Details of the Drug

General Information of Drug (ID: DMG3F94)

Drug Name
Mestranol
Synonyms
Devocin; Menophase; Mestranolo; Mestranolum; Norquen; Ovastol; Component of Norinyl; Component of Norquen; Component of Ovulen; Ethynylestradiol methyl ether; Mestranol [Steroidal oestrogens]; Mestranolo [DCIT]; EE3ME; Ethinyl Estradiol 3 Methyl Ether; SC 4725; Component of Ortho-Novum; Delta-MVE; EE(sub3)ME; EthinylEstradiol 3-Methyl Ether; Ethinylestradiol 3-methyl ether; Ethinyloestradiol 3-methyl ether; Ethynylestradiol 3-methyl ether; Ethynyloestradiol 3-methyl ether; Inostral (steroid); Mestranolum [INN-Latin]; Mestranol (JP15/USP/INN); Mestranol [USAN:INN:BAN:JAN]; Alpha.-19-Norpregna-1,3,5(10)-trien-20-yn-17-ol, 3-meth; (17beta)-17-ethynyl-3-(methyloxy)estra-1,3,5(10)-trien-17-ol; 17-Ethynyl-3-methoxy-1,3,5(10)-oestratien-17-beta-ol; 17-Ethynyl-3-methoxyestra-1,3,5(10)-trien-17-ol; 17-Ethynylestradiol 3-methyl ether; 17-Ethynyloestradiol 3-methyl ether; 17-alpha-Ethinyl estradiol 3-methyl ether; 17-alpha-Ethinyl oestradiol 3-methyl ether; 17-alpha-Ethynyl-3-methoxy-1,3,5(10)-estratrien-17-beta-ol; 17-alpha-Ethynyloestradiol methyl ether; 17-ethynyl-3-methoxyestra-1(10),2,4-trien-17beta-ol; 17-ethynyl-3-methoxyoestra-1(10),2,4-trien-17beta-ol; 17alpha-Ethinyl estradiol 3-methyl ether; 17alpha-Ethinyl oestradiol 3-methyl ether; 17alpha-Ethinylestradiol 3-methyl ether; 17alpha-Ethynylestradiol 3-methyl ether; 17alpha-Ethynylestradiol methyl ether; 17alpha-Ethynyloestradiol 3-methyl ether; 17beta-Estradiol, 17-ethynyl-, 3-(methyl ether); 3-Methoxy-17-alpha-19-norpregna-1,3,5(10)-trien-20-yn-17-ol; 3-Methoxy-17-alpha-ethinylestradiol; 3-Methoxy-17-alpha-ethinyloestradiol; 3-Methoxy-17-alpha-ethynyl-1,3,5(10)-estratrien-17-beta-ol; 3-Methoxy-17-alpha-ethynyl-1,3,5(10)-oestratrien-17-beta-ol; 3-Methoxy-17-alpha-ethynylestradiol; 3-Methoxy-17-alpha-ethynyloestradiol; 3-Methoxy-17-ethynyloestradiol-17-beta; 3-Methoxy-17alpha-ethinylestradiol; 3-Methoxy-17alpha-ethinyloestradiol; 3-Methoxy-17alpha-ethynyl-1,3,5(10)-estratrien-17beta-ol; 3-Methoxy-17alpha-ethynyl-1,3,5(10)-oestratrien-17beta-ol; 3-Methoxy-17alpha-ethynylestradiol; 3-Methoxy-17alpha-ethynyloestradiol; 3-Methoxy-19-nor-17-alpha-pregna-1,3,5(10)-trien-20-yn-17-ol; 3-Methoxy-19-nor-17alpha-pregna-1,3,5(10)-trien-20-yn-17-ol; 3-Methoxy-19-norpregna-1,3,5(10)-trien-20-yn-17beta-ol; 3-Methoxyethynylestradiol; 3-Methoxyethynyloestradiol; 3-Methylethynylestradiol; 3-Methylethynyloestradiol; 3-O-Methylethynylestradiol
Indication
Disease Entry ICD 11 Status REF
Contraception QA21 Approved [1], [2]
Therapeutic Class
Estrogens
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 310.4
Topological Polar Surface Area (xlogp) 4
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 2
Chemical Identifiers
Formula
C21H26O2
IUPAC Name
(8R,9S,13S,14S,17R)-17-ethynyl-3-methoxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-ol
Canonical SMILES
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=C3C=CC(=C4)OC
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
InChIKey
IMSSROKUHAOUJS-MJCUULBUSA-N
Cross-matching ID
PubChem CID
6291
ChEBI ID
CHEBI:6784
CAS Number
72-33-3
DrugBank ID
DB01357
TTD ID
D0J1ML
INTEDE ID
DR1034

