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Record Information
Version3.6
Creation Date2006-05-18 08:38:06 UTC
Update Date2016-02-11 01:05:07 UTC
HMDB IDHMDB01926
Secondary Accession NumbersNone
Metabolite Identification
Common Name17a-Ethynylestradiol
DescriptionEthinyl estradiol. A semisynthetic alkylated estradiol with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in oral contraceptives. -- Pubchem; estradiol (17-beta estradiol) (also oestradiol) is a sex hormone. Labelled the "female" hormone but also present in males it represents the major estrogen in humans. Critical for sexual functioning, estradiol also supports bone growth. -- Wikipedia; One of the fascinating twists to mammalian sexual differentiation is that estradiol is one of the two active metabolites of testosterone in males (the other being dihydrotestosterone). estradiol cannot be transferred readily from the circulation into the brain. Since fetuses of both sexes are exposed to similarly high levels of maternal estradiol, it can play little role in prenatal sexual differentiation. However, testosterone enters the central nervous system more freely and significant amounts are aromatized to estradiol within the brain of most male mammals, including humans. There is now much evidence that the programming of adult male sexual behavior in "lower mammals," (such as mounting rather than lordosis behavior), is largely dependent on estradiol produced in the central nervous system during prenatal life and early infancy from testosterone. We do not yet know whether this process plays a minimal or significant part in human sexual behaviors. -- Wikipedia; A synthetic form of estradiol, called ethinyl estradiol is a major component of hormonal contraceptive devices. Combined oral contraceptives contain ethinyl estradiol and a progestin, which both contribute to the inhibition of GnRH, LH, and FSH. The inhibition of these hormones accounts for the ability of combined oral contraceptives or birth control pills to prevent ovulation and thus prevent pregnancy. Other types of hormonal birth control contain only progestins and no ethinyl estradiol. -- Wikipedia.
Structure
Thumb
Synonyms
ValueSource
17-Ethinyl-3,17-estradiolChEBI
17-Ethinyl-3,17-oestradiolChEBI
17-EthinylestradiolChEBI
17alpha-Ethinyl estradiolChEBI
Ethinyl estradiolChEBI
EthinyloestradiolChEBI
Ethynyl estradiolChEBI
17a-Ethinyl estradiolGenerator
17α-ethinyl estradiolGenerator
17-EthynylestradiolHMDB
17-Ethynylestradiol ramHMDB
17-EthynyloestradiolHMDB
17a-Ethinyl-17b-estradiolHMDB
17a-EthinylestradiolHMDB
17a-Ethynyl-17b-oestradiolHMDB
17a-Ethynylestradiol-L7bHMDB
17a-EthynyloestradiolHMDB
17a-Ethynyloestradiol-17bHMDB
AloraHMDB
AmenoronHMDB
AnovlarHMDB
Chee-O-genHMDB
Chee-O-genfHMDB
Diognat-eHMDB
Diogyn eHMDB
Diogyn-eHMDB
DyloformHMDB
ErtonylHMDB
EsclimHMDB
EsteedHMDB
EstigynHMDB
EstinylHMDB
Eston-eHMDB
EstoralHMDB
Estoral {[orion]}HMDB
EstoralsHMDB
EstringHMDB
EstrogenHMDB
EthidolHMDB
EthinoralHMDB
EthinylestriolHMDB
EthynylestradiolHMDB
EticyclinHMDB
EticyclolHMDB
EticylolHMDB
EtinestrolHMDB
EtinestrylHMDB
EtinoestrylHMDB
EtistradiolHMDB
EtivexHMDB
FeminoneHMDB
FempatchHMDB
FollicoralHMDB
GinestreneHMDB
GynodiolHMDB
GynolettHMDB
InestraHMDB
InnofemHMDB
KolpolynHMDB
LinoralHMDB
LynoralHMDB
MenolynHMDB
MenostarHMDB
neo-EstroneHMDB
Nogest-SHMDB
NovestrolHMDB
OradiolHMDB
OrestralynHMDB
OrestraylnHMDB
OvexHMDB
PalonylHMDB
PerovexHMDB
PrimogynHMDB
Primogyn CHMDB
Primogyn mHMDB
Progynon CHMDB
Progynon mHMDB
SpanestrinHMDB
Thiuram eHMDB
ThiuranideHMDB
VagifemHMDB
YlestrolHMDB
Chemical FormulaC20H24O2
Average Molecular Weight296.4034
Monoisotopic Molecular Weight296.177630012
IUPAC Name(1S,10R,11S,14R,15S)-14-ethynyl-15-methyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-2(7),3,5-triene-5,14-diol
Traditional Nameethinyl estradiol
CAS Registry Number57-63-6
