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Identification
Name Ethinyl Estradiol
Accession Number DB00977 (APRD00691)
Type small molecule
Groups approved
Description

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]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • 17 alpha-Ethinylestradiol
  • 17 alpha-Ethynylestradiol
  • 17 alpha-Ethynyloestradiol
  • Aethinyloestradiolum
  • Aethinyoestradiol [German]
  • EE
  • EO
  • Ethinyl-Oestranol
  • Ethinylestradiolum [INN-Latin]
  • Ethinylestriol
  • Ethinyloestradiol
  • Ethynyl estradiol
  • Ethynylestradiol
  • Ethynyloestradiol
  • Etinilestradiol [INN-Spanish]
Brand names
  • Amenoron
  • Amenorone
  • Anovlar
  • Cyclosa
  • Dicromil
  • Diognat-E
  • Diogyn E
  • Diogyn-E
  • Diprol
  • Dyloform
  • Ertonyl
  • Esteed
  • Estigyn
  • Eston-E
  • Estopherol
  • Estoral
  • Estorals
  • Ethidol
  • Ethinoral
  • Ethy 11
  • Eticyclin
  • Eticyclol
  • Eticylol
  • Etinestrol
  • Etinestryl
  • Etinoestryl
  • Etistradiol
  • Etivex
  • Follicoral
  • Ginestrene
  • Gynolett
  • Halodrin
  • Inestra
  • Kolpolyn
  • Linoral
  • Marvelon
  • Menolyn
  • Mercilon
  • Microfollin
  • Neo-Estrone
  • Nogest-S
  • Novestrol
  • Oradiol
  • Orestralyn
  • Orestrayln
  • Ortho-Cyclen
  • Oviol
  • Primogyn
  • Primogyn C
  • Primogyn M
  • Progynon C
  • Progynon M
  • Prosexol
  • Spanestrin
  • Varnoline
  • Ylestrol
Brand name mixtures
  • Alesse 21 Tablets (Ethinyl Estradiol + Levonorgestrel)
  • Alesse 28 Tablets (Ethinyl Estradiol + Levonorgestrel)
  • Brevicon (Ethinyl Estradiol + Norethindrone)
  • Cyclen (Ethinyl Estradiol + Norgestimate)
  • Demulen 30 (Ethinyl Estradiol + Ethynodiol Diacetate)
  • Demulen 50 (Ethinyl Estradiol + Ethynodiol Diacetate)
  • Diane-35 (Cyproterone Acetate + Ethinyl Estradiol)
  • Evra (Ethinyl Estradiol + Norelgestromin)
  • Femhrt 1/5 (Ethinyl Estradiol + Norethindrone Acetate)
  • Geri Bons Tab (Calcium (Calcium Phosphate (Dibasic)) + Copper + Dl-Methionine + Ethinyl Estradiol + Fatty Acids + Folic Acid + Iodine + Iron Peptonized + Magnesium + Manganese + Methyltestosterone + Nicotinamide + Phosphorus (Calcium Phosphate (Dibasic)) + Pyridoxine Hydrochloride + Thiamine Hydrochloride + Thyroid + Vitamin a + Vitamin B12 + Vitamin B2 + Vitamin D + Vitamin E)
  • Geri Tabs (Calcium (Calcium Phosphate (Dibasic)) + Copper Sulfate + Dl-Methionine + Ethinyl Estradiol + Folic Acid + Iodine + Iron Peptonized + Magnesium Oxide + Manganese Sulfate + Methyltestosterone + Nicotinamide + Phosphorus (Calcium Phosphate (Dibasic)) + Pyridoxine Hydrochloride + Thiamine Hydrochloride + Thyroid + Vitamin a + Vitamin B12 + Vitamin B2 + Vitamin D + Vitamin E)
  • Lo-Femenal 21 Tablets (Ethinyl Estradiol + Norgestrel)
  • Loestrin 1.5/30 21day Pak (Ethinyl Estradiol + Norethindrone Acetate)
  • Loestrin 1.5/30 28day Pack (Ethinyl Estradiol + Norethindrone Acetate)
  • Marvelon 21 Tab (Desogestrel + Ethinyl Estradiol)
  • Marvelon 28 Tab (Desogestrel + Ethinyl Estradiol)
  • Min-Ovral 21 (Ethinyl Estradiol + Levonorgestrel)
  • Min-Ovral 21 Tab (Ethinyl Estradiol + Levonorgestrel)
  • Min-Ovral 28 (Ethinyl Estradiol + Levonorgestrel)
  • Min-Ovral 28 Tab (Ethinyl Estradiol + Levonorgestrel)
  • Minestrin 1/20 21 (Ethinyl Estradiol + Norethindrone Acetate)
