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

General Information of Drug (ID: DR1529)
Drug Name
Tamoxifen citrate
Synonyms
Tafoxen; Tamax; Tamofen; Tamoplex; Tamox-Puren; Tamoxasta; Tamoxifen (Citrate); Tamoxifen Citrate (Nolvadex); Tamoxifen citrate; Tamoxifen citrate salt; Tamoxifen citrate, 98%; Taxus; Terimon; UNII-7FRV7310N6; Z-Tamoxifen citrate; Zemide; Zitazonium; Zynoplex; Tamizam; Tamoxen; Tamoxifen (Z); Tamoxifen [INN:BAN]; Tamoxifen and its salts; Tamoxifene; Tamoxifene [INN-French]; Tamoxifeno; Tamoxifeno [INN-Spanish]; Tamoxifenum; Tamoxifenum [INN-Latin]; UNII-094ZI81Y45; Valodex; tamoxifen; trans-Tamoxifen; 1-p-beta-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene; 10540-29-1; CCRIS 3275; CHEMBL83; Citofen; Crisafeno; Diemon; EINECS 234-118-0; HSDB 6782; ICI 47699; ICI-46474; Istubol; Oncomox; Retaxim; Soltamox; TRANS FORM OF TAMOXIFEN; 54965-24-1; 7FRV7310N6; CAS-54965-24-1; CCRIS 6718; DSSTox_CID_1301; DSSTox_GSID_21301; DSSTox_RID_76068; Emblon; Farmifeno; Genox; Ginarsan; ICI 46474; ICI 46474 citrate; Istubal; Jenoxifen; Ledertam; MFCD00058321; NCGC00024928-06; NSC180973; Nolgen; Noltam; Nourytan; Noxitem; Oncotam
Indication Breast cancer [ICD11: 2C60] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 563.6 Topological Polar Surface Area 145
Heavy Atom Count 41 Rotatable Bond Count 13
Hydrogen Bond Donor Count 4 Hydrogen Bond Acceptor Count 9
Cross-matching ID
PubChem CID
2733525
CAS Number
54965-24-1
TTD Drug ID
D07KSG
Formula
C32H37NO8
Canonical SMILES
CCC(=C(C1=CC=CC=C1)C2=CC=C(C=C2)OCCN(C)C)C3=CC=CC=C3.C(C(=O)O)C(CC(=O)O)(C(=O)O)O
InChI
1S/C26H29NO.C6H8O7/c1-4-25(21-11-7-5-8-12-21)26(22-13-9-6-10-14-22)23-15-17-24(18-16-23)28-20-19-27(2)3;7-3(8)1-6(13,5(11)12)2-4(9)10/h5-18H,4,19-20H2,1-3H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/b26-25-;
InChIKey
FQZYTYWMLGAPFJ-OQKDUQJOSA-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
4-hydroxytamoxifen DM000017
449459
Oxidation - 4-Hydroxylation 1 [3] , [4] , [19] , [20]
Alpha-hydroxytamoxifen DM000013
3036580
Oxidation - Hydroxylation 1 [21] , [20]
N-Desmethyltamoxifen DM000001
6378383
Oxidation - N-Dealkylation 1 [3] , [4] , [19] , [22] , [23]
Tamoxifen N-oxide DM000016
3033895
Oxidation - N-Oxidation 1 [4] , [20] , [24]
4-hydroxytamoxifen sulfate DM000009
131770034
Conjugation - Sulfation 2 [2]
Alpha-tamoxifen sulfate DM000014 N. A. Conjugation - Sulfation 2 [2]
Cis-4-hydroxytamoxifen-O-glucuronide DM000015
131770036
Conjugation - Sulfation 2 [2]
Endoxifen DM000007
10090750
Conjugation - Sulfation 2 [2]
Endoxifen DM000007
10090750
Oxidation - 4-Hydroxylation 2 [2]
N,N-didesmethyltamoxifen DM000002
3036172
Unclear 2 [2]
N-desmethyltamoxifen sulfate DM000012 N. A. Conjugation - Sulfation 2 [2]
Tamoxifen glucuronides DM000011 N. A. Conjugation - Glucuronidation 2 [2]
4-endoxifen sulfate DM000010 N. A. Conjugation - Sulfation 3 [2]
4-hydroxytamoxifen sulfate DM000009
131770034
Conjugation - Sulfation 3 [2]
Endoxifen DM000007
10090750
Conjugation - Sulfation 3 [2]
Norendoxifen DM000008
68037237
Oxidation - Demethylation 3 [2]
Tamoxifen glucuronides DM000011 N. A. Conjugation - Glucuronidation 3 [2]
Tamoxifen metabolite Y DM000003
3033897
Unclear 3 [2]
