breast cancer.	2002	11879566
Synthesis and biochemical evaluation of novel and potent inhibitors of the enzyme oestrone sulphatase (ES).	2002 Apr	11983489
Number of years since menopause: spontaneous bone loss is dependent but response to hormone replacement therapy is independent.	2002 Apr	11934658
Characterization of an organic anion-transporting polypeptide (OATP-B) in human placenta.	2002 Apr	11932330
Bone loss at the femoral neck in premenopausal white women: effects of weight change and sex-hormone levels.	2002 Apr	11932278
An evolutionarily ancient Oatp: insights into conserved functional domains of these proteins.	2002 Apr	11897630
Peripheral changes in estrone sulfate concentration during the first trimester of gestation in cattle: comparison with unconjugated estrogens and relationship to fetal number.	2002 Apr 15	12041697
Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies.	2002 Apr 17	11959894
Evidence for carrier-mediated transport of unconjugated bilirubin across plasma membrane vesicles from human placental trophoblast.	2002 Aug	12175967
Hormonal measurements in late pregnancy and parturition in dairy cows--possible tools to monitor foetal well being.	2002 Aug 15	12137978
Functional characterization of the mouse organic-anion-transporting polypeptide 2.	2002 Aug 19	12101011
A randomized isoflavone intervention among premenopausal women.	2002 Feb	11867507
Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study.	2002 Feb 1	11821457
Review of estrone sulfatase and its inhibitors--an important new target against hormone dependent breast cancer.	2002 Jan	11860358
Endocrine changes in late bovine pregnancy with special emphasis on fetal well-being.	2002 Jul	12142248
The bovine placenta; a source and target of steroid hormones: observations during the second half of gestation.	2002 Jul	12142247
Mammary secretion of oestrogens in the cow.	2002 Jul	12142232
Does place of birth influence endogenous hormone levels in Asian-American women?	2002 Jul 1	12085256
Role of aromatic transmembrane residues of the organic anion transporter, rOAT3, in substrate recognition.	2002 Jul 16	12102636
Impaired organic anion transport in kidney and choroid plexus of organic anion transporter 3 (Oat3 (Slc22a8)) knockout mice.	2002 Jul 26	12011098
A naturally occurring mutation in MRP1 results in a selective decrease in organic anion transport and in increased doxorubicin resistance.	2002 Jun	12042670
Alveolar and postcranial bone density in postmenopausal women receiving hormone/estrogen replacement therapy: a randomized, double-blind, placebo-controlled trial.	2002 Jun 24	12076241
Nonsteroidal compounds designed to mimic potent steroid sulfatase inhibitors.	2002 Mar	11948019
Approval summary: letrozole in the treatment of postmenopausal women with advanced breast cancer.	2002 Mar	11895893
Characterization of iodothyronine sulfatase activities in human and rat liver and placenta.	2002 Mar	11861502
Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1.	2002 Mar 8	12005172
Interaction of human organic anion transporters with various cephalosporin antibiotics.	2002 Mar 8	11909604
The IGF-system in healthy pre- and postmenopausal women: relations to demographic variables and sex-steroids.	2002 May	12127047
Specific radioimmunoassay of estrone sulfate. Application to measurement in male plasma.	2002 May	12127046
Estrogens affect endothelin-1 mRNA expression in LNCaP human prostate carcinoma cells.	2002 May	12074801
Effects of lactation length and an exogenous progesterone and estradiol-17beta regimen during embryo attachment on endogenous steroid concentrations and embryo survival in sows.	2002 May	12066866
The choice of hormone replacement therapy or statin therapy in the treatment of hyperlipidemic postmenopausal women.	2002 May	12044587
Conformational analysis of a 4-hydroxyequilenin Guanine adduct using density functional theory.	2002 May	12018985
Endometrial thickness and uterine diameter not affected by ultralow doses of 17beta-estradiol in elderly women.	2002 May	12015519
Association of CYP1B1 polymorphisms and breast cancer risk.	2002 May	12010864
Transport of the sulfated, amidated bile acid, sulfolithocholyltaurine, into rat hepatocytes is mediated by Oatp1 and Oatp2.	2002 May	11981753
A new route to (+)-estrone using a bicyclo[3.2.1]octane chiral building block.	2003 Jan	12520140
Formal enantioselective synthesis of (+)-estrone.	2007 Mar 15	17295499
Catalytic asymmetric Torgov cyclization: a concise total synthesis of (+)-estrone.	2014 Aug 11	25080299

Patents

Sample Use Guides

In Vivo Use Guide

Estrone is available in the following doses: Estrone 2 Mg/ml Intramuscular Solution Estrone 5 Mg/ml Intramuscular Solution Estrone Compounding Powder Forms of Medication Estrone is available in the following forms: Injectable Solution Injectable Suspension Vaginal Suppository

Route of Administration: Intramuscular

In Vitro Use Guide

At 1.0 x 10(-8) M, estrone promoted growth of MTW9/PL cells established from the carcinogen-induced hormone-responsive MT-W9A rat mammary tumor of a Wistar-Furth (W/Fu) rat.

Name

Type

Language

ESTRONE SULFATE

Common Name

English

ESTRONE 3 SULFATE

Common Name

English

ESTRONE-3-SULFATE

Common Name

English

ESTRONE-3-SULPHATE

Common Name

English

ESTRONE, HYDROGEN SULFATE

Common Name

English

US-2917522

Code

English

ESTRONE SULFATE [MI]

Common Name

English

ESTRA-1,3,5(10)-TRIEN-17-ONE, 3-(SULFOOXY)-

Systematic Name

English

ESTRADIOL METABOLITE (E1S)

Common Name

English

ESTRA-1,3,5 (10)-TRIENE-17-ONE-3-YL-SULFATE

Common Name

English

ESTRONE BISULFATE

Common Name

English

CONJUGOL

Brand Name

English

PRICE

Brand Name

English

ESTRONE HEMISULFATE

Common Name

English

ESTRONE HYDROGEN SULFATE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2181