Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR0007)
Drug Name
E-3A
Synonyms
Aerodiol; Altrad; Aquadiol; Bardiol; Climara; Corpagen; Dihydrofolliculin; Dihydromenformon; Dihydrotheelin; Dihydroxyestrin; Dimenformon; Diogyn; Diogynets; Divigel; Estrace; Estraderm TTS; Estroclim; Estrovite; Evorel; Femestral; Femogen; Follicyclin; Ginosedol; Gynergon; Gynoestryl; Lamdiol; Macrodiol; Oestergon; Oestradiol; Oestroglandol; Ovahormon; Ovasterol; Ovastevol; Ovocyclin; Perlatanol; Primofol; Profoliol; Syndiol; Trocosone; Vagifem; Vivelle; beta-Estradiol; cis-Estradiol; estradiol; estradiol-17beta; progynon; 17beta-Estradiol; 50-28-2
Indication Turner syndrome [ICD11: LD50] Phase 3 [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 272.4 Topological Polar Surface Area 40.5
Heavy Atom Count 20 Rotatable Bond Count 0
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 2
Cross-matching ID
PubChem CID
5757
PubChem SID
2384 ; 4202 ; 75249 ; 652955 ; 820385 ; 821147 ; 823461 ; 823615 ; 825708 ; 829421 ; 831023 ; 831024 ; 838509 ; 841780 ; 4266382 ; 7847173 ; 7887363 ; 8028360 ; 8139856 ; 8139865 ; 8143549 ; 8153534 ; 10321307 ; 11110639 ; 11120283 ; 11120771 ; 11121259 ; 11121708 ; 11122188 ; 11362819 ; 11364683 ; 11365381 ; 11367245 ; 11367943 ; 11369807 ; 11370869 ; 11370870 ; 11372848 ; 11373544 ; 11375407 ; 11376105 ; 11377970 ; 11466469 ; 11467589 ; 11486157 ; 12012600 ; 14799365 ; 14799367 ; 17389898 ; 17405066
ChEBI ID
ChEBI:16469
CAS Number
50-28-2
TTD Drug ID
D08QMX
Formula
C18H24O2
Canonical SMILES
CC12CCC3C(C1CCC2O)CCC4=C3C=CC(=C4)O
InChI
1S/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,19-20H,2,4,6-9H2,1H3/t14-,15-,16+,17+,18+/m1/s1
InChIKey
VOXZDWNPVJITMN-ZBRFXRBCSA-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
17-beta-estradiol 3-sulfate-17-(beta-D-glucuronide) DM000884
5281895
Unclear 1 [2]
17-beta-Estradiol glucuronide DM000881
66424
Unclear 1 [18] , [19]
17-beta-Estradiol-3-glucuronide DM000879
13783824
Unclear 1 [2]
17alpha-Estradiol-3-glucuronide DM000882
66651
Unclear 1 [2]
17beta-Estradiol-3,17-beta-sulfate DM000868
66430
Unclear 1 [4]
2-hydroxyestrone DM000871
440623
Oxidation - Aromatic hydroxylation 1 [10]
2-hydroxyestrone DM000871
440623
Oxidation - 2-hydroxylation 1 [20]
2-methoxy-17beta-estradiol 3-O-(beta-D-glucuronide) DM000880
443076
Unclear 1 [18]
2-Methoxyestrone 3-glucuronide DM000878
22833612
Unclear 1 [20]
4-hydroxyestradiol DM000873
5282360
Unclear 1 [10]
4-hydroxyestrone DM000876
53477797
Oxidation - 4-hydroxylation 1 [10]
Estradiol-17alpha 3-D-glucuronoside DM000883
11988264
Unclear 1 [2]
Estradiol-17beta 3-sulfate DM000877
53477783
Unclear 1 [21]
Estrone DM003062
5870
Unclear 1 [10]
2-hydroxyestradiol DM000875
247304
Unclear 2 [2]
2-methoxyestrone DM000872
440624
Unclear 2 [22]
4-hydroxyestradiol DM000873
5282360
Unclear 2 [22]
4-methoxyestradiol DM000874
68578
Unclear 2 [10]
Estrone DM003062
5870
Unclear 2 [4]
Estrone sulfate DM003063
3001028
Unclear 2 [10]
16-alpha hydroxyestrone DM000869
115116
Unclear 3 [4]
17-Epiestriol DM000870
256737
Unclear 4 [4]
Estriol DM003060
5756
Unclear 4 [4]
⏷ Show the Full List of 23  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR013308 E-3A 17beta-Estradiol-3,17-beta-sulfate Unclear Unclear [4]
MR013313 E-3A 2-hydroxyestrone Oxidation - 2-hydroxylation CYP1A2 ... [20]
MR013315 E-3A 4-hydroxyestrone Oxidation - 4-hydroxylation CYP3A5 ... [10]
MR013318 E-3A 4-Hydroxyestradiol Unclear CYP1B1 [10]
MR013320 E-3A Estrone Unclear HSD17B2 [10]
MR013322 E-3A Estradiol-17beta 3-sulfate Unclear UGT [21]
MR013323 E-3A 2-Methoxyestrone 3-glucuronide Unclear UGT [20]
MR013324 E-3A 17-beta-Estradiol-3-glucuronide Unclear Unclear [2]
MR013325 E-3A 2-methoxy-17beta-estradiol 3-O-(beta-D-glucuronide) Unclear Unclear [18]
MR013326 E-3A 17-beta-Estradiol glucuronide Unclear Unclear [18], [19]
MR013327 E-3A 17alpha-Estradiol-3-glucuronide Unclear UGT [2]
MR013328 E-3A Estradiol-17alpha 3-D-glucuronoside Unclear UGT [2]
MR013329 E-3A 17-beta-estradiol 3-sulfate-17-(beta-D-glucuronide) Unclear UGT [2]
MR013309 17Beta-Estradiol-3,17-beta-sulfate Estrone Unclear Unclear [4]
MR013314 2-hydroxyestrone 2-hydroxyestradiol Unclear COMT [2]
MR013317 2-hydroxyestrone 2-methoxyestrone Unclear Unclear [22]