4-endoxifen sulfate DM000010 N. A. Conjugation - Sulfation 4 [2]
4-hydroxytamoxifen sulfate DM000009
131770034
Conjugation - Sulfation 4 [2]
Norendoxifen DM000008
68037237
Oxidation - Demethylation 4 [2]
Tamoxifen glucuronides DM000011 N. A. Conjugation - Glucuronidation 4 [2]
Tamoxifen metabolite E DM000004
3033896
Oxidation - Ether Cleavage 4 [2]
Tamoxifen metabolite E glucuronide DM000006 N. A. Conjugation - O-Glucuronidation 5 [2]
Tamoxifen metabolite E sulfate conjugate DM000005 N. A. Conjugation - Sulfation 5 [2]
⏷ Show the Full List of 25  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR003510 Tamoxifen citrate N-Desmethyltamoxifen Oxidation - N-Dealkylation CYP2D6 ... [3], [4], [19], [22], [23]
MR003522 Tamoxifen citrate Alpha-hydroxytamoxifen Oxidation - Hydroxylation Unclear [21], [20]
MR003525 Tamoxifen citrate Tamoxifen N-oxide Oxidation - N-Oxidation FMO1 ... [4], [20], [24]
MR003526 Tamoxifen citrate 4-hydroxytamoxifen Oxidation - 4-Hydroxylation CYP2D6 ... [3], [4], [19], [20]
MR003527 4-hydroxytamoxifen Tamoxifen glucuronides Conjugation - Glucuronidation UGT1A8 ... [2]
MR003528 4-hydroxytamoxifen 4-hydroxytamoxifen sulfate Conjugation - Sulfation SULT1A1 ... [2]
MR003530 4-hydroxytamoxifen Endoxifen Conjugation - Sulfation CYP3A5 ... [2]
MR003523 Alpha-hydroxytamoxifen Alpha-tamoxifen sulfate Conjugation - Sulfation SULT1A2 [2]
MR003524 Alpha-hydroxytamoxifen Alpha-hydroxytamoxifen glucuronide Conjugation - Sulfation Unclear [2]
MR003511 N-Desmethyltamoxifen N,N-didesmethyltamoxifen Unclear CYP3A5 ... [2]
MR003516 N-Desmethyltamoxifen Endoxifen Oxidation - 4-Hydroxylation CYP2D6 [2]
MR003521 N-Desmethyltamoxifen N-desmethyltamoxifen sulfate Conjugation - Sulfation Unclear [2]
MR003529 4-hydroxytamoxifen sulfate Endoxifen Conjugation - Sulfation SULT1A1 ... [2]
MR003517 Endoxifen Norendoxifen Oxidation - Demethylation Unclear [2]
MR003518 Endoxifen 4-hydroxytamoxifen sulfate Conjugation - Sulfation SULT1A1 ... [2]
MR003519 Endoxifen 4-endoxifen sulfate Conjugation - Sulfation SULT2A1 [2]
MR003520 Endoxifen Tamoxifen glucuronides Conjugation - Glucuronidation UGT1A8 ... [2]
MR003512 N,N-didesmethyltamoxifen Tamoxifen metabolite Y Unclear CYP3A5 [2]
MR003513 Tamoxifen metabolite Y Tamoxifen metabolite E Oxidation - Ether Cleavage CYP3A5 [2]
MR003514 Tamoxifen metabolite E Tamoxifen metabolite E sulfate conjugate Conjugation - Sulfation SULT1A1 ... [2]
MR003515 Tamoxifen metabolite E Tamoxifen metabolite E glucuronide Conjugation - O-Glucuronidation ADA [2]
⏷ Show the Full List of 21 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Adenosine aminohydrolase (ADA) DME0060 Homo sapiens
ADA_HUMAN
3.5.4.4
[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
[5]
Cytochrome P450 2A6 (CYP2A6) DME0005 Homo sapiens
CP2A6_HUMAN
1.14.14.1
[6]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[7]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[8]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[9]
Cytochrome P450 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[6]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[10]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[11]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[12]