  • Minestrin 1/20 28 (Ethinyl Estradiol + Norethindrone Acetate)
  • Neo Mens Tab (Ethinyl Estradiol + Ethisterone)
  • Nuvaring (Ethinyl Estradiol + Etonogestrel)
  • Ortho Tablets (0.5/35, 1/35, 10/11, 7/7/7) (Ethinyl Estradiol + Norethindrone)
  • Ortho-Cept Tablets (Desogestrel + Ethinyl Estradiol)
  • Ovral 21 Tab (Ethinyl Estradiol + Norgestrel (Norgestrel))
  • Ovral 21 Tablets (Ethinyl Estradiol + Norgestrel (Norgestrel))
  • Ovral 28 Tablets (Ethinyl Estradiol + Norgestrel (Norgestrel))
  • Ovral 28tab (Ethinyl Estradiol + Norgestrel)
  • Preven Tablets (Ethinyl Estradiol + Levonorgestrel)
  • Select 1/35 (Ethinyl Estradiol + Norethindrone)
  • Synphasic 21 Tablets (Ethinyl Estradiol + Norethindrone)
  • Synphasic 28 Tablets (Ethinyl Estradiol + Norethindrone)
  • Synphasic-28 Tablets (Ethinyl Estradiol + Norethindrone)
  • Tri-Cyclen Lo (Ethinyl Estradiol + Norgestimate)
  • Tri-Cyclen Tablets - 21-Day (Ethinyl Estradiol + Norgestimate)
  • Tri-Cyclen Tablets - 28-Day (Ethinyl Estradiol + Norgestimate)
  • Triphasil 21 (Ethinyl Estradiol + Levonorgestrel)
  • Triphasil 21 Tab (Ethinyl Estradiol + Levonorgestrel)
  • Triphasil 28 (Ethinyl Estradiol + Levonorgestrel)
  • Triphasil 28 Tab (Ethinyl Estradiol + Levonorgestrel)
  • Triquilar 21 Tab (Ethinyl Estradiol + Levonorgestrel)
  • Triquilar 28 Tab (Ethinyl Estradiol + Levonorgestrel)
  • Yasmin 21 (Drospirenone + Ethinyl Estradiol)
  • Yasmin 28 (Drospirenone + Ethinyl Estradiol)
Categories
  • Estrogens
CAS number 57-63-6
Weight Average: 296.4034
Monoisotopic: 296.177630012
Chemical Formula C20H24O2
InChI Key InChIKey=BFPYWIDHMRZLRN-SLHNCBLASA-N
InChI
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
Plain Text
IUPAC Name
(1S,10R,11S,14R,15S)-14-ethynyl-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-triene-5,14-diol
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(O)C=C3
Plain Text
Mass Spec show (9.4 KB)
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Hydroxy Compounds
  • Naphthalenes
  • Alkynes
  • Phenols and Derivatives
  • Benzene and Derivatives
  • Alcohols and Polyols
  • Phenanthrenes
  • Aromatic compounds
  • Cyclohexenes and Derivatives
  • Phenyl Esters
Pharmacology
Indication For treatment of moderate to severe vasomotor symptoms associated with the menopause, female hypogonadism, prostatic carcinoma-palliative therapy of advanced disease, breast cancer, as an oral contraceptive, and as emergency contraceptive.
Pharmacodynamics Ethinyl estradiol is a synthetic derivative of the natural estrogen estradiol. It is one of two estrogens currently used in oral contraceptive pills. The other, mestranol, is converted to ethinyl estradiol before it is biologically active. Ethinyl estradiol and norethindrone are used together as an oral contraceptive agent.
Mechanism of action Estrogens diffuse into their target cells and interact with a protein receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase 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. This cascade is initiated by initially binding to the estrogen receptors. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).
Absorption Rapid and complete absorption follows oral intake of ethinyl estradiol (bioavailability 43%).
Volume of distribution Not Available
Protein binding 97%
Metabolism