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=CC=C(O)C=C3CC[C@@]21[H]
InChI Identifier
InChI=1S/C20H24O2/c1-3-20(22)11-9-18-17-6-4-13-12-14(21)5-7-15(13)16(17)8-10-19(18,20)2/h1,5,7,12,16-18,21-22H,4,6,8-11H2,2H3/t16-,17-,18+,19+,20+/m1/s1
InChI KeyInChIKey=BFPYWIDHMRZLRN-SLHNCBLASA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassEstrane steroids
Direct ParentEstrogens and derivatives
Alternative Parents
Substituents
  • Estrogen-skeleton
  • 17-hydroxysteroid
  • Hydroxysteroid
  • 3-hydroxysteroid
  • Phenanthrene
  • Tetralin
  • Benzenoid
  • Ynone
  • Tertiary alcohol
  • Cyclic alcohol
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Drug
  • Drug metabolite
Biofunction
  • Cell signaling
  • Fuel and energy storage
  • Fuel or energy source
  • Hormones, Membrane component
  • Membrane integrity/stability
  • Waste products
Application
  • Nutrients
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Extracellular
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point183 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0113 mg/mL at 27 °CNot Available
LogP3.67HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0068 mg/mLALOGPS
logP3.63ALOGPS
logP3.9ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)10.33ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity87.37 m3·mol-1ChemAxon
Polarizability34.53 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000b-0290000000-0ef72fb5e00440b9ff50View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-000i-0960000000-945d82a0ab94f246ac88View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-056s-2910000000-0d38daebb87a39304e91View in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80) , Positivesplash10-03di-0890000000-7a166e952207cf7bc1d3View in MoNA
MSMass Spectrum (Electron Ionization)splash10-03dj-2980000000-831c8190c59f98fc8623View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Adipose Tissue
  • Adrenal Cortex
  • Adrenal Gland
  • Bladder
  • Brain
  • Epidermis
  • Fibroblasts
  • Gonads
  • Intestine
  • Kidney
  • Liver
  • Muscle
  • Nerve Cells
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Spleen
  • Stratum Corneum
  • Testes
  • Thyroid Gland
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.00016 (0.000084-0.00027) uMAdult (>18 years old)BothNormal details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableNormal
  • Not Applicable
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Prostate cancer
details
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00977
DrugBank Metabolite IDDBMET00538
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB003598
KNApSAcK IDNot Available
Chemspider ID5770
KEGG Compound IDC07534
BioCyc ID--ABIETADIENE
BiGG IDNot Available
Wikipedia LinkAlora
NuGOwiki LinkHMDB01926
Metagene LinkHMDB01926
METLIN ID6392
PubChem Compound5991
PDB IDNot Available
ChEBI ID4903
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Kaufer D, Ogle WO, Pincus ZS, Clark KL, Nicholas AC, Dinkel KM, Dumas TC, Ferguson D, Lee AL, Winters MA, Sapolsky RM: Restructuring the neuronal stress response with anti-glucocorticoid gene delivery. Nat Neurosci. 2004 Sep;7(9):947-53. Epub 2004 Aug 8. [15300253 ]
  2. Czernik PJ, Little JM, Barone GW, Raufman JP, Radominska-Pandya A: Glucuronidation of estrogens and retinoic acid and expression of UDP-glucuronosyltransferase 2B7 in human intestinal mucosa. Drug Metab Dispos. 2000 Oct;28(10):1210-6. [10997942 ]
  3. Stabile LP, Davis AL, Gubish CT, Hopkins TM, Luketich JD, Christie N, Finkelstein S, Siegfried JM: Human non-small cell lung tumors and cells derived from normal lung express both estrogen receptor alpha and beta and show biological responses to estrogen. Cancer Res. 2002 Apr 1;62(7):2141-50. [11929836 ]
