U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H28O3
Molecular Weight 376.488
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ESTRADIOL BENZOATE

SMILES

[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]3([H])C4=CC=C(OC(=O)C5=CC=CC=C5)C=C4CC[C@@]23[H]

InChI

InChIKey=UYIFTLBWAOGQBI-BZDYCCQFSA-N
InChI=1S/C25H28O3/c1-25-14-13-20-19-10-8-18(28-24(27)16-5-3-2-4-6-16)15-17(19)7-9-21(20)22(25)11-12-23(25)26/h2-6,8,10,15,20-23,26H,7,9,11-14H2,1H3/t20-,21-,22+,23+,25+/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020375s027lbl.pdf

Estradiol an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. In humans, it is produced primarily by the cyclic ovaries and the placenta. It is also produced by the adipose tissue of men and postmenopausal women. The 17-alpha-isomer of estradiol binds weakly to estrogen receptors (receptors, estrogen) and exhibits little estrogenic activity in estrogen-responsive tissues. Estradiol enters target cells freely (e.g., female organs, breasts, hypothalamus, pituitary) and interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. Estradiol is used for the treatment of urogenital symptoms associated with post-menopausal atrophy of the vagina (such as dryness, burning, pruritus and dyspareunia) and/or the lower urinary tract (urinary urgency and dysuria). Estradiol is marketed under the brand name Climara (among others), indicated for: the treatment of moderate to severe vasomotor symptoms due to menopause, treatment of symptoms of vulvar and vaginal atrophy due to menopause, treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure and prevention of postmenopausal osteoporosis.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P08842
Gene ID: 412.0
Gene Symbol: STS
Target Organism: Homo sapiens (Human)
0.0084 nM [EC50]
1.4 nM [EC50]
19.1 nM [IC50]
0.13 nM [Ki]
0.09 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CLIMARA

Approved Use

Climara is an estrogen indicated for: •Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause •Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause •Treatment of Hypoestrogenism due to Hypogonadism, Castration or Primary Ovarian Failure •Prevention of Postmenopausal Osteoporosis

Launch Date

1974
Preventing
CLIMARA

Approved Use

Climara is an estrogen indicated for: •Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause •Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause •Treatment of Hypoestrogenism due to Hypogonadism, Castration or Primary Ovarian Failure •Prevention of Postmenopausal Osteoporosis

Launch Date

1974
Primary
CLIMARA

Approved Use

Climara is an estrogen indicated for: •Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause •Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause •Treatment of Hypoestrogenism due to Hypogonadism, Castration or Primary Ovarian Failure •Prevention of Postmenopausal Osteoporosis

