MESTRANOL

US Previously Marketed

First approved in 1957

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H26O2
Molecular Weight	310.4299
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]3([H])C4=C(CC[C@@]23[H])C=C(OC)C=C4

InChI

InChIKey=IMSSROKUHAOUJS-MJCUULBUSA-N

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

HIDE SMILES / InChI

Molecular Formula	C21H26O2
Molecular Weight	310.4299
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.drugs.com/ppa/norethindrone-and-mestranol.html

Mestranol is a biologically inactive prodrug of estrogen agonist ethinylestradiol. Enovid, a combination of mestranol and noretynodrel, was first oral contraceptive approved by FDA in 1960.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor alpha 127 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/536998	Agonist 2678		15.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pregnancy 65 Sources: https://www.drugs.com/ppa/norethindrone-and-mestranol.html	Preventing		Approved 8429	ENOVID Approved Use Combination oral contraceptives inhibit ovulation via a negative feedback mechanism on the hypothalamus, which alters the normal pattern of gonadotropin secretion of a follicle-stimulating hormone (FSH) and luteinizing hormone by the anterior pituitary. The follicular phase FSH and midcycle surge of gonadotropins are inhibited. In addition, combination hormonal contraceptives produce alterations in the genital tract, including changes in the cervical mucus, rendering it unfavorable for sperm penetration even if ovulation occurs. Changes in the endometrium may also occur, producing an unfavorable environment for nidation. Combination hormonal contraceptive drugs may alter the tubal transport of the ova through the fallopian tubes. Progestational agents may also alter sperm fertility. Launch Date -2.78207988E11
Menstrual cycle disorder 5 Sources: http://www.fda.gov/AboutFDA/WhatWeDo/History/ProductRegulation/SelectionsFromFDLIUpdateSeriesonFDAHistory/ucm092009.htm	Primary		Approved 8429	ENOVID Approved Use Menstrual disorder

C_max

Value	Dose	Co-administered	Analyte	Population
175 pg/mL EXPERIMENT https://www.sciencedirect.com/science/article/abs/pii/000293789090550Q	50 μg single, oral dose: 50 μg route of administration: Oral experiment type: SINGLE co-administered:		ETHINYL ESTRADIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
963 pg × min/mL EXPERIMENT https://www.sciencedirect.com/science/article/abs/pii/000293789090550Q	50 μg single, oral dose: 50 μg route of administration: Oral experiment type: SINGLE co-administered:		ETHINYL ESTRADIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6 h EXPERIMENT https://www.sciencedirect.com/science/article/abs/pii/000293789090550Q	50 μg single, oral dose: 50 μg route of administration: Oral experiment type: SINGLE co-administered:		ETHINYL ESTRADIOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
80 ug 1 times / day multiple, oral Dose: 80 ug, 1 times / day Route: oral Route: multiple Dose: 80 ug, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4429085	healthy, 20-26 years Health Status: healthy Age Group: 20-26 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/4429085	Sources: https://pubmed.ncbi.nlm.nih.gov/4429085
50 ug single, intravenous Dose: 50 ug Route: intravenous Route: single Dose: 50 ug Sources: https://pubmed.ncbi.nlm.nih.gov/4853600	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/4853600	Sources: https://pubmed.ncbi.nlm.nih.gov/4853600

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1037

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9089421/;https://pubmed.ncbi.nlm.nih.gov/25924705/	yes		yes (pharmacogenomic study) Comment: majority of tested variants exhibited decreased clearance values compared to wild type, except for CYP2C940 and 36 Sources: https://pubmed.ncbi.nlm.nih.gov/9089421/;https://pubmed.ncbi.nlm.nih.gov/25924705/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6784	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6784
ChemicalBook	CB7426942	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7426942
MolPort	MolPort-002-507-152	https://www.molport.com/shop/molecule-link/MolPort-002-507-152
Selleck Chemicals	Mestranol	http://www.selleckchem.com/products/Mestranol.html
ZINC	ZINC000003815424	http://zinc15.docking.org/substances/ZINC000003815424
eMolecules	29536264	https://www.emolecules.com/cgi-bin/more?vid=29536264
eMolecules	511126	https://www.emolecules.com/cgi-bin/more?vid=511126

