U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H26O2
Molecular Weight 298.42
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NORETHYNODREL

SMILES

C#C[C@@]1(CC[C@@]2([H])[C@]3([H])CCC4=C(CCC(=O)C4)[C@@]3([H])CC[C@@]21C)O

InChI

InChIKey=ICTXHFFSOAJUMG-SLHNCBLASA-N
InChI=1S/C20H26O2/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/h1,16-18,22H,4-12H2,2H3/t16-,17-,18+,19+,20+/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12475720

Norethynodrel is a steroidal progestin of the 19-nortestosterone group and an isomer of norethisterone. Norethynodrel is a progesteron agonist with very weak estrogenic activiry. Noretynodrel was introduced in 1957 in Enovid, a combination formulation of noretynodrel and mestranol, for the treatment of gynecological and menstrual disorders.A few years later, in May 1960, Enovid was also approved as the first oral contraceptive.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
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
Primary
ENOVID

Approved Use

Menstrual disorder

Launch Date

-2.78207988E11
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
76 min
single, intravenous
NORETHYNODREL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
NORETHYNODREL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: MALE
food status: UNKNOWN
5%
NORETHYNODREL plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.122
healthy, 25
n = 1
Health Status: healthy
Condition: Contraception
Age Group: 25
Sex: F
Population Size: 1
Sources: Page: p.122
Disc. AE: Thromboembolic event...
AEs leading to
discontinuation/dose reduction:
Thromboembolic event
Sources: Page: p.122
AEs

AEs

AESignificanceDosePopulation
Thromboembolic event Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.122
healthy, 25
n = 1
Health Status: healthy
Condition: Contraception
Age Group: 25
Sex: F
Population Size: 1
Sources: Page: p.122
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as victim
PubMed

PubMed

TitleDatePubMed
Cardiovascular birth defects and antenatal exposure to female sex hormones.
1977 Jan 13
Method for non-invasively recording electrocardiograms in conscious mice.
2001
Women's trials: the approval of the first oral contraceptive pill in the United States and Great Britain.
2002 Apr
Hormonal content and potency of oral contraceptives and breast cancer risk among young women.
2003 Jan 13
Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor.
2003 Oct
Behaviour of endocrine disrupting chemicals during the treatment of municipal sewage sludge.
2004
The involvement of CYP3A4 and CYP2C9 in the metabolism of 17 alpha-ethinylestradiol.
2004 Nov
Removal of estrogenic activity and formation of oxidation products during ozonation of 17alpha-ethinylestradiol.
2004 Oct 1
Developmental effects of prenatal exposure to bisphenol a on the uterus of rat offspring.
2004 Sep-Oct
p-Toluenesulfonyl isocyanate as a novel derivatization reagent to enhance the electrospray ionization and its application in the determination of two stereo isomers of 3-hydroxyl-7-methyl-norethynodrel in plasma.
2005 Jan 25
Evaluation of genotoxic potential of norethynodrel in human lymphocytes in vitro.
2005 Jun
The estrogenic activity of synthetic progestins used in oral contraceptives enhances fatty acid synthase-dependent breast cancer cell proliferation and survival.
2005 Jun
An environmentally relevant concentration of estrogen induces arrest of male gonad development in zebrafish, Danio rerio.
2005 May
Chemical birth of the pill. 1992.
2006 Jan
Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods.
2006 Nov
Beneficial effect of tibolone on mood, cognition, well-being, and sexuality in menopausal women.
2006 Sep
A sesquineolignan with a spirodienone structure from Pinus sylvestris L.
2007
Can 19-nortestosterone derivatives be aromatized in the liver of adult humans? Are there clinical implications?
2007 Aug
Benefits and risks of hormonal contraception for women.
2007 Aug 10
Postmenopausal tibolone therapy: biologic principles and applied clinical practice.
2007 Jan 3
Evaluation of extended and continuous use oral contraceptives.
2008 Oct
Suppression of the inflammatory response in experimental arthritis is mediated via estrogen receptor alpha but not estrogen receptor beta.
2010
Optimization and prevalidation of the in vitro AR CALUX method to test androgenic and antiandrogenic activity of compounds.
2010 Aug
Optimization and prevalidation of the in vitro ERalpha CALUX method to test estrogenic and antiestrogenic activity of compounds.
2010 Aug
The assessment of estrogenic or anti-estrogenic activity of chemicals by the human stably transfected estrogen sensitive MELN cell line: results of test performance and transferability.
2010 Aug
Assessment of a robust model protocol with accelerated throughput for a human recombinant full length estrogen receptor-alpha binding assay: protocol optimization and intralaboratory assay performance as initial steps towards validation.
2010 Aug
Screening for (anti)androgenic properties using a standard operation protocol based on the human stably transfected androgen sensitive PALM cell line. First steps towards validation.
2010 Aug
Assessment of a recombinant androgen receptor binding assay: initial steps towards validation.
2010 Aug
The lowest-dose, extended-cycle combined oral contraceptive pill with continuous ethinyl estradiol in the United States: a review of the literature on ethinyl estradiol 20 μg/levonorgestrel 100 μg + ethinyl estradiol 10 μg.
2010 Aug 10
New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an evolutionary step in birth control.
2010 Aug 9
Clinically relevant progestins regulate neurogenic and neuroprotective responses in vitro and in vivo.
2010 Dec
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
Patents