Dimethylaniline oxidase 1 (FMO1) DME0059 Homo sapiens
FMO1_HUMAN
1.14.13.8
[13]
Dimethylaniline oxidase 3 (FMO3) DME0039 Homo sapiens
FMO3_HUMAN
1.14.13.8
[13]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[14]
Sulfotransferase 1A1 (SULT1A1) DME0008 Homo sapiens
ST1A1_HUMAN
2.8.2.1
[15]
Sulfotransferase 1A2 (SULT1A2) DME0062 Homo sapiens
ST1A2_HUMAN
2.8.2.1
[2]
Sulfotransferase 1E1 (SULT1E1) DME0061 Homo sapiens
ST1E1_HUMAN
2.8.2.4
[2]
Sulfotransferase 2A1 (SULT2A1) DME0074 Homo sapiens
ST2A1_HUMAN
2.8.2.14
[2]
Thiopurine methyltransferase (TPMT) DME0014 Homo sapiens
TPMT_HUMAN
2.1.1.67
[16]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[17]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DME0075 Homo sapiens
UD110_HUMAN
2.4.1.17
[18]
UDP-glucuronosyltransferase 1A8 (UGT1A8) DME0064 Homo sapiens
UD18_HUMAN
2.4.1.17
[2]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[19]
⏷ Show the Full List of 24  DME(s)
References
1 Tamoxifen Citrate was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 PharmGKB:Tamoxifen citrate
3 Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002 Aug;30(8):869-74.
4 Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
5 Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen Drug Metab Dispos. 2002 Aug;30(8):869-74. doi: 10.1124/dmd.30.8.869.
6 Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
7 Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6. J Pharmacol Exp Ther. 2002 Jun;301(3):945-52.
8 Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
9 CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
10 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.
11 Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
12 Drug Interactions Flockhart Table
13 Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1) Drug Metab Dispos. 2014 Nov;42(11):1843-50. doi: 10.1124/dmd.114.059709.
14 Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
15 Tamoxifen-induced adduct formation and cell stress in human endometrial glands. Drug Metab Dispos. 2010 Jan;38(1):200-7.
16 Polymorphism of estrogen metabolism genes and cataract. Med Hypotheses. 2004;63(3):494-7.
17 Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
18 Glucuronidation of active tamoxifen metabolites by the human UDP glucuronosyltransferases. Drug Metab Dispos. 2007 Nov;35(11):2006-14.
19 Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22.
20 The tamoxifen dilemma. Carcinogenesis. 1999 Jul;20(7):1153-60.
21 [Effect of lithium on the hematopoietic stem cells] Acta Haematol Pol. 1989 Jan-Jun;20(1):99-106.
22 Identification and biological activity of tamoxifen metabolites in human serum Biochem Pharmacol. 1983 Jul 1;32(13):2045-52. doi: 10.1016/0006-2952(83)90425-2.
23 PharmGKB summary: tamoxifen pathway, pharmacokinetics Pharmacogenet Genomics. 2013 Nov;23(11):643-7. doi: 10.1097/FPC.0b013e3283656bc1.
24 Oxidation of tamoxifen by human flavin-containing monooxygenase (FMO) 1 and FMO3 to tamoxifen-N-oxide and its novel reduction back to tamoxifen by human cytochromes P450 and hemoglobin Drug Metab Dispos. 2005 Oct;33(10):1446-52. doi: 10.1124/dmd.104.000802.

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