FOSFESTROL

US Previously Marketed

First approved in 1941

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H22O8P2
Molecular Weight	428.31
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC\C(C1=CC=C(OP(O)(O)=O)C=C1)=C(\CC)C2=CC=C(OP(O)(O)=O)C=C2

InChI

InChIKey=NLORYLAYLIXTID-ISLYRVAYSA-N

InChI=1S/C18H22O8P2/c1-3-17(13-5-9-15(10-6-13)25-27(19,20)21)18(4-2)14-7-11-16(12-8-14)26-28(22,23)24/h5-12H,3-4H2,1-2H3,(H2,19,20,21)(H2,22,23,24)/b18-17+

HIDE SMILES / InChI

Molecular Formula	C18H22O8P2
Molecular Weight	428.31
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: http://druginfosys.com/Drug.aspx?drugCode=327&drugName=&type=0https://www.drugs.com/mmx/stilbestrol.html
Curator's Comment: description was created based on several sources, including: http://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/083003.pdf | https://en.wikipedia.org/wiki/Diethylstilbestrol | http://monographs.iarc.fr/ENG/Monographs/vol100A/mono100A-16.pdf

Diethylstilbestrol is a synthetic non-steroidal estrogen. It is used in the treatment of menopausal and postmenopausal disorders, prostate cancer and in the prevention of miscarriage or premature delivery in pregnant women prone to miscarriage or premature delivery. Diethylstilbestrol is a very potent full agonist of the estrogen receptors. At the cellular level, estrogens increase the synthesis of DNA, RNA, and various proteins in target tissues. Pituitary mass is also increased. Estrogens reduce the release of gonadotropin-releasing hormone from the hypothalamus, leading to a reduction in release of follicle-stimulating hormone and luteinizing hormone from the pituitary. Adverse effects are: breast pain or tenderness, enlargement of breasts, gynecomastia, peripheral edema and others. Estrogens may interfere with the effects of bromocriptine. Dosage adjustment may be needed. Concurrent use with estrogens may alter the metabolism and protein binding of the glucocorticoids, leading to decreased clearance, increased elimination half-life, and increased therapeutic and toxic effects of the glucocorticoids.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Estrogen receptor alpha 134 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22294742	Agonist 2752	0.18 nM [EC50]
Estrogen receptor beta 113 Target ID: CHEMBL242 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22294742	Agonist 2752	0.06 nM [EC50]
Estrogen-related receptor alpha 12 Target ID: CHEMBL3429 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15161930 \| https://www.ncbi.nlm.nih.gov/pubmed/11447273	Inverse Agonist 85	10.0 µM [EC50]
Estrogen-related receptor beta 8 Target ID: CHEMBL3751 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11447273	Inverse Agonist 85	700.0 nM [EC50]
Estrogen-related receptor gamma 11 Target ID: CHEMBL4245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11447273	Inverse Agonist 85	700.0 nM [EC50]
estrogen receptor 1 5 Target ID: P03372 Gene Symbol: ESR1 Sources: http://www.drugbank.ca/drugs/DB00255	Agonist 2752
estrogen-related receptor alpha 5 Target ID: P11474 Gene Symbol: ESRRA Sources: http://genesdev.cshlp.org/content/15/7/833.full	Inverse Agonist 85	1.0 µM [IC50]
estrogen-related receptor beta 5 Target ID: O95718 Gene Symbol: ESRRB Sources: http://genesdev.cshlp.org/content/15/7/833.full	Inverse Agonist 85	1.0 µM [IC50]
estrogen-related receptor gamma 5 Target ID: P62508 Gene Symbol: ESRRG Sources: http://genesdev.cshlp.org/content/15/7/833.full	Inverse Agonist 85	1.0 µM [IC50]
estrogen receptor 2 (ER beta) 5 Target ID: Q92731 Gene Symbol: ESR2 Sources: http://www.drugbank.ca/drugs/DB00255	Agonist 2752

