FOSFESTROL DISODIUM

US Previously Marketed

First approved in 1941

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H18O8P2.2Na.2H
Molecular Weight	472.2737
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H+].[H+].[Na+].[Na+].CC\C(=C(\CC)C1=CC=C(OP([O-])([O-])=O)C=C1)C2=CC=C(OP([O-])([O-])=O)C=C2

InChI

InChIKey=OPZDSBAHQHNXRQ-QIKYXUGXSA-L

InChI=1S/C18H22O8P2.2Na/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);;/q;2*+1/p-2/b18-17+;;

HIDE SMILES / InChI

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 127 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22294742	Agonist 2678	0.18 nM [EC50]
Estrogen receptor beta 110 Target ID: CHEMBL242 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22294742	Agonist 2678	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 80	10.0 µM [EC50]
Estrogen-related receptor beta 8 Target ID: CHEMBL3751 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11447273	Inverse Agonist 80	700.0 nM [EC50]
Estrogen-related receptor gamma 11 Target ID: CHEMBL4245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11447273	Inverse Agonist 80	700.0 nM [EC50]
estrogen receptor 1 5 Target ID: P03372 Gene Symbol: ESR1 Sources: http://www.drugbank.ca/drugs/DB00255	Agonist 2678
estrogen-related receptor alpha 5 Target ID: P11474 Gene Symbol: ESRRA Sources: http://genesdev.cshlp.org/content/15/7/833.full	Inverse Agonist 80	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 80	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 80	1.0 µM [IC50]
estrogen receptor 2 (ER beta) 5 Target ID: Q92731 Gene Symbol: ESR2 Sources: http://www.drugbank.ca/drugs/DB00255	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Prostate cancer 178 Sources: http://www.drugbank.ca/drugs/DB00255	Primary	Approved 8429	Stilphostrol Approved Use Unknown Launch Date 1981
Prostate cancer 178 Sources: https://www.drugs.com/mmx/stilbestrol.html	Primary	Approved 8429	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 8429	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 8429	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 8429	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 8429	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 8429	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 8429	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 8429	STILBESTROL Approved Use Drug is indicated for the prevention of osteoporosis. Launch Date 1973

Doses

Dose	Population	Adverse events
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 n = 17 Health Status: unhealthy Condition: prostate cancer Age Group: 56-87 Sex: M Population Size: 17 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 n = 1 Health Status: unhealthy Condition: prostate cancer Age Group: 59 Sex: M Population Size: 1 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 n = 47 Health Status: unhealthy Condition: prostate cancer Age Group: 65 Sex: M Population Size: 47 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 Co-administed with:: SALICYLIC ACID(200 mg; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/7508621/	unhealthy, 68 n = 21 Health Status: unhealthy Condition: prostate cancer Age Group: 68 Sex: M Population Size: 21 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 n = 38 Health Status: unhealthy Condition: prostate cancer Age Group: 70 Sex: M Population Size: 38 Sources: https://pubmed.ncbi.nlm.nih.gov/10761752/	Other AEs: Hypertension, Gynecomastia... Other AEs: Hypertension (5%) Gynecomastia (38%) Peripheral edema (32%) Gastrointestinal discomfort (19%) Deep vein thrombosis (8%) Skin rash (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 Co-administed with:: MEPERIDINE(75 mg; i.m; 1/day) PROCHLORPERAZINE(12.5 mg; i.m; 1/day) Sources: https://pubmed.ncbi.nlm.nih.gov/9607886/	unhealthy, 74 n = 17 Health Status: unhealthy Condition: prostate cancer Age Group: 74 Sex: M Population Size: 17 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 Condition: prostate cancer 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
NovoSeek	3034148
PubChem	3034148	https://pubchem.ncbi.nlm.nih.gov/compound/3034148
iChemical	EBD43877	http://www.ichemical.com/chemicals/cas-4719-75-9

