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Identification
Name Diethylstilbestrol
Accession Number DB00255 (APRD00920, EXPT01164)
Type small molecule
Groups approved
Description

A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • DEB
  • DES
  • Diethylstilbesterol
  • Diethylstilbestrol BP
  • Diethylstilboesterol
  • Dietilestilbestrol
  • Percutatrine oestrogenique iscovesco
  • Rcra waste number U089
  • trans-Diethylstilbesterol
  • trans-Diethylstilbestrol
  • trans-Diethylstilboesterol
Brand names
  • Acnestrol
  • Agostilben
  • Antigestil
  • Bio-des
  • Bufon
  • Climaterine
  • Comestrol
  • Comestrol estrobene
  • Cyren
  • Cyren A
  • Dawe's destrol
  • Desma
  • Destrol
  • Di-Estryl
  • Diastyl
  • Dibestrol
  • DiBestrol 2 Premix
  • Dicorvin
  • Distilbene
  • Domestrol
  • Dyestrol
  • Estilben
  • Estilbin MCO
  • Estril
  • Estrobene
  • Estrogenine
  • Estromenin
  • Estrosyn
  • Follidiene
  • Fonatol
  • Grafestrol
  • Gynopharm
  • Hi-Bestrol
  • Idroestril
  • Iscovesco
  • Makarol
  • Menostilbeen
  • Micrest
  • Microest
  • Milestrol
  • neo-Oestranol 1
  • Neo-Oestranol I
  • New-Estranol 1
  • OeKolp
  • Oestrogenine
  • Oestrol vetag
  • Oestromenin
  • Oestromensil
  • Oestromensyl
  • Oestromienin
  • Oestromon
  • Pabestrol
  • Palestrol
  • Protectona
  • Rumestrol 1
  • Rumestrol 2
  • Sedestran
  • Serral
  • Sexocretin
  • Sibol
  • Sintestrol
  • Stibilium
  • Stil
  • Stil-Rol
  • Stilbestroform
  • Stilbestrol
  • Stilbestrone
  • Stilbetin
  • Stilboefral
  • Stilboestroform
  • Stilboestrol
  • Stilbofolin
  • Stilbofollin
  • Stilbol
  • Stilkap
  • Stilphostrol
  • strobene
  • Synestrin
  • Synthestrin
  • Synthoestrin
  • Synthofolin
  • Syntofolin
  • Tampovagan stilboestrol
  • Tylosterone
  • Vagestrol
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents, Hormonal
  • Carcinogens
  • Estrogens, Non-Steroidal
CAS number 56-53-1
Weight Average: 268.3502
Monoisotopic: 268.146329884
Chemical Formula C18H20O2
InChI Key InChIKey=RGLYKWWBQGJZGM-UHFFFAOYSA-N
InChI
InChI=1S/C18H20O2/c1-3-17(13-5-9-15(19)10-6-13)18(4-2)14-7-11-16(20)12-8-14/h5-12,19-20H,3-4H2,1-2H3
Plain Text
IUPAC Name
4-[4-(4-hydroxyphenyl)hex-3-en-3-yl]phenol
SMILES
CCC(=C(CC)C1=CC=C(O)C=C1)C1=CC=C(O)C=C1
Plain Text
Mass Spec show (9.9 KB)
Taxonomy
Kingdom Not Available
Classes
  • Stilbenes
Substructures
  • Stilbenes
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Phenols and Derivatives
  • Phenylpropenes
  • Benzene and Derivatives
  • Isoprenes
  • Aromatic compounds
  • Styrene Derivatives
  • Phenyl Esters
Pharmacology
Indication Used in the treatment of prostate cancer. Previously used in the prevention of miscarriage or premature delivery in pregnant women prone to miscarriage or premature delivery.
Pharmacodynamics Diethylstilbestrol is a synthetic estrogen that was developed to supplement a woman's natural estrogen production. In 1971, the Food and Drug Administration (FDA) issued a Drug Bulletin advising physicians to stop prescribing DES to pregnant women because it was linked to a rare vaginal cancer in female offspring.
Mechanism of action Estrogens diffuse into their target cells and interact with a protein receptor, the estrogen receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. The effect of Estrogen binding their receptors causes downstream increases the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Hepatic.
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Symptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb
  • Eli lilly and co
  • Tablicaps inc
  • Bayer pharmaceuticals corp
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Diethylstilbestrol powder 13.77 USD g
Patents Not Available
Properties
State solid
Melting point 170.5 oC
Experimental Properties
Property Value Source
water solubility 0.012 mg/mL at 25 oC [YALKOWSKY,SH & DANNENFELSER,RM (1992)] PhysProp
logP 5.07 [HANSCH,C ET AL. (1995)] PhysProp
logS -4.35 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 1.09e-02 g/l ALOGPS
logP 4.62 ALOGPS
logP 5.19 ChemAxon Molconvert
logS -4.39 ALOGPS
pKa 9.73 ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 40.46 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 83.24 ChemAxon Molconvert
polarizability 30.69 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. : Leuprolide versus diethylstilbestrol for metastatic prostate cancer. The Leuprolide Study Group. N Engl J Med. 1984 Nov 15;311(20):1281-6. Pubmed
  2. DIECKMANN WJ, DAVIS ME, RYNKIEWICZ LM, POTTINGER RE: Does the administration of diethylstilbestrol during pregnancy have therapeutic value? Am J Obstet Gynecol. 1953 Nov;66(5):1062-81. Pubmed
  3. Ingle JN, Ahmann DL, Green SJ, Edmonson JH, Bisel HF, Kvols LK, Nichols WC, Creagan ET, Hahn RG, Rubin J, Frytak S: Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N Engl J Med. 1981 Jan 1;304(1):16-21. Pubmed
  4. Kuchera LK: Postcoital contraception with diethylstilbestrol. JAMA. 1971 Oct 25;218(4):562-3. Pubmed
  5. Herbst AL, Ulfelder H, Poskanzer DC: Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971 Apr 15;284(15):878-81. Pubmed
External Links
Resource Link
KEGG Drug D00577 Link_out
KEGG Compound C07620 Link_out
PubChem Compound 448537 Link_out
PubChem Substance 46507453 Link_out
ChemSpider 2946 Link_out
ChEBI 4531 Link_out
ChEMBL 4531 Link_out
Therapeutic Targets Database DAP001011 Link_out
PharmGKB PA449307 Link_out
HET DES Link_out
Drug Product Database 2100304 Link_out
Wikipedia http://en.wikipedia.org/wiki/Diethylstilbestrol Link_out
ATC Codes
  • G03CB02
  • G03CC05
  • L02AA01
AHFS Codes
  • 68:16.04
PDB Entries
FDA label Not Available
MSDS show (73.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Estrogen receptor