Conditions

Condition	Modality	Highest Phase	Product
Prostate cancer 186 Sources: http://www.drugbank.ca/drugs/DB00255	Primary	Approved 8583	Stilphostrol Approved Use Unknown Launch Date 1981
Prostate cancer 186 Sources: https://www.drugs.com/mmx/stilbestrol.html	Primary	Approved 8583	STILBESTROL Approved Use Used in the treatment of prostate cancer. Launch Date 1973
Miscarriage 5 Sources: http://monographs.iarc.fr/ENG/Monographs/vol100A/mono100A-16.pdf	Preventing	Approved 8583	STILBESTROL Approved Use Prevention of miscarriage or premature delivery in pregnant women prone to miscarriage or premature delivery. Launch Date 1973
Atrophic vaginitis 13 Sources: https://www.drugs.com/mmx/stilbestrol.html	Primary	Approved 8583	STILBESTROL Approved Use It is used for the treatment of senile (atrophic) vaginitis. Launch Date 1973
Vulvar dystrophy 5 Sources: https://www.drugs.com/mmx/stilbestrol.html	Primary	Approved 8583	STILBESTROL Approved Use It is used for the treatment of vulvar dystrophy. Launch Date 1973
Menopausal syndrome 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/083003.pdf	Primary	Approved 8583	STILBESTROL Approved Use Other therapeutic use of diethylstilbestrol was post menopause syndrome. Launch Date 1973
Amenorrhea 18 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/083003.pdf	Primary	Approved 8583	STILBESTROL Approved Use Drug is indicated for replacement therapy of estrogen deficiency associated with amenorrhea. Launch Date 1973
Female hypogonadism 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/083003.pdf	Primary	Approved 8583	STILBESTROL Approved Use Drug is indicated for replacement therapy of estrogen deficiency associated with female hypogonadism. Launch Date 1973
Postmenopausal osteoporosis 59 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/083003.pdf	Preventing	Approved 8583	STILBESTROL Approved Use Drug is indicated for the prevention of osteoporosis. Launch Date 1973

