DrugBank: Mestranol (DB01357)

targets (1) enzymes (1)

Identification

Name

Mestranol

Accession Number

DB01357

Type

small molecule

Groups

approved

Description

The 3-methyl ether of ethinyl estradiol. It must be demethylated to be biologically active. It is used as the estrogen component of many combination ORAL contraceptives. [PubChem]

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Brand names

Not Available

Brand name mixtures

Not Available

Categories

Estrogens

CAS number

72-33-3

Weight

Average: 310.4299
Monoisotopic: 310.193280076

Chemical Formula

C₂₁H₂₆O₂

InChI Key

InChIKey=IMSSROKUHAOUJS-MJCUULBUSA-N

InChI

InChI=1S/C21H26O2/c1-4-21(22)12-10-19-18-7-5-14-13-15(23-3)6-8-16(14)17(18)9-11-20(19,21)2/h1,6,8,13,17-19,22H,5,7,9-12H2,2-3H3/t17-,18-,19+,20+,21+/m1/s1

Plain Text

IUPAC Name

(1S,10R,11S,14R,15S)-14-ethynyl-5-methoxy-15-methyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-2(7),3,5-trien-14-ol

SMILES

[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(OC)C=C3

Plain Text

Mass Spec

show (9.6 KB)

Taxonomy

Kingdom

Organic

Classes

Steroids and Steroid Derivatives

Substructures

Steroids and Steroid Derivatives
Hydroxy Compounds
Naphthalenes
Alkynes
Phenols and Derivatives
Ethers
Benzene and Derivatives
Alcohols and Polyols
Phenanthrenes
Aromatic compounds
Anisoles
Cyclohexenes and Derivatives
Phenyl Esters

Pharmacology

Indication

Mestranol was used as one of the first oral contraceptives.

Pharmacodynamics

Not Available

Mechanism of action

Mestranol is the 3-methyl ether of ethinylestradiol. Ethinylestradiol, is a synthetic derivative of estradiol. Ethinylestradiol is orally bio-active and the estrogen used in almost all modern formulations of combined oral contraceptive pills. It binds to (and activates) the estrogen receptor. Mestranol is a biologically inactive prodrug of ethinylestradiol to which it is demethylated in the liver with a conversion efficiency of 70%. 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. 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

Enzyme	Metabolite	Reaction	K_m	V_max
Cytochrome P450 2C9	17-alpha-ethinyl estradiol	Demethylation

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Not Available

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

solid

Melting point

150.5 oC

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
water solubility	3.77e-03 g/l	ALOGPS
logP	3.89	ALOGPS
logP	3.96	ChemAxon Molconvert
logS	-4.92	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	2	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	29.46	ChemAxon Molconvert
rotatable bond count	1	ChemAxon Molconvert
refractivity	91.86	ChemAxon Molconvert
polarizability	36.71	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D00575
KEGG Compound	C07618
PubChem Compound	6291
PubChem Substance	46507679
ChemSpider	6054
ChEBI	6784
ChEMBL	6784
Therapeutic Targets Database	DAP001014
PharmGKB	PA450388
Drug Product Database	0
Wikipedia	http://en.wikipedia.org/wiki/Mestranol

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

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 Gene: ESR1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Dulos J, Vijn P, van Doorn C, Hofstra CL, Veening-Griffioen D, de Graaf J, Dijcks FA, Boots AM: Suppression of the inflammatory response in experimental arthritis is mediated via estrogen receptor alpha but not estrogen receptor beta. Arthritis Res Ther. 2010;12(3):R101. Epub 2010 May 24. Pubmed Cleuren AC, van der Linden IK, de Visser YP, Wagenaar GT, Reitsma PH, van Vlijmen BJ: 17alpha-Ethinylestradiol rapidly alters transcript levels of murine coagulation genes via estrogen receptor alpha. J Thromb Haemost. 2010 May 27. Pubmed Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

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:

Dulos J, Vijn P, van Doorn C, Hofstra CL, Veening-Griffioen D, de Graaf J, Dijcks FA, Boots AM: Suppression of the inflammatory response in experimental arthritis is mediated via estrogen receptor alpha but not estrogen receptor beta. Arthritis Res Ther. 2010;12(3):R101. Epub 2010 May 24. Pubmed
Cleuren AC, van der Linden IK, de Visser YP, Wagenaar GT, Reitsma PH, van Vlijmen BJ: 17alpha-Ethinylestradiol rapidly alters transcript levels of murine coagulation genes via estrogen receptor alpha. J Thromb Haemost. 2010 May 27. Pubmed
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes
1. Cytochrome P450 2C9 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 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 Gene: CYP2C9 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed Schmider J, Greenblatt DJ, von Moltke LL, Karsov D, Vena R, Friedman HL, Shader RI: Biotransformation of mestranol to ethinyl estradiol in vitro: the role of cytochrome P-450 2C9 and metabolic inhibitors. J Clin Pharmacol. 1997 Mar;37(3):193-200. Pubmed

Enzymes

1. Cytochrome P450 2C9

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 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:

Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
Schmider J, Greenblatt DJ, von Moltke LL, Karsov D, Vena R, Friedman HL, Shader RI: Biotransformation of mestranol to ethinyl estradiol in vitro: the role of cytochrome P-450 2C9 and metabolic inhibitors. J Clin Pharmacol. 1997 Mar;37(3):193-200. Pubmed

Comments

Drug created on July 06, 2007 13:51 / Updated on June 13, 2011 17:43

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