Hepatic. Quantitatively, the major metabolic pathway for ethinyl estradiol, both in rats and in humans, is aromatic hydroxylation, as it is for the natural estrogens.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A4 2-hydroxyethinylestradiol 2-hydroxylation 2.5 0.91
Route of elimination Not Available
Half life 36 +/- 13 hours
Clearance Not Available
Toxicity Oral, mouse LD50: 1737 mg/kg. 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
  • Schering corp sub schering plough corp
  • Pharmacia and upjohn co
  • Organon usa inc
Packagers
Dosage forms
Form Route Strength
Cream Intravaginal
Insert, extended release Transdermal
Tablet Oral
Prices
Unit description Cost Unit
Ethinyl estradiol powder 140.0 USD g
Ortho-Cyclen (28) 28 0.25-35 mg-mcg tablet Disp Pack 38.99 USD disp
Ortho tri-cyclen lo tablet 2.68 USD tablet
Ortho-cyclen 28 tablet 1.13 USD tablet
Patents Not Available
Properties
State solid
Melting point 183 oC
Experimental Properties
Property Value Source
water solubility 11.3 mg/L PhysProp
logP 4.3 PhysProp
logS -4.3 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 6.77e-03 g/l ALOGPS
logP 3.63 ALOGPS
logP 3.81 ChemAxon Molconvert
logS -4.64 ALOGPS
pKa 17.59 ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 40.46 ChemAxon Molconvert
rotatable bond count 0 ChemAxon Molconvert
refractivity 87.37 ChemAxon Molconvert
polarizability 34.51 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00554 Link_out
KEGG Compound C07534 Link_out
PubChem Compound 5991 Link_out
PubChem Substance 46508618 Link_out
ChemSpider 5770 Link_out
ChEBI 4903 Link_out
ChEMBL 4903 Link_out
Therapeutic Targets Database DAP001018 Link_out
PharmGKB PA449527 Link_out
Drug Product Database 28231 Link_out
RxList http://www.rxlist.com/cgi/generic/estinyl.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Ethinylestradiol Link_out
ATC Codes
  • G03CA01
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (73.9 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. 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. Pubmed
  2. Garcia-Segura LM, Sanz A, Mendez P: Cross-talk between IGF-I and estradiol in the brain: focus on neuroprotection. Neuroendocrinology. 2006;84(4):275-9. Epub 2006 Nov 23. Pubmed
  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. Pubmed
  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 human epidermal growth factor receptor 2/phosphatidylinositol 3-kinase/Akt1 pathway. Endocrinology. 2007 Mar;148(3):1171-80. Epub 2006 Nov 30. Pubmed
  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. Pubmed
  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. Pubmed
  7. Bennink HJ: Reprint of Are all estrogens the same? Maturitas. 2008 Sep-Oct;61(1-2):195-201. Pubmed
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Orphan nuclear receptor PXR

Pharmacological action: unknown
Actions: agonist

Orphan receptor; its natural ligand is probably pregnane. Binds to a response element in the CYP3A4 and ABCB1/MDR1 genes promoter. Activates its expression in response to a wide variety of endobiotics and xenobiotics

Organism class: human
UniProt ID: O75469 Link_out
Gene: NR1I2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

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. 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. Pubmed

2. 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. 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. Pubmed
Transporters

1. Bile salt export pump

Actions: inhibitor, inducer

Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes

UniProt ID: O95342 Link_out
Gene: ABCB11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed

2. Sodium/bile acid cotransporter

Actions: inducer

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

UniProt ID: Q14973 Link_out
Gene: SLC10A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed

3. Canalicular multispecific organic anion transporter 1

Actions: inducer

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed

4. 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. 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. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 07, 2011 17:19

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.