C_max

Value	Dose	Co-administered	Analyte	Population
5.64 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24618069/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		DIETHYLSTILBESTROL unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3672.44 pg/mL OTHER GOV'T https://mhraproducts4853.blob.core.windows.net/docs/2759709c34db666297f0c936bbe3b0acfc88fed4#page=9	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		DIETHYLSTILBESTROL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
9741.84 pg × h/mL OTHER GOV'T https://mhraproducts4853.blob.core.windows.net/docs/2759709c34db666297f0c936bbe3b0acfc88fed4#page=9	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		DIETHYLSTILBESTROL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
1500 mg 3 times / day multiple, oral Highest studied dose Dose: 1500 mg, 3 times / day Route: oral Route: multiple Dose: 1500 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/576887/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/576887/	Other AEs: Anorexia, Nausea... Other AEs: Anorexia (grade 1-3, 21.6%) Nausea (grade 1-3, 44%) Vomiting (grade 1-3, 24.1%) Diarrhea (grade 1-3, 6.9%) Peri-nipple pigmentation (grade 1-3, 16.4%) Uterine bleeding (grade 1-3, 4.3%) Withdrawal bleeding (grade 1-3, 3.4%) Hypercalcemia (grade 1-3, 5.2%) Edema (grade 1-3, 18.1%) Congestive heart failure (grade 1-3, 5.2%) Sources: https://pubmed.ncbi.nlm.nih.gov/576887/
1104 mg 1 times / day multiple, intravenous Recommended Dose: 1104 mg, 1 times / day Route: intravenous Route: multiple Dose: 1104 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12496896/	unhealthy, 56-87 Health Status: unhealthy Age Group: 56-87 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/12496896/	Disc. AE: Vomiting... AEs leading to discontinuation/dose reduction: Vomiting (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/12496896/
600 mg 1 times / day multiple, oral Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10526944/	unhealthy, 59 Health Status: unhealthy Age Group: 59 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/10526944/	Disc. AE: Secondary adrenocortical insufficiency... AEs leading to discontinuation/dose reduction: Secondary adrenocortical insufficiency Sources: https://pubmed.ncbi.nlm.nih.gov/10526944/
120 mg 3 times / day multiple, oral Recommended Dose: 120 mg, 3 times / day Route: oral Route: multiple Dose: 120 mg, 3 times / day Sources: https://www.ijmpo.org/article.asp?issn=0971-5851;year=2019;volume=40;issue=1;spage=79;epage=84;aulast=Kalaiyarasi	unhealthy, 65 Health Status: unhealthy Age Group: 65 Sex: M Sources: https://www.ijmpo.org/article.asp?issn=0971-5851;year=2019;volume=40;issue=1;spage=79;epage=84;aulast=Kalaiyarasi	Disc. AE: Toxic reaction (NOS), Toxic reaction (NOS)... AEs leading to discontinuation/dose reduction: Toxic reaction (NOS) (grade 2, 3 patients) Toxic reaction (NOS) (grade 3, 2 patients) Sources: https://www.ijmpo.org/article.asp?issn=0971-5851;year=2019;volume=40;issue=1;spage=79;epage=84;aulast=Kalaiyarasi
5.7 g 1 times / day multiple, intravenous MTD Dose: 5.7 g, 1 times / day Route: intravenous Route: multiple Dose: 5.7 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7508621/	unhealthy, 68 Health Status: unhealthy Age Group: 68 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7508621/	DLT: Nausea and vomiting, Nausea and vomiting... Dose limiting toxicities: Nausea and vomiting (grade 1, 13 patients) Nausea and vomiting (grade 2, 4 patients) Weight gain (2 patients) Edema (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/7508621/
100 mg 3 times / day multiple, oral Recommended Dose: 100 mg, 3 times / day Route: oral Route: multiple Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10761752/	unhealthy, 70 Health Status: unhealthy Age Group: 70 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/10761752/	Other AEs: Gynecomastia, Peripheral edema... Other AEs: Gynecomastia (38%) Peripheral edema (32%) Gastrointestinal discomfort (19%) Deep vein thrombosis (8%) Skin rash (5%) Hypertension (5%) Transaminases increased (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/10761752/
1104 mg 1 times / day multiple, intravenous Dose: 1104 mg, 1 times / day Route: intravenous Route: multiple Dose: 1104 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9607886/	unhealthy, 74 Health Status: unhealthy Age Group: 74 Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/9607886/	Other AEs: Nausea, Bone pain... Other AEs: Nausea (17 patients) Bone pain (17 patients) Perineal pain (1 patient) Deep vein thrombosis (4 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/9607886/
4 g 1 times / day multiple, intravenous RP2D Dose: 4 g, 1 times / day Route: intravenous Route: multiple Dose: 4 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7508621/	unhealthy Health Status: unhealthy Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/7508621/	Sources: https://pubmed.ncbi.nlm.nih.gov/7508621/

AEs

Sourcing

Vendor/Aggregator	ID	URL
A2Z Chemical	AZM13788
ABI Chem	AC1MHWYU
Aurora Fine Chemicals LLC	K16.450.167	http://online.aurorafinechemicals.com/info?ID=K16.450.167
BLD Pharm	BD131559	http://www.bldpharm.com/products/4719-75-9.html
BOC Sciences	4719-75-9	https://www.bocsci.com/tetrasodium-fosfestrol-cas-4719-75-9-item-15065.html
Changzhou Highassay Chemical Co., Ltd	my_sub1996
ChemMol	99096292	http://www.chemmol.com/chemmol/99096292.html
Glentham Life Sciences	GP2439	http://www.glentham.com/products/product/GP2439/
Hairui	HR110840	http://www.hairuichem.com/en/product/23519-26-8.html
iChemical	EBD43877	http://www.ichemical.com/chemicals/cas-4719-75-9
NovoSeek	3034148
PubChem	3034148	https://pubchem.ncbi.nlm.nih.gov/compound/3034148

