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

General Information of Drug (ID: DR0546)
Drug Name
Doxorubicin
Synonyms
Doxorubicin [USAN:INN:BAN]; Doxorubicina; Doxorubicina [INN-Spanish]; Doxorubicine; Doxorubicine [INN-French]; Doxorubicinum; Doxorubicinum [INN-Latin]; Adriablastin; Adriamycin; Adriamycin semiquinone; FI 106; Myocet; doxorubicin; 14-Hydroxydaunomycin; 14-Hydroxydaunorubicine; 23214-92-8; CCRIS 739; CHEBI:28748; CHEMBL53463; Doxil; EINECS 245-495-6; HSDB 3070; NCI-C01514; NDC 38242-874; UNII-80168379AG
Indication Breast cancer [ICD11: 2C60] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 543.5 Topological Polar Surface Area 206
Heavy Atom Count 39 Rotatable Bond Count 5
Hydrogen Bond Donor Count 6 Hydrogen Bond Acceptor Count 12
Cross-matching ID
PubChem CID
31703
PubChem SID
4809 ; 596007 ; 7887074 ; 7979129 ; 8172352 ; 11466466 ; 11467586 ; 11486131 ; 11533222 ; 11538021 ; 14910387 ; 14910388 ; 17397983 ; 24769891 ; 26704333 ; 26709766 ; 34673809 ; 46507641 ; 47440542 ; 47515588 ; 47589229 ; 47736754 ; 47811027 ; 47811028 ; 48035406 ; 48185239 ; 48414671 ; 48415928 ; 49698493 ; 49846798 ; 49855190 ; 50063935 ; 53787595 ; 53837797 ; 56310844 ; 56311108 ; 56311939 ; 56312034 ; 56312063 ; 56312270 ; 56312524 ; 56312768 ; 56313130 ; 56313308 ; 56313325 ; 56313365 ; 56313675 ; 56313990 ; 56314080 ; 56314176
ChEBI ID
ChEBI:28748
CAS Number
23214-92-8
TTD Drug ID
D07VLY
Formula
C27H29NO11
Canonical SMILES
CC1C(C(CC(O1)OC2CC(CC3=C2C(=C4C(=C3O)C(=O)C5=C(C4=O)C(=CC=C5)OC)O)(C(=O)CO)O)N)O
InChI
1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15-,17-,22+,27-/m0/s1
InChIKey
AOJJSUZBOXZQNB-TZSSRYMLSA-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
7-deoxydaxorubicinol DM001715
45038813
Unclear 1 [3]
7-deoxydoxorubicinolone DM006225
3081104
Unclear 1 [16]
Doxorubicin-semiquinone DM001716
131769966
Unclear 1 [3]
Doxorubicine hydroxyaglycone DM006224 N. A. Unclear 1 [3]
Doxorubicinol DM001717
83970
Unclear 1 [3]
Doxirubicinol hydroxyaglycone DM001714
10476988
Unclear 2 [3]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR006673 Doxorubicin Doxorubicine hydroxyaglycone Unclear Unclear [3]
MR006675 Doxorubicin Doxorubicinol Unclear CBR1 ... [3]
MR006676 Doxorubicin Doxorubicin-semiquinone Unclear NQO1 ... [3]
MR006677 Doxorubicin Doxorubicinol deoxaglycone Unclear POR ... [3]
MR006678 Doxorubicin 7-deoxydoxorubicinolone Unclear Unclear [16]
MR006674 Doxorubicine hydroxyaglycone Doxirubicinol hydroxyaglycone Unclear Unclear [3]
⏷ Show the Full List of 6 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Aldo-keto reductase 1A1 (AKR1A1) DME0098 Homo sapiens
AK1A1_HUMAN
1.1.1.2
[2]
Aldo-keto reductase 1A1 (AKR1A1) DME0098 Homo sapiens
AK1A1_HUMAN
1.1.1.2
[3]
Aldo-keto reductase 1C3 (AKR1C3) DME0118 Homo sapiens
AK1C3_HUMAN
1.1.1.357
[4]
Aldo-keto reductase 1C3 (AKR1C3) DME0118 Homo sapiens
AK1C3_HUMAN
1.1.1.357
[3]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[5]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[6]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[7]
Methionine synthase reductase (MTRR) DME0431 Homo sapiens
MTRR_HUMAN
1.16.1.8
[8]
Molybdopterin-dependent enzyme (molD) DME1039 Klebsiella pneumoniae
A0A327SQQ7_9ACTN
1.1.1.40
[9]
Molybdopterin-dependent enzyme (molD) DME1040 Raoultella planticola
A0A327U7N1_9ACTN
1.1.1.40
[9]
Molybdopterin-dependent enzyme (molD) DME1422 Escherichia coli
A0A327UAE0_9ACTN
1.1.1.40
[9]
NADH dehydrogenase (nuoE) DME1041 Streptomyces griseus
J9VB37_9ACTN
1.6.5.11
[10]
NADH-ubiquinone oxidoreductase 20 kDa (NDUFS7) DME0121 Homo sapiens
NDUS7_HUMAN
7.1.1.2
[11]
NADH-ubiquinone oxidoreductase 30 kDa (NDUFS3) DME0120 Homo sapiens
NDUS3_HUMAN
7.1.1.2
[11]
