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Identification
NameDiethylstilbestrol
Accession NumberDB00255  (APRD00920, EXPT01164)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
(E)-3,4-bis(4-hydroxyphenyl)-3-hexeneNot AvailableNot Available
4,4'-dihydroxy-α,β-diethylstilbeneNot AvailableNot Available
DESNot AvailableNot Available
StilboestrolNot AvailableNot Available
trans-4,4'-(1,2-diethyl-1,2-ethenediyl)bisphenolNot AvailableNot Available
trans-DiethylstilbesterolNot AvailableNot Available
trans-DiethylstilbestrolNot AvailableNot Available
trans-DiethylstilboesterolNot AvailableNot Available
α,α'-diethyl-(E)-4,4'-stilbenediolNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
DistilbeneNot Available
StilbestrolNot Available
Brand mixturesNot Available
Categories
CAS number56-53-1
WeightAverage: 268.3502
Monoisotopic: 268.146329884
Chemical FormulaC18H20O2
InChI KeyInChIKey=RGLYKWWBQGJZGM-ISLYRVAYSA-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/b18-17+
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
Mass Specshow(9.87 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassStilbenes
SubclassNot Available
Direct parentStilbenes
Alternative parentsPhenylpropenes; Phenols and Derivatives; Polyols; Polyamines; Enols
Substituentsphenylpropene; phenol derivative; benzene; polyol; polyamine; enol
Classification descriptionThis compound belongs to the stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Pharmacology
IndicationUsed 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.
PharmacodynamicsDiethylstilbestrol 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 actionEstrogens 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).
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySymptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9973
Blood Brain Barrier - 0.5559
Caco-2 permeable + 0.8264
P-glycoprotein substrate Substrate 0.5737
P-glycoprotein inhibitor I Non-inhibitor 0.6542
P-glycoprotein inhibitor II Non-inhibitor 0.8478
Renal organic cation transporter Non-inhibitor 0.8465
CYP450 2C9 substrate Non-substrate 0.8149
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.5107
CYP450 1A2 substrate Inhibitor 0.9106
CYP450 2C9 substrate Inhibitor 0.9064
CYP450 2D6 substrate Non-inhibitor 0.7017
CYP450 2C19 substrate Inhibitor 0.9198
CYP450 3A4 substrate Inhibitor 0.8361
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9488
Ames test Non AMES toxic 0.9579
Carcinogenicity Non-carcinogens 0.6772
Biodegradation Not ready biodegradable 0.9111
Rat acute toxicity 1.9462 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.6894
hERG inhibition (predictor II) Non-inhibitor 0.6408
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb
  • Eli lilly and co
  • Tablicaps inc
  • Bayer pharmaceuticals corp
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Diethylstilbestrol powder13.77USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point170.5 °CPhysProp
water solubility12 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP5.07HANSCH,C ET AL. (1995)
logS-4.35ADME Research, USCD
Predicted Properties
PropertyValueSource
water solubility1.09e-02 g/lALOGPS
logP4.62ALOGPS
logP5.19ChemAxon
logS-4.4ALOGPS
pKa (strongest acidic)9.13ChemAxon
pKa (strongest basic)-6ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count2ChemAxon
polar surface area40.46ChemAxon
rotatable bond count4ChemAxon
refractivity83.24ChemAxon
polarizability30.69ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot 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
ResourceLink
KEGG DrugD00577
KEGG CompoundC07620
PubChem Compound448537
PubChem Substance46507453
ChemSpider2946
ChEBI4531
ChEMBLCHEMBL411
Therapeutic Targets DatabaseDAP001011
PharmGKBPA449307
HETDES
Drug Product Database2100304
WikipediaDiethylstilbestrol
ATC CodesG03CB02G03CC05L02AA01
AHFS Codes
  • 68:16.04
PDB Entries
FDA labelNot Available
MSDSshow(73.1 KB)
Interactions
Drug Interactions
Drug
AmobarbitalThe enzyme inducer, amobarbital, decreases the effect of the hormone agent, diethylstilbestrol.
AprobarbitalThe enzyme inducer, aprobarbital, decreases the effect of the hormone agent, diethylstilbestrol.
ButabarbitalThe enzyme inducer, butabarbital, decreases the effect of the hormone agent, diethylstilbestrol.
ButalbitalThe enzyme inducer, butalbital, decreases the effect of the hormone agent, diethylstilbestrol.
ButethalThe enzyme inducer, butethal, decreases the effect of the hormone agent, diethylstilbestrol.
EthotoinThe enzyme inducer, ethotoin, decreases the effect of the hormone agent, diethylstilbestrol.
FosphenytoinThe enzyme inducer, fosphenytoin, may decrease the therapeutic effect of diethylstilbestrol.
GriseofulvinThe enzyme inducer, griseofulvin, decreases the effect of the hormone agent, diethylstilbestrol.
HeptabarbitalThe enzyme inducer, heptabarbital, decreases the effect of the hormone agent, diethylstilbestrol.
HexobarbitalThe enzyme inducer, hexobarbital, decreases the effect of the hormone agent, diethylstilbestrol.
MephenytoinThe enzyme inducer, mephenytoin, decreases the effect of the hormone agent, diethylstilbestrol.
MethohexitalThe enzyme inducer, methohexital, decreases the effect of the hormone agent, diethylstilbestrol.
MethylphenobarbitalThe enzyme inducer, methylphenobarbital, decreases the effect of the hormone agent, diethylstilbestrol.
PentobarbitalThe enzyme inducer, pentobarbital, decreases the effect of the hormone agent, diethylstilbestrol.
PhenobarbitalThe enzyme inducer, phenobarbital, may decrease the therapeutic effect of diethylstilbestrol.
PhenytoinThe enzyme inducer, phenytoin, decreases the effect of the hormone agent, diethylstilbestrol.
PrednisoloneThe estrogenic agent, diethylstilbestrol, may increase the effect of the corticosteroid, prednisolone.
PrednisoneThe estrogenic agent, diethylstilbestrol, may increase the effect of corticosteroid, prednisone.
PrimidoneThe enzyme inducer, primidone, may decrease the effect of the hormone agent, diethylstilbestrol.
RaloxifeneAssociation not recommended
SecobarbitalThe enzyme inducer, secobarbital, decreases the effect of the hormone agent, diethylstilbestrol.
TalbutalThe enzyme inducer, talbutal, decreases the effect of the hormone agent, diethylstilbestrol.
TipranavirDiethylstilbestrol may increase the adverse dermatological effects (i.e. skin rash) of Tipranavir. Tipranavir may decrease the serum concentration Diethylstilbestrol. Monitor estrogen levels during concomitant therapy.
Ursodeoxycholic acidEstrogens decreases the effect of ursodiol
Food InteractionsNot Available

1. Estrogen receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Estrogen receptor P03372 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Estrogen-related receptor gamma P62508 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Estrogen receptor beta Q92731 Details

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

1. Catechol O-methyltransferase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Catechol O-methyltransferase P21964 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 19A1 P11511 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2A6 P11509 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

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

1. Transthyretin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Transthyretin P02766 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

Comments
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08