PubMed

Title	Date	PubMed
Small nuclear RING finger protein expression during gonad development: regulation by gonadotropins and estrogen in the postnatal ovary.	2004-05	14749358
Abnormal morphology of the penis in male rats exposed neonatally to diethylstilbestrol is associated with altered profile of estrogen receptor-alpha protein, but not of androgen receptor protein: a developmental and immunocytochemical study.	2004-05	14749301
Upregulation of angiotensin II type 2 receptor expression in estrogen-induced pituitary hyperplasia.	2004-05	14722030
Neonatal estrogenization leads to increased expression of cellular retinol binding protein 2 in the mouse reproductive tract.	2004-04	14963765
Diethylstilbestrol induces fish oocyte maturation.	2004-03-09	14990787
Long-term alteration of gene expression without morphological change in testis after neonatal exposure to genistein in mice: toxicogenomic analysis using cDNA microarray.	2004-03	14871586
Modulation of AhR-mediated CYP1A1 mRNA and EROD activities by 17beta-estradiol and dexamethasone in TCDD-induced H411E cells.	2004-03	14691211
Dimerization modulates the activity of the orphan nuclear receptor ERRgamma.	2004-02-20	14751226
Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals.	2004-02-15	14751673
Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1.	2004-02	14605097
Age, sex and co-exposure to N-ethyl-N-nitrosourea influence mutations in the Alu repeat sequences in diethylstilbestrol-induced kidney tumors in Syrian hamsters.	2004-01	14681315
Toxicogenomic difference between diethylstilbestrol and 17beta-estradiol in mouse testicular gene expression by neonatal exposure.	2004-01	14648872
The inhibitory effects of flavonoids and antiestrogens on the Glut1 glucose transporter in human erythrocytes.	2003-12-15	14642735
The immune system of geriatric mice is modulated by estrogenic endocrine disruptors (diethylstilbestrol, alpha-zearalanol, and genistein): effects on interferon-gamma.	2003-12-15	14636701
Limb reduction defects in the first generation and deafness in the second generation of intrauterine exposed fetuses to diethylstilbestrol.	2003-12-09	14659782
Effect of diethylstilbestrol on polyamine metabolism in hamster epididymis.	2003-12	14695980
Similarities and differences in uterine gene expression patterns caused by treatment with physiological and non-physiological estrogens.	2003-12	14664709
Induction of vitellogenin synthesis in an Atlantic salmon (Salmo salar) hepatocyte culture: a sensitive in vitro bioassay for the oestrogenic and anti-oestrogenic activity of chemicals.	2003-11-07	14602523
Effects of endocrine disrupting compounds on the pathology and oestrogen receptor alpha and beta distribution in the uterus and cervix of ewe lambs.	2003-11	14652134
Combined effects of tumor promoters and serum on proliferin mRNA induction: a biomarker sensitive to saccharin, 2,3,7,8-TCDD, and other compounds at minimal concentrations promoting C3H/10T1/2 cell transformation.	2003-10-24	14514435
The effect of endocrine disrupting chemicals on thyroid hormone binding to Japanese quail transthyretin and thyroid hormone receptor.	2003-10-15	13129501
Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor.	2003-10	14565775
Neonatal diethylstilbestrol exposure induces persistent elevation of c-fos expression and hypomethylation in its exon-4 in mouse uterus.	2003-10	14502647
Autocrine/paracrine action of pituitary vasoactive intestinal peptide on lactotroph hyperplasia induced by estrogen.	2003-10	12960047
Sulfonation of environmental estrogens by zebrafish cytosolic sulfotransferases.	2003-09-12	12943655
Cirrhosis with steatohepatitis following longterm stilboestrol treatment.	2003-08	12890826
Estrogenic endocrine disruptive components interfere with calcium handling and differentiation of human trophoblast cells.	2003-07-01	12858341
Cytotoxic and xenoestrogenic effects via biotransformation of trans-anethole on isolated rat hepatocytes and cultured MCF-7 human breast cancer cells.	2003-07-01	12818366
In vitro modulation of prolactin mRNA by toxaphene and 3,3',4,4'-tetrachlorobiphenyl.	2003-07	12804517
Update on cryptorchidism: endocrine, environmental and therapeutic aspects.	2003-06	12952375
Activation of estrogen receptor alpha and ERbeta by 4-methylbenzylidene-camphor in human and rat cells: comparison with phyto- and xenoestrogens.	2003-04-30	12765243
Differential expression of c-fos and c-myc protooncogenes by estrogens, xenobiotics and other growth-stimulatory agents in primary rat hepatocytes.	2003-03	12632255
Prenatal exposure to estrogenic compounds alters the expression pattern of platelet-derived growth factor receptors alpha and beta in neonatal rat testis: identification of gonocytes as targets of estrogen exposure.	2003-03	12604637
Quantitative structure-activity relationships for estrogen receptor binding affinity of phenolic chemicals.	2003-03	12598185
Diethylstilbestrol induces rat spermatogenic cell apoptosis in vivo through increased expression of spermatogenic cell Fas/FasL system.	2003-02-21	12477725
Endocrine disrupting chemicals: interference of thyroid hormone binding to transthyretins and to thyroid hormone receptors.	2003-01-31	12581883
Long-lasting effects of lindane on mouse spermatogenesis induced by in utero exposure.	2003-01-01	12507655
Oxidative DNA damage induced by toluene is involved in its male reproductive toxicity.	2003-01	12653219
Simulation of the different biological activities of diethylstilbestrol (DES) on estrogen receptor alpha and estrogen-related receptor gamma.	2003-01	12579585
Improvement of a sensitive enzyme-linked immunosorbent assay for screening estrogen receptor binding activity.	2002-12	12463546
Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents.	2002-12	12460799
Induction of reproductive tract developmental abnormalities in the male rat by lowering androgen production or action in combination with a low dose of diethylstilbestrol: evidence for importance of the androgen-estrogen balance.	2002-12	12446607
Responsiveness of endometrial genes Connexin26, Connexin43, C3 and clusterin to primary estrogen, selective estrogen receptor modulators, phyto- and xenoestrogens.	2002-10	12370124
Modulation of the onset of postnatal development of H(+)-ATPase-rich cells by steroid hormones in rat epididymis.	2002-10	12297525
Uterine responsiveness to estradiol and DNA methylation are altered by fetal exposure to diethylstilbestrol and methoxychlor in CD-1 mice: effects of low versus high doses.	2002-08-15	12217638
Relationship between estrogen receptor-binding and estrogenic activities of environmental estrogens and suppression by flavonoids.	2002-07	12224631
Estrogen receptor binding assay of chemicals with a surface plasmon resonance biosensor.	2002-05	12127041
Effect of mesulergine on prolactin secretion and dopamine D2 receptors-adaptive changes in diethylstilbestrol-induced hyperplasia of the rat anterior pituitary.	1992-03	1421203
Induction of urogenital anomalies and some tumors in the progeny of mice receiving diethylstilbestrol during pregnancy.	1977-04	14781
Clear cell adenocarcinoma of the cervix and vagina. A clinicopathologic study of 21 cases with and without a history of maternal ingestion of estrogens.	1976-02	1253110