NADH-ubiquinone oxidoreductase 49 kDa (NDUFS2) DME0119 Homo sapiens
NDUS2_HUMAN
7.1.1.2
[11]
NADH-ubiquinone oxidoreductase 49 kDa (NDUFS2) DME0119 Homo sapiens
NDUS2_HUMAN
7.1.1.2
[3]
NADPH-cytochrome P450 reductase (CPR) DME0076 Homo sapiens
NCPR_HUMAN
1.6.2.4
[12]
NADPH-cytochrome P450 reductase (CPR) DME0076 Homo sapiens
NCPR_HUMAN
1.6.2.4
[3]
NADPH-dependent carbonyl reductase 1 (CBR1) DME0067 Homo sapiens
CBR1_HUMAN
1.1.1.184
[3]
NADPH-dependent carbonyl reductase 3 (CBR3) DME0068 Homo sapiens
CBR3_HUMAN
1.1.1.184
[3]
Nitric oxide synthase brain (NOS1) DME0122 Homo sapiens
NOS1_HUMAN
1.14.13.39
[13]
Nitric oxide synthase brain (NOS1) DME0122 Homo sapiens
NOS1_HUMAN
1.14.13.39
[3]
Nitric oxide synthase endothelial (NOS3) DME0123 Homo sapiens
NOS3_HUMAN
1.14.13.39
[13]
Nitric oxide synthase endothelial (NOS3) DME0123 Homo sapiens
NOS3_HUMAN
1.14.13.39
[3]
Nitric oxide synthase inducible (NOS2) DME0124 Homo sapiens
NOS2_HUMAN
1.14.13.39
[13]
Nitric oxide synthase inducible (NOS2) DME0124 Homo sapiens
NOS2_HUMAN
1.14.13.39
[3]
Quinone reductase 1 (NQO1) DME0097 Homo sapiens
NQO1_HUMAN
1.6.5.2
[11]
Quinone reductase 1 (NQO1) DME0097 Homo sapiens
NQO1_HUMAN
1.6.5.2
[3]
Succinic semialdehyde reductase (AKR7A2) DME0234 Homo sapiens
ARK72_HUMAN
1.1.1.B47
[14]
Unclear metabolic mechanism (DME-unclear) DME1265 Escherichia coli Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1274 Klebsiella pneumoniae Not Available Not Available [9]
Unclear metabolic mechanism (DME-unclear) DME1455 Raoultella planticola Not Available Not Available [9]
Xanthine dehydrogenase/oxidase (XDH) DME0070 Homo sapiens
XDH_HUMAN
1.17.1.4
[15]
Xanthine dehydrogenase/oxidase (XDH) DME0070 Homo sapiens
XDH_HUMAN
1.17.1.4
[3]
⏷ Show the Full List of 34  DME(s)
Experimental Enzyme Kinetic Data of This Drug
DME Name DME Info Kinetic Data Uniprot ID REF
Methionine synthase reductase (MTRR) DME0431 Km = 0.0286 microM
MTRR_HUMAN
[8]
References
1 Doxorubicin was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20.
3 PharmGKB:Doxorubicin
4 Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto reductase (AKR) 1C3. Toxicol Lett. 2008 Sep;181(1):1-6.
5 Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
6 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.
7 Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
8 Differences in the efficiency of reductive activation of methionine synthase and exogenous electron acceptors between the common polymorphic variants of human methionine synthase reductase. Biochemistry. 2002 Nov 12;41(45):13378-85.
9 Transformation of the anticancer drug doxorubicin in the human gut microbiome. ACS Infect Dis. 2018 Jan 12;4(1):68-76.
10 Bacterial inactivation of the anticancer drug doxorubicin. Chem Biol. 2012 Oct 26;19(10):1255-64.
11 Differential ability of cytostatics from anthraquinone group to generate free radicals in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase, and xanthine oxidase. Oncol Res. 2003;13(5):245-52.
12 Kinetics of anthracycline antibiotic free radical formation and reductive glycosidase activity. Arch Biochem Biophys. 1983 May;223(1):68-75.
13 The role of nitric oxide in anthracycline toxicity and prospects for pharmacologic prevention of cardiac damage. FASEB J. 2004 Apr;18(6):664-75.
14 Naturally occurring variants of human aldo-keto reductases with reduced in vitro metabolism of daunorubicin and doxorubicin. J Pharmacol Exp Ther. 2010 Dec;335(3):533-45.
15 Xanthine oxidoreductase in drug metabolism: beyond a role as a detoxifying enzyme. Curr Med Chem. 2016;23(35):4027-4036.
16 Pharmacokinetics and metabolism of doxorubicin after short-term infusions in lymphoma patients

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