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.

Structure
Thumb
Synonyms
Not Available
External IDs
33355
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
NeconMestranol (0.05 mg/1) + Norethisterone (1 mg/1)KitActavis Pharma Company1967-11-172019-02-28Us
NorinylMestranol (0.05 mg/1) + Norethisterone (1 mg/1)KitActavis Pharma Company1967-11-17Not applicableUs
Norinyl 1/50 -(21-day Regimen)Mestranol (.05 mg) + Norethisterone (1 mg)TabletOralPfizer1996-11-042006-08-02Canada
Norinyl 1/50 -(28-day Regimen)Mestranol (0.05 mg) + Norethisterone (1 mg)TabletOralPfizer1998-05-202006-08-02Canada
Norinyl 1/50 21 TabMestranol (.05 mg) + Norethisterone (1 mg)TabletOralSyntex Inc.1965-12-311996-09-30Canada
Norinyl 1/50 28 TabMestranol (.05 mg) + Norethisterone (1 mg)TabletOralSyntex Inc.1965-12-311996-09-30Canada
Ortho-novumMestranol + NorethisteroneKitOrtho-McNeil Pharmaceutical, Inc.2006-10-202006-10-20Us
Ortho-novum 1/50 Tablets (21 Day)Mestranol (.05 mg) + Norethisterone (1 mg)TabletOralJanssen Pharmaceuticals1966-12-312004-10-12Canada
Ortho-novum 1/50 Tablets (28 Day)Mestranol (.05 mg) + Norethisterone (1 mg)TabletOralJanssen Pharmaceuticals1975-12-312001-06-18Canada
Categories
UNII
B2V233XGE7
CAS number
72-33-3
Weight
Average: 310.4299
Monoisotopic: 310.193280076
Chemical Formula
C21H26O2
InChI Key
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
IUPAC Name
(1S,10R,11S,14R,15S)-14-ethynyl-5-methoxy-15-methyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]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

Pharmacology

Indication

Mestranol was used as one of the first oral contraceptives.

Associated Conditions
Associated Therapies
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).

TargetActionsOrganism
AEstrogen receptor alpha
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinMestranol may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinMestranol may decrease the anticoagulant activities of (S)-Warfarin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Mestranol.
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Mestranol.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Mestranol.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Mestranol.
6-Deoxyerythronolide BThe metabolism of Mestranol can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Mestranol.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Mestranol.
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Mestranol.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015446
KEGG Drug
D00575
KEGG Compound
C07618
PubChem Compound
6291
PubChem Substance
46507679
ChemSpider
6054
ChEBI
6784
ChEMBL
CHEMBL1201151
Therapeutic Targets Database
DAP001014
PharmGKB
PA450388
Wikipedia
Mestranol

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of Ethinyl Estradiol and Norethindrone / Pharmacokinetics of Isavuconazole1
Not AvailableWithdrawnTreatmentIVF Poor Responders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Kit
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)150.5 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.00377 mg/mLALOGPS
logP3.89ALOGPS
logP4.04ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)17.59ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.46 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity91.86 m3·mol-1ChemAxon
Polarizability36.7 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9929
Blood Brain Barrier+0.9465
Caco-2 permeable+0.8463
P-glycoprotein substrateSubstrate0.656
P-glycoprotein inhibitor INon-inhibitor0.6099
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8148
CYP450 2C9 substrateNon-substrate0.7521
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7656
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9334
CYP450 2C19 inhibitorInhibitor0.7721
CYP450 3A4 inhibitorInhibitor0.5232
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7758
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8714
BiodegradationNot ready biodegradable0.9829
Rat acute toxicity1.5234 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8958
hERG inhibition (predictor II)Inhibitor0.5679
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (9.65 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-01t9-1972000000-5e394201ba0e38e5391f
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as estrane steroids. These are steroids with a structure based on the estrane skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Estrane steroids
Direct Parent
Estrane steroids
Alternative Parents
17-hydroxysteroids / Phenanthrenes and derivatives / Tetralins / Anisoles / Alkyl aryl ethers / Ynones / Tertiary alcohols / Cyclic alcohols and derivatives / Acetylides / Hydrocarbon derivatives
Substituents
Estrane-skeleton / Hydroxysteroid / 17-hydroxysteroid / Phenanthrene / Tetralin / Anisole / Alkyl aryl ether / Ynone / Benzenoid / Tertiary alcohol
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
terminal acetylenic compound, aromatic ether, 17beta-hydroxy steroid (CHEBI:6784)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
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 tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. 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. doi: 10.1186/ar3032. Epub 2010 May 24. [PubMed:20497523]
  2. 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 Aug;8(8):1838-46. doi: 10.1111/j.1538-7836.2010.03930.x. Epub 2010 May 27. [PubMed:20524981]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase 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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. 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:19515014]
  2. 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:9089421]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase 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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. PDR [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase 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 un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Gavhane YN, Yadav AV: Loss of orally administered drugs in GI tract. Saudi Pharm J. 2012 Oct;20(4):331-44. doi: 10.1016/j.jsps.2012.03.005. Epub 2012 Apr 20. [PubMed:23960808]

Drug created on July 06, 2007 13:51 / Updated on November 02, 2018 05:00