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Details

Stereochemistry ABSOLUTE
Molecular Formula 2C18H24O2.H2O
Molecular Weight 562.7806
Optical Activity UNSPECIFIED
Defined Stereocenters 10 / 10
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ESTRADIOL HEMIHYDRATE

SMILES

C[C@@]12CC[C@]3([H])c4ccc(cc4CC[C@@]3([H])[C@]2([H])CC[C@]1([H])O)O.C[C@@]12CC[C@]3([H])c4ccc(cc4CC[C@@]3([H])[C@]2([H])CC[C@]1([H])O)O.O

InChI

InChIKey=ZVVGLAMWAQMPDR-WVEWYJOQSA-N
InChI=1S/2C18H24O2.H2O/c2*1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20;/h2*3,5,10,14-17,19-20H,2,4,6-9H2,1H3;1H2/t2*14-,15-,16+,17+,18+;/m11./s1

HIDE SMILES / InChI

Molecular Formula C18H24O2
Molecular Weight 272.3826
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Gene Symbol: STS
Target Organism: Homo sapiens (Human)
0.00839999999999999948 nM [EC50]
1.39999999999999991 nM [EC50]
19.1000000000000014 nM [IC50]
0.130000000000000004 nM [Ki]
0.0899999999999999967 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

157680000000
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

157680000000
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

157680000000
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
Indole-3-carbinol is a negative regulator of estrogen receptor-alpha signaling in human tumor cells.
2000 Dec
Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene.
2000 Nov
Female sex steroids: effects upon microglial cell activation.
2000 Nov 1
Estradiol enhances the resistance of LDL to oxidation by stabilizing apoB-100 conformation.
2000 Nov 14
Relative binding affinity does not predict biological response to xenoestrogens in rat endometrial adenocarcinoma cells.
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
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
Effects of follicle-stimulating hormone with and without luteinizing hormone on serum hormone concentrations, follicle growth, and intrafollicular estradiol and aromatase activity in gonadotropin-releasing hormone-immunized heifers.
2001 Jan
Female steroid hormones modulate receptors for nerve growth factor in rat dorsal root ganglia.
2001 Jan
Regulation and role of vascular endothelial growth factor in the corpus luteum during mid-pregnancy in rats.
2001 Jan
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
Follicle selection in cattle: role of luteinizing hormone.
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
Comparison of histological compositions and apoptosis in canine spontaneous benign prostatic hyperplasia treated with androgen suppressive agents chlormadinone acetate and finasteride.
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
Oestrogen-induced changes in the synaptology of the monkey (Cercopithecus aethiops) arcuate nucleus during gonadotropin feedback.
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
Evaluation of an EIA method for measuring serum levels of the estrogen metabolite 2-hydroxyestrone in adults.
2001 Jan
Estradiol levels in psychotic disorders.
2001 Jan
Effects of heterocyclic amines with mammary gland carcinogenic potential on estrogenic response of uterus in ovariectomized rats.
2001 Jan 10
Reduction of gamma-aminobutyric acid-ergic neurotransmission as a putative mechanism of radiation induced activation of the gonadotropin releasing-hormone-pulse generator leading to precocious puberty in female rats.
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
Evaluation of Effects of Topical Estradiol Benzoate Application on Cutaneous Wound Healing in Ovariectomized Female Mice.
2016
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 Vitro Use Guide
The influence of estradiol benzoate on the proliferation of bone cells was investigated in vitro. The fibulae from 19-day fetal rats were pulse-labeled with 3H-thymidine after various periods of culture on estrogen-supplemented (5 microgram/ml) or control media. The analysis revealed that the cell division was restricted to osteogenic cells of undifferentiated appearance. No label was found in osteoblasts or in osteoclasts. At the time of explantation, about 30% of osteogenic cells were labeled. However, this percentage varied considerably after different intervals of culture. In the control bones, it decreased during first 12 hours to 15% and then rose slowly to attain a preculture value after 48 hours. In the presence of estradiol, the initial decline of labeled cells was less pronounced. The percentage recovered to a preculture level already after 24 hours and continued to increase thereafter. The numbers of labeled osteogenic cells, in estrogen-treated bones, were significantly higher than in controls already after 12 hours of culture. It is concluded that the fetal rat bones undergo in vitro a period of adaptation to a new environment as indicated by a transient decrease of dividing cells. Estradiol benzoate appears to shorten this period by stimulating the proliferation of undifferentiated cells.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:17:37 UTC 2021
Edited
by admin
on Fri Jun 25 21:17:37 UTC 2021
Record UNII
CXY7B3Q98Z
Record Status Validated (UNII)
Record Version
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Name Type Language
ESTRADIOL HEMIHYDRATE
EP   MI   ORANGE BOOK   WHO-DD  
Common Name English
ESTRADIOL HEMIHYDRATE [MI]
Common Name English
ESTRASORB
Brand Name English
MYFEMBREE COMPONENT ESTRADIOL HEMIHYDRATE
Brand Name English
ESTRADIOL HEMIHYDRATE [WHO-DD]
Common Name English
ESTRADIOL HEMIHYDRATE [ORANGE BOOK]
Common Name English
ESTRADIOL HEMIHYDRATE [EP MONOGRAPH]
Common Name English
ESTRADIOL HEMIHYDRATE COMPONENT OF MYFEMBREE
Brand Name English
(17.BETA.)-ESTRA-1,3,5(10)-TRIENE-3,17-DIOL HEMIHYDRATE
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS ZOELY (AUTHORIZED: CONTRACEPTION)
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
EU-Orphan Drug EU/3/05/275
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
NCI_THESAURUS C478
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
Code System Code Type Description
DRUG BANK
DBSALT001383
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
PRIMARY
RXCUI
236859
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
PRIMARY RxNorm
PUBCHEM
154274
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
PRIMARY
FDA UNII
CXY7B3Q98Z
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
PRIMARY
WIKIPEDIA
Estradiol hemihydrate
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
PRIMARY
ChEMBL
CHEMBL135
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
PRIMARY
NCI_THESAURUS
C47992
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
PRIMARY
MERCK INDEX
M5028
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
PRIMARY Merck Index
EVMPD
SUB11941MIG
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
PRIMARY
CAS
35380-71-3
Created by admin on Fri Jun 25 21:17:37 UTC 2021 , Edited by admin on Fri Jun 25 21:17:37 UTC 2021
PRIMARY
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
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IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 0.4
CHROMATOGRAPHIC PURITY (HPLC/UV)
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