General Information of Drug (ID: DR1034)
Drug Name
Mestranol
Synonyms
Menophase; Mestranolo [DCIT]; Mestranolum; Mestranolum [INN-Latin]; Norquen; Ovastol; Devocin; EE(sub3)ME; Ethinylestradiol 3-methyl ether; Ethynylestradiol 3-methyl ether; Ethynylestradiol methyl ether; Ethynyloestradiol 3-methyl ether; Inostral (steroid); SC 4725; delta-MVE; mestranol; 3-Methoxy-17alpha-ethynylestradiol; 3-Methoxyethynylestradiol; 3-Methoxyethynyloestradiol; 3-Methylethynylestradiol; Compound 33355; 3-Methylethynyloestradiol; 3-O-Methylethynylestradiol; 72-33-3; Caswell No. 547A; EE3ME
Indication Menorrhagia [ICD11: GA20] Phase 4 [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 310.4 Topological Polar Surface Area 29.5
Heavy Atom Count 23 Rotatable Bond Count 2
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 2
Cross-matching ID
PubChem CID
6291
PubChem SID
9820 ; 221722 ; 3139632 ; 7847641 ; 7979911 ; 8139980 ; 8153967 ; 10321875 ; 11466874 ; 11467994 ; 11486488 ; 12146110 ; 14870200 ; 24888219 ; 25621811 ; 29215140 ; 29225285 ; 46386940 ; 46507679 ; 47365356 ; 47662462 ; 47810914 ; 48035293 ; 48413978 ; 48416225 ; 48421896 ; 49698659 ; 49857464 ; 50124123 ; 53788967 ; 56313760 ; 56352889 ; 56422167 ; 78791185 ; 85787338 ; 92125797 ; 92308432 ; 92712421 ; 93165651 ; 103771134 ; 103914355 ; 104253458 ; 104311640 ; 121363468 ; 124659052 ; 124757588 ; 124799544 ; 124891600 ; 125164392 ; 126630112
ChEBI ID
ChEBI:6784
CAS Number
72-33-3
TTD Drug ID
D0J1ML
Formula
C21H26O2
Canonical SMILES
CC12CCC3C(C1CCC2(C#C)O)CCC4=C3C=CC(=C4)OC
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
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
17alpha-Ethinylestradiol DM002643
5991
Oxidation - O-Demethylation 1 [3] , [6]
17beta-Ethinylestradiol DM002647
145760
Oxidation - O-Demethylation 1 [3]
16alpha-hydroxyethinylestradiol DM000918
11723045
Oxidation - 16-Hydroxylation 2 [7] , [8]
2-hydroxyethinylestradiol DM000910
71777553
Oxidation - 2-Hydroxylation 2 [7] , [8]
4-hydroxyethinylestradiol DM000912
21114722
Oxidation - 4-Hydroxylation 2 [7] , [8]
6-hydroxyethinylestradiol DM000914
21121304
Oxidation - 6-Hydroxylation 2 [7] , [8]
7-hydroxyethinylestradiol DM000916 N. A. Oxidation - 7-Hydroxylation 2 [7] , [8]
Ethinylestradiol-3-sulfate DM000920
40561833
Conjugation - Sulfation 2 [5]
N-desmethylzopiclone metabolite DM002646
53785275
Conjugation - O-Glucuronidation 2 [7] , [9] , [10]
16alpha-methoxyethinylestradiol DM000919 N. A. Conjugation - O-Methylation 3 [7] , [8]
2-methoxyethinylestradiol DM000911
90470385
Conjugation - O-Methylation 3 [7] , [8]
4-methoxyethinylestradiol DM000913 N. A. Conjugation - O-Methylation 3 [7] , [8]
6-methoxyethinylestradiol DM000915 N. A. Conjugation - O-Methylation 3 [7] , [8]
7-methoxyethinylestradiol DM000917 N. A. Conjugation - O-Methylation 3 [7] , [8]
⏷ Show the Full List of 14  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001652 Mestranol 17alpha-Ethinylestradiol Oxidation - O-Demethylation CYP2C9 [3], [6]
MR001653 Mestranol 17beta-Ethinylestradiol Oxidation - O-Demethylation CYP2C9 [3]
MR001645 17alpha-Ethinylestradiol 2-hydroxyethinylestradiol Oxidation - 2-Hydroxylation CYP2C8 ... [7], [8]
MR001646 17alpha-Ethinylestradiol 4-hydroxyethinylestradiol Oxidation - 4-Hydroxylation CYP2C8 ... [7], [8]
MR001647 17alpha-Ethinylestradiol 6-hydroxyethinylestradiol Oxidation - 6-Hydroxylation CYP2C8 ... [7], [8]
MR001648 17alpha-Ethinylestradiol 7-hydroxyethinylestradiol Oxidation - 7-Hydroxylation CYP2C8 ... [7], [8]
MR001649 17alpha-Ethinylestradiol 16alpha-hydroxyethinylestradiol Oxidation - 16-Hydroxylation CYP2C8 ... [7], [8]
MR001650 17alpha-Ethinylestradiol Ethinylestradiol-3-sulfate Conjugation - Sulfation EST ... [5]
MR001651 17alpha-Ethinylestradiol N-desmethylzopiclone metabolite Conjugation - O-Glucuronidation UGT1A9 ... [7], [9], [10]
MR001644 16alpha-hydroxyethinylestradiol 16alpha-methoxyethinylestradiol Conjugation - O-Methylation COMT [7], [8]
MR001640 2-hydroxyethinylestradiol 2-methoxyethinylestradiol Conjugation - O-Methylation COMT [7], [8]
MR001641 4-hydroxyethinylestradiol 4-methoxyethinylestradiol Conjugation - O-Methylation COMT [7], [8]
MR001642 6-hydroxyethinylestradiol 6-methoxyethinylestradiol Conjugation - O-Methylation COMT [7], [8]
MR001643 7-hydroxyethinylestradiol 7-methoxyethinylestradiol Conjugation - O-Methylation COMT [7], [8]
⏷ Show the Full List of 14 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
Sulfotransferase 1A4 (SULT1A4) DMEN007 Homo sapiens
ST1A4_HUMAN
1.14.13.39
[5]
References
1 The Drugs.com International Drug Name Database: Mestranol
2 Loss of orally administered drugs in GI tract. Saudi Pharm J. 2012 Oct;20(4):331-44.
3 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.
4 Prescribrt's digital referenve - Ethinyl estradiol/norethindrone; mestranol/norethindrone - Drug Summary
5 Sulfotransferase 1E1 is a low km isoform mediating the 3-O-sulfation of ethinyl estradiol Drug Metab Dispos. 2004 Nov;32(11):1299-303. doi: 10.1124/dmd.32.11..
6 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.
7 Genetic variation in the first-pass metabolism of ethinylestradiol, sex hormone binding globulin levels and venous thrombosis risk Eur J Intern Med. 2017 Jul;42:54-60. doi: 10.1016/j.ejim.2017.05.019.
8 Metabolism of 17 alpha-ethinylestradiol by human liver microsomes in vitro: aromatic hydroxylation and irreversible protein binding of metabolites J Clin Endocrinol Metab. 1974 Dec;39(6):1072-80. doi: 10.1210/jcem-39-6-1072.
9 Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol Mol Pharmacol. 1993 Apr;43(4):649-54.
10 The potent inhibition of human cytosolic sulfotransferase 1A1 by 17-ethinylestradiol is due to interactions with isoleucine 89 on loop 1 Horm Mol Biol Clin Investig. 2014 Dec;20(3):81-90. doi: 10.1515/hmbci-2014-0028.

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