  4. Li X, Strauss L, Kaatrasalo A, Mayerhofer A, Huhtaniemi I, Santti R, Makela S, Poutanen M: Transgenic mice expressing p450 aromatase as a model for male infertility associated with chronic inflammation in the testis. Endocrinology. 2006 Mar;147(3):1271-7. Epub 2005 Nov 23. [16306085 ]
  5. Wernert N: [Immunohistochemistry of the prostate and prostate carcinomas] Veroff Pathol. 1991;135:1-163. [2038892 ]
  6. Zhang L, Sukhareva M, Barker JL, Maric D, Hao Y, Chang YH, Ma W, O'Shaughnessy T, Rubinow DR: Direct binding of estradiol enhances Slack (sequence like a calcium-activated potassium channel) channels' activity. Neuroscience. 2005;131(2):275-82. [15708472 ]
  7. Herrero P, Soto PF, Dence CS, Kisrieva-Ware Z, Delano DA, Peterson LR, Gropler RJ: Impact of hormone replacement on myocardial fatty acid metabolism: potential role of estrogen. J Nucl Cardiol. 2005 Sep-Oct;12(5):574-81. [16171718 ]
  8. Shah MG, Maibach HI: Estrogen and skin. An overview. Am J Clin Dermatol. 2001;2(3):143-50. [11705091 ]
  9. Safi R, Kovacic A, Gaillard S, Murata Y, Simpson ER, McDonnell DP, Clyne CD: Coactivation of liver receptor homologue-1 by peroxisome proliferator-activated receptor gamma coactivator-1alpha on aromatase promoter II and its inhibition by activated retinoid X receptor suggest a novel target for breast-specific antiestrogen therapy. Cancer Res. 2005 Dec 15;65(24):11762-70. [16357189 ]
  10. vom Saal FS, Grant WM, McMullen CW, Laves KS: High fetal estrogen concentrations: correlation with increased adult sexual activity and decreased aggression in male mice. Science. 1983 Jun 17;220(4603):1306-9. [6857252 ]
  11. Schmitt PM, Gohil K, Kaufman MP: Spinal estrogen attenuates the exercise pressor reflex but has little effect on the expression of genes regulating neurotransmitters in the dorsal root ganglia. J Appl Physiol. 2006 Mar;100(3):958-64. Epub 2005 Nov 23. [16306253 ]
  12. Kalaitzidis D, Ok J, Sulak L 2nd, Starczynowski DT, Gilmore TD: Characterization of a human REL-estrogen receptor fusion protein with a reverse conditional transforming activity in chicken spleen cells. Oncogene. 2004 Sep 30;23(45):7580-7. [15326488 ]
  13. Pierard-Franchimont C, Letawe C, Goffin V, Pierard GE: Skin water-holding capacity and transdermal estrogen therapy for menopause: a pilot study. Maturitas. 1995 Sep;22(2):151-4. [8538484 ]
  14. de la Monte SM, Moore GW, Hutchins GM: Metastatic behavior of prostate cancer. Cluster analysis of patterns with respect to estrogen treatment. Cancer. 1986 Aug 15;58(4):985-93. [3719562 ]
  15. Harris H, Henderson R, Bhat R, Komm B: Regulation of metallothionein II messenger ribonucleic acid measures exogenous estrogen receptor-beta activity in SAOS-2 and LNCaPLN3 cells. Endocrinology. 2001 Feb;142(2):645-52. [11159835 ]
  16. Frolich A, Christensen L, Andersen J: Estrogen receptors appear undetectable in the C-cells of the human thyroid gland. Bone. 1990;11(6):393-6. [1706609 ]
  17. Siiteri PK: Review of studies on estrogen biosynthesis in the human. Cancer Res. 1982 Aug;42(8 Suppl):3269s-3273s. [7083184 ]
  18. Koehler KF, Helguero LA, Haldosen LA, Warner M, Gustafsson JA: Reflections on the discovery and significance of estrogen receptor beta. Endocr Rev. 2005 May;26(3):465-78. Epub 2005 Apr 27. [15857973 ]
  19. Moro L, Reineri S, Piranda D, Pietrapiana D, Lova P, Bertoni A, Graziani A, Defilippi P, Canobbio I, Torti M, Sinigaglia F: Nongenomic effects of 17beta-estradiol in human platelets: potentiation of thrombin-induced aggregation through estrogen receptor beta and Src kinase. Blood. 2005 Jan 1;105(1):115-21. Epub 2004 Jun 15. [15198955 ]
  20. Nakano Y, Oshima T, Ozono R, Ueda A, Oue Y, Matsuura H, Sanada M, Ohama K, Chayama K, Kambe M: Estrogen replacement suppresses function of thrombin stimulated platelets by inhibiting Ca(2+) influx and raising cyclic adenosine monophosphate. Cardiovasc Res. 2002 Feb 15;53(3):634-41. [11861034 ]