Pharmacological action: yes
Actions: agonist

Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues

Organism class: human
UniProt ID: P03372 Link_out
Gene: ESR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Munoz G, Ovilo C, Estelle J, Silio L, Fernandez A, Rodriguez C: Association with litter size of new polymorphisms on ESR1 and ESR2 genes in a Chinese-European pig line. Genet Sel Evol. 2007 Mar-Apr;39(2):195-206. Epub 2007 Feb 17. Pubmed
  2. Dixon A, Wells CC, Singh S, Babayan R, Maric C: Renoprotective effects of a selective estrogen receptor modulator, raloxifene, in an animal model of diabetic nephropathy. Am J Nephrol. 2007;27(2):120-8. Epub 2007 Feb 15. Pubmed
  3. Hart SA, Snyder MA, Smejkalova T, Woolley CS: Estrogen mobilizes a subset of estrogen receptor-alpha-immunoreactive vesicles in inhibitory presynaptic boutons in hippocampal CA1. J Neurosci. 2007 Feb 21;27(8):2102-11. Pubmed
  4. Baron S, Escande A, Alberola G, Bystricky K, Balaguer P, Richard-Foy H: Estrogen receptor alpha and the activating protein-1 complex cooperate during insulin-like growth factor-I-induced transcriptional activation of the pS2/TFF1 gene. J Biol Chem. 2007 Apr 20;282(16):11732-41. Epub 2007 Feb 22. Pubmed
  5. Bains M, Cousins JC, Roberts JL: Neuroprotection by estrogen against MPP+-induced dopamine neuron death is mediated by ERalpha in primary cultures of mouse mesencephalon. Exp Neurol. 2007 Apr;204(2):767-76. Epub 2007 Jan 25. Pubmed
  6. Kwok KC, Cheung NH: Measuring binding kinetics of ligands with tethered receptors by fluorescence polarization and total internal reflection fluorescence. Anal Chem. 2010 May 1;82(9):3819-25. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Estrogen-related receptor gamma