Launch Date

1974
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
14.7 pg/mL
0.25 mg 1 times / day steady-state, topical
dose: 0.25 mg
route of administration: Topical
experiment type: STEADY-STATE
co-administered:
ESTRADIOL plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE
food status: UNKNOWN
92 pg/mL
0.05 mg 1 times / day multiple, topical
dose: 0.05 mg
route of administration: Topical
experiment type: MULTIPLE
co-administered:
ESTRADIOL plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
236 pg × h/mL
0.25 mg 1 times / day steady-state, topical
dose: 0.25 mg
route of administration: Topical
experiment type: STEADY-STATE
co-administered:
ESTRADIOL plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10 h
0.25 mg 1 times / day steady-state, topical
dose: 0.25 mg
route of administration: Topical
experiment type: STEADY-STATE
co-administered:
ESTRADIOL plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE
food status: UNKNOWN
1.75 h
0.05 mg 1 times / day multiple, topical
dose: 0.05 mg
route of administration: Topical
experiment type: MULTIPLE
co-administered:
ESTRADIOL plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
minor
minor
minor
minor
minor
minor
no
no
no
no
no
no
no
no
no
yes [Km 7 uM]
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Effect of estradiol benzoate on the proliferation of osteogenic cells in fetal rat fibulae cultured in vitro.
1978 Mar
An increase of pituitary 3', 5' cyclic adenosine monophosphate produced by estradiol benzoate in vitro: possible implication of this increase in the secretion of luteinizing hormone.
1978 May
Sulfation of estrone and 17 beta-estradiol in human liver. Catalysis by thermostable phenol sulfotransferase and by dehydroepiandrosterone sulfotransferase.
1992 May-Jun
[The effect of adrenaline and 17beta-estradiol sulfate on transmembrane potentials of guinea pig cardiomyocytes].
1996 Dec
Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta.
1997 Mar
Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta.
1998 Oct
WISP-2 as a novel estrogen-responsive gene in human breast cancer cells.
2000 Aug 18
Indole-3-carbinol is a negative regulator of estrogen receptor-alpha signaling in human tumor cells.
2000 Dec
Differential effects of xenoestrogens on coactivator recruitment by estrogen receptor (ER) alpha and ERbeta.
2000 Nov 17
Changes in serum and tissue zinc levels in sex hormone-induced prostatic carcinogenesis in the noble rat.
2000 Nov-Dec
Relative binding affinity does not predict biological response to xenoestrogens in rat endometrial adenocarcinoma cells.
2000 Oct
Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta.
2000 Oct
Effects of arsenite on estrogen receptor-alpha expression and activity in MCF-7 breast cancer cells.
2000 Oct
Antiestrogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mouse uterus: critical role of the aryl hydrocarbon receptor in stromal tissue.
2000 Oct
Repression of chick multidrug resistance-associated protein 1 (chMRP1) gene expression by estrogen.
2000 Oct 31
NADPH- and hydroperoxide-supported 17beta-estradiol hydroxylation catalyzed by a variant form (432L, 453S) of human cytochrome P450 1B1.
2000 Sep
Constitutive expression of the steroid sulfatase gene supports the growth of MCF-7 human breast cancer cells in vitro and in vivo.
2001 Apr
Hormone status selects for spontaneous somatic androgen receptor variants that demonstrate specific ligand and cofactor dependent activities in autochthonous prostate cancer.
2001 Apr 6
Vitellogenin-induced pathology in male summer flounder (Paralichthys dentatus).
2001 Feb
Use of salivary biomarkers in biobehavioral research: cotton-based sample collection methods can interfere with salivary immunoassay results.
2001 Feb
Unique protein determinants of the subtype-selective ligand responses of the estrogen receptors (ERalpha and ERbeta ) at AP-1 sites.
2001 Feb 9
Increased expression of a novel heat shock protein transcript in the mouse uterus during decidualization and in response to progesterone.
2001 Jan
Regulation of progesterone receptors and decidualization in uterine stroma of the estrogen receptor-alpha knockout mouse.
2001 Jan
Pregnancy stimulates secretion of adrenocorticotropin and nitric oxide from peripheral bovine lymphocytes.
2001 Jan
Lysyl oxidase and MMP-2 expression in dehydroepiandrosterone-induced polycystic ovary in rats.
2001 Jan
Changes in follicle-stimulating hormone and follicle populations during the ovarian cycle of the common marmoset.
2001 Jan
Estradiol-induced attenuation of pulmonary hypertension is not associated with altered eNOS expression.
2001 Jan
Metabolism of estradiol, ethynylestradiol, and moxestrol in rat uterus, vagina, and aorta: influence of sex steroid treatment.
2001 Jan
Sex steroid hormones enhance immune function in male and female Siberian hamsters.
2001 Jan
Rapid and reversible inhibition of brain aromatase activity.
2001 Jan
Stimulatory effect of clofibrate and gemfibrozil administration on the formation of fatty acid esters of estradiol by rat liver microsomes.
2001 Jan
Influence of gender and sex hormones on nicotine acute pharmacological effects in mice.
2001 Jan
Heat-shock factor-1, steroid hormones, and regulation of heat-shock protein expression in the heart.
2001 Jan
Gender-related distinctions in protein kinase C activity in rat vascular smooth muscle.
2001 Jan