MR013319 4-Hydroxyestradiol 4-methoxyestradiol Unclear COMT [10]
MR013316 4-hydroxyestrone 4-Hydroxyestradiol Unclear Unclear [22]
MR013321 Estrone Estrone sulfate Unclear SULT [10]
MR013310 Estrone 16-alpha hydroxyestrone Unclear Unclear [4]
MR013311 16-alpha hydroxyestrone 17-Epiestriol Unclear Unclear [4]
MR013312 16-alpha hydroxyestrone Estriol Unclear Unclear [4]
⏷ Show the Full List of 22 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Catechol O-methyltransferase (COMT) DME0043 Homo sapiens
COMT_HUMAN
2.1.1.6
[2]
Cytochrome P450 1A1 (CYP1A1) DME0006 Homo sapiens
CP1A1_HUMAN
1.14.14.1
[3]
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[4]
Cytochrome P450 1B1 (CYP1B1) DME0023 Homo sapiens
CP1B1_HUMAN
1.14.14.1
[3]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[5]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[6]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[7]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[8]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[8]
Dehydrogenase/reductase retSDR3 (HSD17B14) DME0609 Homo sapiens
DHB14_HUMAN
1.1.1.62
[9]
Estradiol 17-beta-dehydrogenase 2 (HSD17B2) DME0422 Homo sapiens
DHB2_HUMAN
1.1.1.62
[10]
Farnesol dehydrogenase (AKR1B15) DME0399 Homo sapiens
AK1BF_HUMAN
1.1.1.54
[11]
Lactoperoxidase (LPO) DME0246 Homo sapiens
PERL_HUMAN
1.11.1.7
[12]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[13]
Sulfotransferase 1A1 (SULT1A1) DME0008 Homo sapiens
ST1A1_HUMAN
2.8.2.1
[14]
Thiopurine methyltransferase (TPMT) DME0014 Homo sapiens
TPMT_HUMAN
2.1.1.67
[15]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[16]
UDP-glucuronosyltransferase 2B28 (UGT2B28) DME0638 Homo sapiens
UDB28_HUMAN
2.4.1.17
[17]
⏷ Show the Full List of 18  DME(s)
Experimental Enzyme Kinetic Data of This Drug
DME Name DME Info Kinetic Data Uniprot ID REF
Farnesol dehydrogenase (AKR1B15) DME0399 Km = 0.0091 microM
AK1BF_HUMAN
[11]
References
1 ClinicalTrials.gov (NCT01710696) Induction of Puberty With 17-beta Estradiol in Girls With Turner Syndrome.
2 DrugBank(Pharmacology-Metabolism):E-3A
3 Cytochrome P450 isoforms catalyze formation of catechol estrogen quinones that react with DNA. Metabolism. 2007 Jul;56(7):887-94.
4 Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
5 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
6 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.
7 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
8 Drug Interactions Flockhart Table
9 Expression patterns of 17beta-hydroxysteroid dehydrogenase 14 in human tissues. Horm Metab Res. 2012 Dec;44(13):949-56.
10 Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Lett. 2005 Sep 28;227(2):115-24.
11 Aldo-keto Reductase 1B15 (AKR1B15): a mitochondrial human aldo-keto reductase with activity toward steroids and 3-keto-acyl-CoA conjugates. J Biol Chem. 2015 Mar 6;290(10):6531-45.
12 The metabolism of 17 beta-estradiol by lactoperoxidase: a possible source of oxidative stress in breast cancer. Carcinogenesis. 1994 Nov;15(11):2637-43.
13 CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
14 Proposed role of the sulfotransferase/sulfatase pathway in modulating yolk steroid effects. Integr Comp Biol. 2008 Sep;48(3):419-27.
15 Influence of estradiol-17 beta and progesterone on catechol-O-methyltransferase and monoamine oxidase activities in uterine artery and myometrium of ovariectomized pigs. Arch Vet Pol. 1993;33(1-2):29-37.
16 Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
17 Isolation and characterization of the UGT2B28 cDNA encoding a novel human steroid conjugating UDP-glucuronosyltransferase. Biochemistry. 2001 Apr 3;40(13):3869-81.
18 The metabolism of estradiol; oral compared to intravenous administration J Steroid Biochem. 1985 Dec;23(6A):1065-70. doi: 10.1016/0022-4731(85)90068-8.
19 Profiling endogenous serum estrogen and estrogen-glucuronides by liquid chromatography-tandem mass spectrometry Anal Chem. 2009 Dec 15;81(24):10143-8. doi: 10.1021/ac9019126.
20 DrugBank(Pharmacology-Metabolism)Estradiol acetate
21 FOODB:E-3A
22 Cytochromes P450: a structure-based summary of biotransformations using representative substrates Drug Metab Rev. 2008;40(1):1-100. doi: 10.1080/03602530802309742.

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