  21. FDA label.

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Wang B, Sanchez RI, Franklin RB, Evans DC, Huskey SE: The involvement of CYP3A4 and CYP2C9 in the metabolism of 17 alpha-ethinylestradiol. Drug Metab Dispos. 2004 Nov;32(11):1209-12. Epub 2004 Aug 10. [15304426 ]
General function:
Involved in monooxygenase activity
Specific function:
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).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
References
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [15601807 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular weight:
49761.2
References
  1. Xue Y, Moore LB, Orans J, Peng L, Bencharit S, Kliewer SA, Redinbo MR: Crystal structure of the pregnane X receptor-estradiol complex provides insights into endobiotic recognition. Mol Endocrinol. 2007 May;21(5):1028-38. Epub 2007 Feb 27. [17327420 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
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. Can activate the transcriptional activity of TFF1
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular weight:
66215.4
References
  1. Micevych PE, Chaban V, Ogi J, Dewing P, Lu JK, Sinchak K: Estradiol stimulates progesterone synthesis in hypothalamic astrocyte cultures. Endocrinology. 2007 Feb;148(2):782-9. Epub 2006 Nov 9. [17095591 ]
  2. Garcia-Segura LM, Sanz A, Mendez P: Cross-Talk between IGF-I and Estradiol in the Brain: Focus on Neuroprotection. Neuroendocrinology. 2006 Nov 23;. [17124377 ]
  3. Brama M, Gnessi L, Basciani S, Cerulli N, Politi L, Spera G, Mariani S, Cherubini S, d'Abusco AS, Scandurra R, Migliaccio S: Cadmium induces mitogenic signaling in breast cancer cell by an ERalpha-dependent mechanism. Mol Cell Endocrinol. 2007 Jan 29;264(1-2):102-8. Epub 2006 Nov 27. [17125913 ]
  4. Lehnes K, Winder AD, Alfonso C, Kasid N, Simoneaux M, Summe H, Morgan E, Iann MC, Duncan J, Eagan M, Tavaluc R, Evans CH Jr, Russell R, Wang A, Hu F, Stoica A: THE EFFECT OF ESTRADIOL ON IN VIVO TUMORIGENESIS IS MODULATED BY THE ErbB2/PI 3-K/Akt1 PATHWAY. Endocrinology. 2006 Nov 30;. [17138652 ]
  5. Mukai H, Tsurugizawa T, Ogiue-Ikeda M, Murakami G, Hojo Y, Ishii H, Kimoto T, Kawato S: Local neurosteroid production in the hippocampus: influence on synaptic plasticity of memory. Neuroendocrinology. 2006;84(4):255-63. Epub 2006 Dec 1. [17142999 ]
  6. Notch EG, Mayer GD: 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8. Epub 2009 Jan 23. [19237207 ]
  7. Bennink HJ: Reprint of Are all estrogens the same? Maturitas. 2008 Sep-Oct;61(1-2):195-201. [19434891 ]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular weight:
174205.6
References
  1. Kauffmann HM, Schrenk D: Sequence analysis and functional characterization of the 5'-flanking region of the rat multidrug resistance protein 2 (mrp2) gene. Biochem Biophys Res Commun. 1998 Apr 17;245(2):325-31. [9571149 ]
  2. Trauner M, Arrese M, Soroka CJ, Ananthanarayanan M, Koeppel TA, Schlosser SF, Suchy FJ, Keppler D, Boyer JL: The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis. Gastroenterology. 1997 Jul;113(1):255-64. [9207286 ]
General function:
Involved in ATP binding
Specific function:
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes
Gene Name:
ABCB11
Uniprot ID:
O95342
Molecular weight:
146405.8
References
  1. Lee JM, Trauner M, Soroka CJ, Stieger B, Meier PJ, Boyer JL: Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology. 2000 Jan;118(1):163-72. [10611165 ]
  2. Huang L, Smit JW, Meijer DK, Vore M: Mrp2 is essential for estradiol-17beta(beta-D-glucuronide)-induced cholestasis in rats. Hepatology. 2000 Jul;32(1):66-72. [10869290 ]
General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Kim WY, Benet LZ: P-glycoprotein (P-gp/MDR1)-mediated efflux of sex-steroid hormones and modulation of P-gp expression in vitro. Pharm Res. 2004 Jul;21(7):1284-93. [15290871 ]
General function:
Involved in bile acid:sodium symporter activity
Specific function:
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presence of sodium.
Gene Name:
SLC10A1
Uniprot ID:
Q14973
Molecular weight:
38118.64
References
  1. Lee JM, Trauner M, Soroka CJ, Stieger B, Meier PJ, Boyer JL: Expression of the bile salt export pump is maintained after chronic cholestasis in the rat. Gastroenterology. 2000 Jan;118(1):163-72. [10611165 ]