PubMed

Title	Date	PubMed
Depression and oral contraceptives.	1968 Aug 24	4174173
The contraceptive pill and major arterial emboli in a teen-aged girl.	1968 Oct 12	5700689
[Arterial hypertension during treatment with estro-progestative drugs].	1971 Sep-Oct	5153254
Mesenteric venous thrombosis in two women taking oral contraceptives.	1973 May	4121539
Letter: Oral contraceptives and malignant hepatoma.	1976 Feb 28	55736
Vascular complications of long-term oestrogen therapy.	1977	614942
Cardiovascular birth defects and antenatal exposure to female sex hormones.	1977 Jan 13	830309
Asymptomatic liver cell adenomas. Another case of resolution after discontinuation of oral contraceptive use.	1978 Apr 21	204807
Hormone replacement treatment and benign intracranial hypertension.	1982 Jun 5	6805652
Oral contraception and cerebral thrombosis in a Jamaican.	1983 Sep	6636726
Enhancement of hepatocarcinogenesis in female rats by ethinyl estradiol and mestranol but not estradiol.	1984 Sep	6744303
Xenobiotic interaction with and alteration of channel catfish estrogen receptor.	1997 Dec	9439733
A binary screening assay for pro-oestrogens in food: metabolic activation using hepatic microsomes and detection with oestrogen sensitive recombinant yeast cells.	2002 Dec	12623674
Differential expression of c-fos and c-myc protooncogenes by estrogens, xenobiotics and other growth-stimulatory agents in primary rat hepatocytes.	2003 Mar	12632255
Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds with both receptor types.	2004 Jul	15276617
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.	2006 Nov	16497524
Rat α-Fetoprotein binding affinities of a large set of structurally diverse chemicals elucidated the relationships between structures and binding affinities.	2012 Nov 19	23013281
Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein.	2015 Feb	25349334

Patents

Sample Use Guides

In Vivo Use Guide

Dose starts on first day of menstrual cycle taking 1 tablet daily.

Route of Administration: Oral

In Vitro Use Guide

In vitro estrogen receptor binding affinity was determined using uterine cytosol preparation. Reaction mixture contained 0.7 ug of protein from the receptor preparation and 16000 dpm of 17beta[3H]estradiol in 0.25 mL of 0.01 Tris-HCl buffer, pH 8.0, containing 0.001 M EDTA and 0.25 M sucrose. Compound was tested in a dose-response fashion using 8 concentration from 0.1 nM to 100 000 nM in duplicate. After incubation at 4°C for 16-18 h, the compounds bound to the receptor were separated from those free in solution using dextran-coated charcoal. The amount of radioactivity bound to the receptor was quantified in Aquasol using liquid scintillation spectrometer. Mestranol did not bound to estrogen receptor in concetrations up to 100 uM, but its metabolite displaced estradiol with IC50 of 15 nM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 14:58:16 UTC 2023` Edited by `admin` on `Fri Dec 15 14:58:16 UTC 2023`
Record UNII	B2V233XGE7
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MESTRANOL

Official Name

English

NSC-84032

Code

English

MESTRANOL [EP MONOGRAPH]

Common Name

English

EE3-ME

Code

English

MESTRANOL [HSDB]

Common Name

English

MESTRANOL [VANDF]

Common Name

English

OVULEN COMPONENT MESTRANOL

Common Name

English

MESTRANOL [JAN]

Common Name

English

MESTRANOL COMPONENT OF ENOVID

Common Name

English

MESTRANOL [ORANGE BOOK]

Common Name

English

EE-3ME

Code

English

EE3ME

Code

English

MESTRANOL [MI]

Common Name

English

33355

Code

English

MESTRANOL [USP-RS]

Common Name

English

MESTRANOL [USP MONOGRAPH]

Common Name

English

MESTRANOL [MART.]

Common Name

English

EEI3ME

Code

English

Mestranol [WHO-DD]

Common Name

English

mestranol [INN]

Common Name

English

3-METHOXY-19-NOR-17.ALPHA.-PREGNA-1,3,5(10)-TRIEN-20-YN-17-OL.

Common Name

English

19-NORPREGNA-1,3,5(10)-TRIEN-20-YN-17-OL, 3-METHOXY-, (17.ALPHA.)-

Common Name

English

MESTRANOL COMPONENT OF OVULEN

Common Name

English

ENOVID COMPONENT MESTRANOL

Common Name

English

MESTRANOL [USAN]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000000100