Patents

Sample Use Guides

In Vivo Use Guide

360-480 mg 3 times/day. Maintenance: 120-240 mg 3 times/day.

Route of Administration: Oral

In Vitro Use Guide

1–20 µg/ml

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:34:56 GMT 2025` Edited by `admin` on `Mon Mar 31 17:34:56 GMT 2025`
Record UNII	A0E0NMA80F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FOSFESTROL

Official Name

English

DIETHYLSTILBESTROL DIPHOSPHATE

Preferred Name

English

DIETHYLSTILBESTROL DIPHOSPHATE [VANDF]

Common Name

English

FOSFESTROL [MART.]

Common Name

English

FOSFESTROL [JAN]

Common Name

English

fosfestrol [INN]

Common Name

English

DIETHYLSTILBESTROL DIPHOSPHATE [ORANGE BOOK]

Common Name

English

PHENOL, 4,4'-(1,2-DIETHYL-1,2-ETHENEDIYL)BIS-, BIS(DIHYDROGEN PHOSPHATE), (E)

Common Name

English

.ALPHA.,.ALPHA.'-DIETHYL-(E)-4,4'-STILBENEDIOL BIS(DIHYDROGEN PHOSPHATE)

Common Name

English

STILPHOSTROL

Brand Name

English

FOSFESTROL [MI]

Common Name

English

Fosfestrol [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

L02AA04