Dose-response relationships and pharmacokinetics of vitellogenin in rainbow trout after intravascular administration of 17alpha-ethynylestradiol.
2001 Jan
Estradiol levels in psychotic disorders.
2001 Jan
Neuroprotection by estradiol.
2001 Jan
Effects of heterocyclic amines with mammary gland carcinogenic potential on estrogenic response of uterus in ovariectomized rats.
2001 Jan 10
Hormone binding by protein disulfide isomerase, a high capacity hormone reservoir of the endoplasmic reticulum.
2001 Jan 5
Acquisition of Lubrol insolubility, a common step for growth hormone and prolactin in the secretory pathway of neuroendocrine cells.
2001 Jan 5
In vivo regulation of syndecan-3 expression in the rat uterus by 17 beta-estradiol.
2001 Jan 5
Glutathione stimulates sulfated estrogen transport by multidrug resistance protein 1.
2001 Mar 2
Estrogen decreases osteoclast formation by down-regulating receptor activator of NF-kappa B ligand (RANKL)-induced JNK activation.
2001 Mar 23
Enhanced multispecificity of arabidopsis vacuolar multidrug resistance-associated protein-type ATP-binding cassette transporter, AtMRP2.
2001 Mar 23
The unusual binding properties of the third distinct teleost estrogen receptor subtype ERbetaa are accompanied by highly conserved amino acid changes in the ligand binding domain.
2004 Jun
Sulfonation of 17beta-estradiol and inhibition of sulfotransferase activity by polychlorobiphenylols and celecoxib in channel catfish, Ictalurus punctatus.
2007 Mar 10
Complex actions of estradiol-3-sulfate in late gestation fetal brain.
2011 Jul
[Study of gonadal hormone drugs in blocking filovirus entry of cells in vitro].
2015 Dec
Effects of Exposure to Estradiol Benzoate or Flutamide at the Weaning Age on Expression of Connexins in the Caudal Epididymis of Adult Rat.
2016 Dec
Changes in Expression of Connexin Isoforms in the Caudal Epididymis of Adult Sprague-Dawley Rats exposed to Estradiol Benzoate or Flutamide at the Neonatal Age.
2016 Sep
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Estradiol benzoate is not approved by the FDA for use in humans in the United States.
Unknown
Route of Administration: Unknown
Estradiol-3-sulfate (E2SO4) infused intracerebroventricularly (icv) significantly increased plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations. All minipumps in the treated fetuses were filled with E2SO4 in the vehicle (water) and minipumps in the control fetuses were filled with vehicle only. These minipumps deliver a constant infusion of 5 μL/h; the concentration of E2SO4 in infusates was therefore 8.33 μg/μL. It was concluded, that E2SO4 had complex actions on the fetal brain, which might involve deconjugation by steroid sulfatase. But that the net result of direct E2SO4 icv infusion was more complex than could be accounted for by infusion of E2 alone.
Name Type Language
ESTRADIOL BENZOATE
EP   GREEN BOOK   INN   MART.   USP   USP-RS   WHO-DD  
INN  
Official Name English
estradiol benzoate [INN]
Common Name English
ESTRADIOL BENZOATE [GREEN BOOK]
Common Name English
ESTRADIOL BENZOATE [MART.]
Common Name English
ESTRADIOL BENZOATE [USP-RS]
Common Name English
OESTRADIOL BENZOATE
Common Name English
ESTRADIOL BENZOATE [USP IMPURITY]
Common Name English
ESTRADIOL 3-BENZOATE [MI]
Common Name English
NSC-9566
Code English
ESTRADIOL BENZOATE [JAN]
Common Name English
Estradiol 3-benzoate
MI  
Common Name English
ESTRADIOL BENZOATE [USP MONOGRAPH]
Common Name English
Estradiol benzoate [WHO-DD]
Common Name English
ESTRADIOL BENZOATE [EP MONOGRAPH]
Common Name English
Classification Tree Code System Code
CFR 21 CFR 522.1940
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
NCI_THESAURUS C478
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
CFR 21 CFR 522.842
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
CFR 21 CFR 522.2478
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID9022998
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
SMS_ID
100000085434
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
RS_ITEM_NUM
1251000
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
ECHA (EC/EINECS)
200-043-7
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
EVMPD
SUB07243MIG
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
CAS
50-50-0
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
NSC
9566
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
RXCUI
60661
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY RxNorm
PUBCHEM
222757
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
MESH
C074283
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
FDA UNII
1S4CJB5ZGN
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
MERCK INDEX
m5028
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY Merck Index
DAILYMED
1S4CJB5ZGN
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
ChEMBL
CHEMBL282575
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
INN
405
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
CHEBI
77006
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
DRUG BANK
DB13953
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
NCI_THESAURUS
C29769
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
DRUG CENTRAL
1058
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY
WIKIPEDIA
Estradiol benzoate
Created by admin on Fri Dec 15 15:16:09 GMT 2023 , Edited by admin on Fri Dec 15 15:16:09 GMT 2023
PRIMARY