PubMed

Title	Date	PubMed
Follow-up study of male and female offspring of DES-treated mothers a preliminary report.	1975 Jul	1171234
The choice of estrogen preparations in the treatment of prostatic cancer.	1975 Nov 8	1182631
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 Feb	1253110
Induction of urogenital anomalies and some tumors in the progeny of mice receiving diethylstilbestrol during pregnancy.	1977 Apr	14781
Effect of mesulergine on prolactin secretion and dopamine D2 receptors-adaptive changes in diethylstilbestrol-induced hyperplasia of the rat anterior pituitary.	1992 Mar	1421203
The role of diethylstilbestrol in the treatment of prostate cancer.	2001 Aug	11502463
Increased exocytosis of secretory granules in contrast to reduced serum hormone levels in pituitary adenomas of humans and rats treated with dopamine agonist.	2001 Jun	11685661
Metabolism of bisphenol A in isolated rat hepatocytes and oestrogenic activity of a hydroxylated metabolite in MCF-7 human breast cancer cells.	2001 Mar	11465389
Modulation by estrogens and xenoestrogens of recombinant human neuronal nicotinic receptors.	2001 Nov 2	11711029
Effects of prenatal exposure to low doses of diethylstilbestrol, o,p'DDT, and methoxychlor on postnatal growth and neurobehavioral development in male and female mice.	2001 Sep	11534990
Comparison of an array of in vitro assays for the assessment of the estrogenic potential of natural and synthetic estrogens, phytoestrogens and xenoestrogens.	2001 Sep 14	11518614
Transcriptional regulation of the estrogen-inducible pS2 breast cancer marker gene by the ERR family of orphan nuclear receptors.	2001 Sep 15	11559547
Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents.	2002 Dec	12460799
Findings in female offspring of women exposed in utero to diethylstilbestrol.	2002 Feb	11814496
Interaction of estrogen mimics, singly and in combination, with plasma sex steroid-binding proteins in rainbow trout (Oncorhynchus mykiss).	2002 Feb	11792437
Metabolism of 2-hydroxy-4-methoxybenzophenone in isolated rat hepatocytes and xenoestrogenic effects of its metabolites on MCF-7 human breast cancer cells.	2002 Feb 20	11823001
Characterization of diethylstilbestrol-induced hypospadias in female mice.	2002 Jan 1	11748570
Relationship between estrogen receptor-binding and estrogenic activities of environmental estrogens and suppression by flavonoids.	2002 Jul	12224631
Estrogen mimics bind with similar affinity and specificity to the hepatic estrogen receptor in Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss).	2002 Mar	11944962
Modulation of the onset of postnatal development of H(+)-ATPase-rich cells by steroid hormones in rat epididymis.	2002 Oct	12297525
Activation of estrogen receptor alpha and ERbeta by 4-methylbenzylidene-camphor in human and rat cells: comparison with phyto- and xenoestrogens.	2003 Apr 30	12765243
Cirrhosis with steatohepatitis following longterm stilboestrol treatment.	2003 Aug	12890826
Effect of diethylstilbestrol on polyamine metabolism in hamster epididymis.	2003 Dec	14695980
Similarities and differences in uterine gene expression patterns caused by treatment with physiological and non-physiological estrogens.	2003 Dec	14664709
Oxidative DNA damage induced by toluene is involved in its male reproductive toxicity.	2003 Jan	12653219
Simulation of the different biological activities of diethylstilbestrol (DES) on estrogen receptor alpha and estrogen-related receptor gamma.	2003 Jan	12579585
Endocrine disrupting chemicals: interference of thyroid hormone binding to transthyretins and to thyroid hormone receptors.	2003 Jan 31	12581883
Long-lasting effects of lindane on mouse spermatogenesis induced by in utero exposure.	2003 Jan-Feb	12507655
In vitro modulation of prolactin mRNA by toxaphene and 3,3',4,4'-tetrachlorobiphenyl.	2003 Jul	12804517
Cytotoxic and xenoestrogenic effects via biotransformation of trans-anethole on isolated rat hepatocytes and cultured MCF-7 human breast cancer cells.	2003 Jul 1	12818366
Update on cryptorchidism: endocrine, environmental and therapeutic aspects.	2003 Jun	12952375
Differential expression of c-fos and c-myc protooncogenes by estrogens, xenobiotics and other growth-stimulatory agents in primary rat hepatocytes.	2003 Mar	12632255
Quantitative structure-activity relationships for estrogen receptor binding affinity of phenolic chemicals.	2003 Mar	12598185
Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor.	2003 Oct	14565775
Neonatal diethylstilbestrol exposure induces persistent elevation of c-fos expression and hypomethylation in its exon-4 in mouse uterus.	2003 Oct	14502647
Autocrine/paracrine action of pituitary vasoactive intestinal peptide on lactotroph hyperplasia induced by estrogen.	2003 Oct	12960047
The effect of endocrine disrupting chemicals on thyroid hormone binding to Japanese quail transthyretin and thyroid hormone receptor.	2003 Oct 15	13129501
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 Oct 24	14514435
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 Sep-Oct	14602523
Neonatal estrogenization leads to increased expression of cellular retinol binding protein 2 in the mouse reproductive tract.	2004 Apr	14963765
Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1.	2004 Feb	14605097
Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals.	2004 Feb 15	14751673
Dimerization modulates the activity of the orphan nuclear receptor ERRgamma.	2004 Feb 20	14751226
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 Jan	14681315
Long-term alteration of gene expression without morphological change in testis after neonatal exposure to genistein in mice: toxicogenomic analysis using cDNA microarray.	2004 Mar	14871586
Modulation of AhR-mediated CYP1A1 mRNA and EROD activities by 17beta-estradiol and dexamethasone in TCDD-induced H411E cells.	2004 Mar	14691211
Diethylstilbestrol induces fish oocyte maturation.	2004 Mar 9	14990787
Small nuclear RING finger protein expression during gonad development: regulation by gonadotropins and estrogen in the postnatal ovary.	2004 May	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 May	14749301
Upregulation of angiotensin II type 2 receptor expression in estrogen-induced pituitary hyperplasia.	2004 May	14722030

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

Name

Type

Language

FOSFESTROL DISODIUM

Common Name

English

FOSFESTROL DISODIUM SALT

Common Name

English

FOSFESTROL DISODIUM SALT [MI]

Common Name

English

NSC-10481

Code

English

DIETHYLSTILBESTROL 4,4'-DIPHOSPHORIC ESTER, DISODIUM SALT

Common Name

English

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

Common Name

English

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

Common Name

English

Code System Code Type Description

CAS

5965-09-3