Pharmacological action: yes
Actions: agonist

Orphan receptor. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements

Organism class: human
UniProt ID: P62508 Link_out
Gene: ESRRG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Greschik H, Flaig R, Renaud JP, Moras D: Structural basis for the deactivation of the estrogen-related receptor gamma by diethylstilbestrol or 4-hydroxytamoxifen and determinants of selectivity. J Biol Chem. 2004 Aug 6;279(32):33639-46. Epub 2004 May 24. Pubmed
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

3. Estrogen receptor beta

Pharmacological action: yes
Actions: agonist

Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner. Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA- binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual

Organism class: human
UniProt ID: Q92731 Link_out
Gene: ESR2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Final amended report on the safety assessment of Methylparaben, Ethylparaben, Propylparaben, Isopropylparaben, Butylparaben, Isobutylparaben, and Benzylparaben as used in cosmetic products. Int J Toxicol. 2008;27 Suppl 4:1-82. Pubmed
  2. Geistlinger TR, McReynolds AC, Guy RK: Ligand-selective inhibition of the interaction of steroid receptor coactivators and estrogen receptor isoforms. Chem Biol. 2004 Feb;11(2):273-81. Pubmed
Enzymes

1. Catechol O-methyltransferase

Actions: substrate

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol

UniProt ID: P21964 Link_out
Gene: COMT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Engel LL, Weidenfield J, Merriam GR: Metabolism of diethylstilbestrol by rat liver: a preliminary report. J Toxicol Environ Health Suppl. 1976;1:37-44. Pubmed

2. Cytochrome P450 19A1

Actions: inducer

Catalyzes the formation of aromatic C18 estrogens from C19 androgens

UniProt ID: P11511 Link_out
Gene: CYP19A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2A6

Actions: inhibitor

Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase

UniProt ID: P11509 Link_out
Gene: CYP2A6
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. Pubmed

4. Cytochrome P450 3A4

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. Pubmed

5. Cytochrome P450 2C8

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. Pubmed

6. Cytochrome P450 2C9

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. Pubmed

7. Cytochrome P450 2E1

Actions: inhibitor

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Qu YQ, Fang ZZ, Yang L, Gao ZM, Liang R, Zhu LL, Dong PP, Zhang YY, Ge GB, Wang LM: Reversible inhibition of four important human liver cytochrome P450 enzymes by diethylstilbestrol. Pharmazie. 2011 Mar;66(3):216-21. Pubmed
Transporters

1. ATP-binding cassette sub-family G member 2

Actions: inhibitor

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sugimoto Y, Tsukahara S, Imai Y, Sugimoto Y, Ueda K, Tsuruo T: Reversal of breast cancer resistance protein-mediated drug resistance by estrogen antagonists and agonists. Mol Cancer Ther. 2003 Jan;2(1):105-12. Pubmed

2. Multidrug resistance protein 1

Actions: substrate

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Rao US, Fine RL, Scarborough GA: Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92. Pubmed
Carriers

1. Transthyretin

Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain

UniProt ID: P02766 Link_out
Gene: TTR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out
Comments
Drug created on June 13, 2005 07:24 / Updated on July 25, 2011 19:13

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.