Sample Use Guides

Dose starts on first day of menstrual cycle taking 1 tablet daily.
Route of Administration: Oral
For transactivation studies CHO cells stably transfected with hER-RO-LUC, hER-RO-LUC, hAR-MMTVLUC, hPR-B-MMTV-LUC, hPR-A-MMTV-LUC or hGRMMTV-LUC were used. 5 × 104 cells/well were seeded into a 96-well plate and incubated with compounds (final ethanol content: 1% v/v) for 16 h in medium with 5% charcoal-treated supplemented defined bovine calf serum at 37°C in a humidified atmosphere of air supplemented with 5% CO2. Of the total 250uL incubation volume, 200 uLl was removed, and 50 uL LucLite was added for cell lysis and luciferase measurement. Luciferase activity was measured in a Topcount luminescence counter (Canberra Packard). Relative agonistic activity (RAA) studies were carried out with various concentrations of the standards (1:2:4 dilutions) and compounds of interest. The RAA was determined to Org 2058 (PRA and PRB). Full agonistic curves for PRA, PRB were also determined in the CHO cells described before. The concentrations of the compounds used were 10−5 to 10−12 mol/l with a dilution factor of 3.16. Norethynodrel displayed agonistic activity with respect to PRA with EC50 of 10 nM, and PRB with EC50 of below 1 nM.
Name Type Language
NORETHYNODREL
HSDB   MI   ORANGE BOOK   USAN   USP   VANDF  
USAN  
Official Name English
19-NORPREGN-5(10)-EN-20-YN-3-ONE, 17-HYDROXY-, (17.ALPHA.)-
Common Name English
SC-4642
Code English
NORETHYNODREL [USAN]
Common Name English
NORETHYNODREL [MI]
Common Name English
ENIDREL
Common Name English
NORETYNODREL
INN   MART.   WHO-DD  
INN  
Official Name English
NORETYNODREL [MART.]
Common Name English
ENOVID COMPONENT NORETHYNODREL
Common Name English
13-METHYL-17-ETHYNYL-17-HYDROXY-1,2,3,4,6,7,8,9,11,12,13,14,16,17-TETRADECAHYDRO-15H-CYCLOPENTA(A)PHENANTHREN-3-ONE
Systematic Name English
NSC-15432
Code English
NORETHYNODREL [VANDF]
Common Name English
NORETHYNODREL [USP]
Common Name English
NORETYNODREL [WHO-DD]
Common Name English
NORETYNODREL [INN]
Common Name English
NORETHYNODREL COMPONENT OF ENOVID
Common Name English
NORETHYNODREL [ORANGE BOOK]
Common Name English
17-HYDROXY-19-NOR-17.ALPHA.-PREGN-5(10)-EN-20-YN-3-ONE
Common Name English
NORETHYNODREL [HSDB]
Common Name English
Classification Tree Code System Code
WHO-VATC QG03FA09
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
WHO-ATC G03FA09
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
NCI_THESAURUS C776
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
Code System Code Type Description
FDA UNII
88181ACA0M
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
MERCK INDEX
M8057
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY Merck Index
EVMPD
SUB14666MIG
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
ALTERNATIVE
DRUG BANK
DB09371
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
DRUG CENTRAL
1965
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
MESH
D009641
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
WIKIPEDIA
NORETHYNODREL
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
EPA CompTox
68-23-5
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
PUBCHEM
6231
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-682-1
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
HSDB
2951
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
CAS
68-23-5
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
ChEMBL
CHEMBL1387
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
RXCUI
7515
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY RxNorm
EVMPD
SUB12439MIG
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
INN
1257
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
NCI_THESAURUS
C66244
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY
LACTMED
Norethynodrel
Created by admin on Sat Jun 26 11:19:49 UTC 2021 , Edited by admin on Sat Jun 26 11:19:49 UTC 2021
PRIMARY