POTASSIUM ESTRONE SULFATE

First marketed in 1931

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H21O5S.K
Molecular Weight	388.52
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[K+].[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=CUQHOFAEIPGLBH-ZFINNJDLSA-M

InChI=1S/C18H22O5S.K/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);/q;+1/p-1/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
Reproducibility of plasma and urinary sex hormone levels in premenopausal women over a one-year period.	1999 Dec	10613337
Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain.	1999 May 7	10224140
Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta.	2000 Feb 11	10660625
Atheroprotective effect of estriol and estrone sulfate on human vascular smooth muscle cells.	2000 Jan-Feb	10731640
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
Flaxseed consumption influences endogenous hormone concentrations in postmenopausal women.	2001	11588903
Estrone, but not 17 beta-estradiol, attenuates kainate-induced seizures and toxicity in male mice.	2001	11409300
Futile cycling of estrone sulfate and estrone in the recirculating perfused rat liver preparation.	2001 Apr	11259571
Prospective randomized study of effects of unopposed estrogen replacement therapy on markers of coagulation and inflammation in postmenopausal women.	2001 Aug	11502788
Synthesis of ring B unsaturated estriols. Confirming the structure of a diagnostic analyte for Smith-Lemli-Opitz syndrome.	2001 Aug 9	11483057
[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
Equine estrogen metabolite 4-hydroxyequilenin induces DNA damage in the rat mammary tissues: formation of single-strand breaks, apurinic sites, stable adducts, and oxidized bases.	2001 Dec	11743748
Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver.	2001 Feb	11159893
Inhibition of postmenopausal atherosclerosis progression: a comparison of the effects of conjugated equine estrogens and soy phytoestrogens.	2001 Jan	11231976
Effects of estrone sulfate alone or with medroxyprogesterone acetate on serum lipoprotein levels in postmenopausal women.	2001 Jan	11152917
Hepatic uptake of synthetic chlorogenic acid derivatives by the organic anion transport proteins.	2001 Jan	11123367
Sleep in menopause: differential effects of two forms of hormone replacement therapy.	2001 Jan-Feb	11201509
Synthesis and steroid sulphatase inhibitory activity of C19- and C21-steroidal derivatives bearing a benzyl-inhibiting group.	2001 Jul-Aug	11600235
Synthesis and reactivity of the catechol metabolites from the equine estrogen, 8,9-dehydroestrone.	2001 Jun	11409947
Oral gavage of oleoyl-oestrone has a stronger effect on body weight in male Zucker obese rats than in female.	2001 Jun	11412285
Increased prostacyclin synthesis by atherosclerotic arteries from estrogen-treated monkeys.	2001 Jun 15	11459430
[Effects of exposure to low-level benzene and its analogues on reproductive hormone secretion in female workers].	2001 Mar	11413688
Functional analysis and androgen-regulated expression of mouse organic anion transporting polypeptide 1 (Oatp1) in the kidney.	2001 Mar 19	11267661
Glutathione stimulates sulfated estrogen transport by multidrug resistance protein 1.	2001 Mar 2	11102445
Actions of the soy phytoestrogen genistein in models of human chronic disease: potential involvement of transforming growth factor beta.	2001 May	11356157
Influence of culture system and medium enrichment on sulfotransferase and sulfatase expression in male rat hepatocyte cultures.	2001 May 1	11301044
Serum hormones and the alcohol-breast cancer association in postmenopausal women.	2001 May 2	11333294
Markedly elevated levels of estrone sulfate after long-term oral, but not transdermal, administration of estradiol in postmenopausal women.	2001 May-Jun	11355042
Endocrinology of gynaecomastia.	2001 Nov	11732643
Short-term oral estrogen replacement therapy does not augment endothelium-independent myocardial perfusion in postmenopausal women.	2001 Oct	11579354
Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans.	2001 Sep 21	11477075
Hormone replacement therapy for cognitive function in postmenopausal women.	2002	12137675
Characterization of an organic anion-transporting polypeptide (OATP-B) in human placenta.	2002 Apr	11932330
Hormonal measurements in late pregnancy and parturition in dairy cows--possible tools to monitor foetal well being.	2002 Aug 15	12137978
Transcellular transport of organic anions across a double-transfected Madin-Darby canine kidney II cell monolayer expressing both human organic anion-transporting polypeptide (OATP2/SLC21A6) and Multidrug resistance-associated protein 2 (MRP2/ABCC2).	2002 Feb 22	11748225
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
Impaired organic anion transport in kidney and choroid plexus of organic anion transporter 3 (Oat3 (Slc22a8)) knockout mice.	2002 Jul 26	12011098
Nonsteroidal compounds designed to mimic potent steroid sulfatase inhibitors.	2002 Mar	11948019
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
The IGF-system in healthy pre- and postmenopausal women: relations to demographic variables and sex-steroids.	2002 May	12127047
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
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

POTASSIUM ESTRONE SULFATE

Common Name

English

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

Common Name

English

NSC-18054

Code

English

Code System Code Type Description

MESH

C017296