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Estrogen receptor (ESR) TTZAYWL ESR1_HUMAN Agonist [3]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [4]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [5]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Contraception
ICD Disease Classification QA21
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 9.78E-01 -3.38E-03 -5.71E-02
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 9.09E-01 -9.26E-02 -3.68E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 9.85E-01 2.24E-02 7.33E-02
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Mestranol (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Sarecycline DMLZNIQ Moderate Decreased absorption of Mestranol due to formation of complexes caused by Sarecycline . Acne vulgaris [ED80] [38]
Emapalumab DMZG5WL Moderate Altered metabolism of Mestranol due to Emapalumab alters the formation of CYP450 enzymes. Adaptive immunity immunodeficiency [4A01] [39]
Siltuximab DMGEATB Moderate Altered metabolism of Mestranol due to Siltuximab alters the formation of CYP450 enzymes. Anemia [3A00-3A9Z] [39]
ABT-492 DMJFD2I Moderate Decreased absorption of Mestranol due to formation of complexes caused by ABT-492. Bacterial infection [1A00-1C4Z] [38]
Omadacycline DMR2J95 Moderate Decreased absorption of Mestranol due to formation of complexes caused by Omadacycline. Bacterial infection [1A00-1C4Z] [38]
Alpelisib DMEXMYK Moderate Increased metabolism of Mestranol caused by Alpelisib mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [40]
Linaclotide DM4EGV0 Moderate Altered absorption of Mestranol caused by Linaclotide. Irritable bowel syndrome [DD91] [41]
R0-93877 DMM4U9G Moderate Altered absorption of Mestranol caused by R0-93877. Irritable bowel syndrome [DD91] [42]
Exjade DMHPRWG Moderate Increased metabolism of Mestranol caused by Exjade mediated induction of CYP450 enzyme. Mineral absorption/transport disorder [5C64] [43]
Carfilzomib DM48K0X Major Additive thrombogenic effects by the combination of Mestranol and Carfilzomib. Multiple myeloma [2A83] [44]
Romidepsin DMT5GNL Moderate Antagonize the effect of Mestranol when combined with Romidepsin. Mycosis fungoides [2B01] [40]
Ustekinumab DMHTYK3 Moderate Altered metabolism of Mestranol due to Ustekinumab alters the formation of CYP450 enzymes. Psoriasis [EA90] [39]
Tocilizumab DM7J6OR Moderate Altered metabolism of Mestranol due to Tocilizumab alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [39]
Rilonacept DMGLUQS Moderate Altered metabolism of Mestranol due to Rilonacept alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [39]
Sarilumab DMOGNXY Moderate Altered metabolism of Mestranol due to Sarilumab alters the formation of CYP450 enzymes. Rheumatoid arthritis [FA20] [39]
⏷ Show the Full List of 15 DDI Information of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7087).
2 FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 010976.
3 Short-term effects of environmentally relevant concentrations of EDC mixtures on Mytilus galloprovincialis digestive gland. Aquat Toxicol. 2008 May 30;87(4):272-9.
4 Prescribrt's digital referenve - Ethinyl estradiol/norethindrone; mestranol/norethindrone - Drug Summary
5 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.
6 Loss of orally administered drugs in GI tract. Saudi Pharm J. 2012 Oct;20(4):331-44.
7 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
8 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
9 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
10 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
11 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
12 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
13 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
14 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
15 Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
16 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
17 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
18 Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
19 Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
20 Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
21 PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
22 Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
23 Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
24 Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
25 Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
26 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
27 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
28 New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
29 A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
30 A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
31 Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause. Recent Pat Cardiovasc Drug Discov. 2008 Nov;3(3):165-86.
32 Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
33 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
34 17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
35 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 620).
36 Clinical pipeline report, company report or official report of Shionogi (2011).
37 Effect of selective estrogen receptor modulators on cell proliferation and estrogen receptor activities in normal human prostate stromal and epithe... Prostate Cancer Prostatic Dis. 2009;12(4):375-81.
38 Friedman CI, Huneke AL, Kim MH, Powell J "The effect of ampicillin on oral contraceptive effectiveness." Obstet Gynecol 55 (1980): 33-7. [PMID: 7188714]
39 Product Information. Cosentyx (secukinumab). Novartis Pharmaceuticals, East Hanover, NJ.
40 Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32. [PMID: 9562227]
41 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
42 Cerner Multum, Inc. "Australian Product Information.".
43 Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
44 Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception.".