Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C20H26O2 |
Molecular Weight | 298.4192 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 5 / 5 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]3([H])C4=C(CC[C@@]23[H])CC(=O)CC4
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
Molecular Formula | C20H26O2 |
Molecular Weight | 298.4192 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 5 / 5 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/12475720Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12475720
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12475720
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
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL208 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12475720 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Preventing | ENOVID Approved UseCombination 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 Date1961 |
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Primary | ENOVID Approved UseMenstrual disorder Launch Date1961 |
T1/2
Value | Dose | Co-administered | Analyte | Population |
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76 min |
single, intravenous |
NORETHYNODREL plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5% |
NORETHYNODREL plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: MALE food status: UNKNOWN |
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5% |
NORETHYNODREL plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse 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
AE | Significance | Dose | Population |
---|---|---|---|
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 |
PubMed
Title | Date | PubMed |
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Cardiovascular birth defects and antenatal exposure to female sex hormones. | 1977 Jan 13 |
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Induction of estrogen receptor-alpha and -beta activities by synthetic progestins. | 2000 Apr |
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Method for non-invasively recording electrocardiograms in conscious mice. | 2001 |
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[Effect of tibolone on vascular markers of human female coronary arteries - comparison with estradiol/norethisterone]. | 2001 Nov |
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Women's trials: the approval of the first oral contraceptive pill in the United States and Great Britain. | 2002 Apr |
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Hormonal content and potency of oral contraceptives and breast cancer risk among young women. | 2003 Jan 13 |
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Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor. | 2003 Oct |
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Behaviour of endocrine disrupting chemicals during the treatment of municipal sewage sludge. | 2004 |
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[Correlative changes of histomorphometry and biomechanical property of lumbar vertebrae body in ovariectomized rats]. | 2004 Apr |
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Suitability of N,O-bis(trimethylsilyl)trifluoroacetamide and N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide as derivatization reagents for the determination of the estrogens estrone and 17alpha-ethinylestradiol by gas chromatography-mass spectrometry. | 2004 Feb 13 |
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The involvement of CYP3A4 and CYP2C9 in the metabolism of 17 alpha-ethinylestradiol. | 2004 Nov |
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Removal of estrogenic activity and formation of oxidation products during ozonation of 17alpha-ethinylestradiol. | 2004 Oct 1 |
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Prenatal exposure of Long-Evans rats to 17alpha-ethinylestradiol modifies neither latent inhibition nor prepulse inhibition of the startle reflex but elicits minor deficits in exploratory behavior. | 2004 Sep 17 |
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Developmental effects of prenatal exposure to bisphenol a on the uterus of rat offspring. | 2004 Sep-Oct |
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Bioaccumulation of 14C-17alpha-ethinylestradiol by the aquatic oligochaete Lumbriculus variegatus in spiked artificial sediment. | 2005 Apr |
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Stereoselectivity in metabolic 3-reduction of tibolone in healthy Chinese female volunteers. | 2005 Dec |
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Relationship between ethinylestradiol-mediated changes in endocrine function and reproductive impairment in Japanese medaka (Oryzias latipes). | 2005 Feb |
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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 |
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Determination of endocrine disruptors in environmental waters using poly(acrylamide-vinylpyridine) monolithic capillary for in-tube solid-phase microextraction coupled to high-performance liquid chromatography with fluorescence detection. | 2005 Jul |
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Evaluation of genotoxic potential of norethynodrel in human lymphocytes in vitro. | 2005 Jun |
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The estrogenic activity of synthetic progestins used in oral contraceptives enhances fatty acid synthase-dependent breast cancer cell proliferation and survival. | 2005 Jun |
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Differential effects of estrogens and progestins on the anticoagulant tissue factor pathway inhibitor in the rat. | 2005 Mar |
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Effect of calcium channel modulators on temperature regulation in ovariectomized rats. | 2005 Mar |
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Potentiation of the vitellogenic response to 17alpha-ethinylestradiol by cortisol in the fathead minnow Pimephales promelas. | 2005 May |
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An environmentally relevant concentration of estrogen induces arrest of male gonad development in zebrafish, Danio rerio. | 2005 May |
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Long-term 17alpha-ethinyl estradiol treatment decreases cyclin E and cdk2 expression, reduces cdk2 kinase activity and inhibits S phase entry in regenerating rat liver. | 2005 Sep |
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Chemical birth of the pill. 1992. | 2006 Jan |
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Prediction of estrogen receptor agonists and characterization of associated molecular descriptors by statistical learning methods. | 2006 Nov |
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Beneficial effect of tibolone on mood, cognition, well-being, and sexuality in menopausal women. | 2006 Sep |
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A sesquineolignan with a spirodienone structure from Pinus sylvestris L. | 2007 |
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Can 19-nortestosterone derivatives be aromatized in the liver of adult humans? Are there clinical implications? | 2007 Aug |
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Benefits and risks of hormonal contraception for women. | 2007 Aug 10 |
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Postmenopausal tibolone therapy: biologic principles and applied clinical practice. | 2007 Jan 3 |
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Evaluation of extended and continuous use oral contraceptives. | 2008 Oct |
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Suppression of the inflammatory response in experimental arthritis is mediated via estrogen receptor alpha but not estrogen receptor beta. | 2010 |
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Optimization and prevalidation of the in vitro AR CALUX method to test androgenic and antiandrogenic activity of compounds. | 2010 Aug |
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Optimization and prevalidation of the in vitro ERalpha CALUX method to test estrogenic and antiestrogenic activity of compounds. | 2010 Aug |
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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 |
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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 |
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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 |
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Assessment of a recombinant androgen receptor binding assay: initial steps towards validation. | 2010 Aug |
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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 |
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New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an evolutionary step in birth control. | 2010 Aug 9 |
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Clinically relevant progestins regulate neurogenic and neuroprotective responses in vitro and in vivo. | 2010 Dec |
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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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12475720
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.
Substance Class |
Chemical
Created
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Record UNII |
88181ACA0M
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Record Status |
Validated (UNII)
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WHO-VATC |
QG03FA09
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G03FA09
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NCI_THESAURUS |
C776
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m8057
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SUB14666MIG
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Norethynodrel
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
Metabolite to parent drug ratio in non-uraemic human plasma.
Norethynodrel is metabolized in man to the antifertility agent norethisterone(norethindrone).
METABOLITE TO PARENT DRUG RATIO
PLASMA; URINE
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METABOLITE TOXIC -> PARENT |
The metabolite was implicated in production of delayed coma after methsuximide overdose in man.
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METABOLITE TOXIC -> PARENT |
The metabolite produced ataxia in man.
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METABOLITE -> PARENT |
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Related Record | Type | Details | ||
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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Related Record | Type | Details | ||
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ACTIVE MOIETY |