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

General Information of Drug (ID: DR0391)
Drug Name
Cyclophosphamide
Prodrug Info Cyclophosphamide is the prodrug of Phosphoramide Mustard
Synonyms
Ciclofosfamida; Ciclophosphamide; Clafen; Claphene; Cyclofosphamide; Cyclophosphamid; Cyclophosphamide anhydrous; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclophosphoramide; Cyclostin; Cyklofosfamid; Cytophosphan; Cytophosphane; Cytoxan; Endoxan; Endoxan R; Endoxan-Asta; Endoxana; Endoxanal; Endoxane; Enduxan; Genoxal; Lyophilized Cytoxan; Mitoxan; Neosar; Procytox; Rcra waste number U058; Semdoxan; Sendoxan; Senduxan; Zyklophosphamid; cyclophosphamide; (+-)-Cyclophosphamide; (RS)-Cyclophosphamide; 50-18-0
Indication Multiple myeloma [ICD11: 2A83] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 261.079 Topological Polar Surface Area 41.6
Heavy Atom Count 14 Rotatable Bond Count 5
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 4
Cross-matching ID
PubChem CID
2907
PubChem SID
10090 ; 87150 ; 141705 ; 141706 ; 598053 ; 5080187 ; 7979009 ; 8151862 ; 10524283 ; 11110909 ; 11335421 ; 11360660 ; 11363752 ; 11366314 ; 11368876 ; 11371419 ; 11374027 ; 11377038 ; 11406490 ; 11461632 ; 11484807 ; 11488962 ; 11490186 ; 11492119 ; 11494672 ; 11533313 ; 14848034 ; 17404801 ; 25765844 ; 29222060 ; 46505441 ; 47365072 ; 47440141 ; 47515205 ; 48334372 ; 48413505 ; 48415829 ; 48423195 ; 49855451 ; 50000789 ; 50105634 ; 50105635 ; 51092052 ; 53777344 ; 53788477 ; 56310899 ; 56311422 ; 56313326 ; 56313987 ; 57288588
ChEBI ID
CHEBI:3996
CAS Number
6055-19-2
TTD Drug ID
D0CT9C
Formula
C7H15Cl2N2O2P
Canonical SMILES
C1CNP(=O)(OC1)N(CCCl)CCCl
InChI
1S/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12)
InChIKey
CMSMOCZEIVJLDB-UHFFFAOYSA-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-Hydroxycyclophosphamide DM003738
99735
Unclear - Unclear 1 [11]
Dechloroethyl cyclophosphamide DM003748
114861
Unclear - Unclear 1 [2]
4-Ketocyclophosphamide DM003747
33676
Unclear - Unclear 2 [2]
Aldophosphamide DM003739
107744
Unclear - Unclear 2 [2]
Acrolein DM003742
7847
Unclear - Unclear 3 [2]
Carboxyphosphamide DM003744
31515
Unclear - Unclear 3 [2]
Phosphoramide Mustard DM003740
96356
Unclear - Unclear 3 [2]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR009942 Cyclophosphamide 4-Hydroxycyclophosphamide Unclear - Unclear CYP3A4 ... [11]
MR009948 Cyclophosphamide Dechloroethyl cyclophosphamide Unclear - Unclear CYP3A4 [2]
MR009943 4-Hydroxycyclophosphamide Aldophosphamide Unclear - Unclear Unclear [2]
MR009947 4-Hydroxycyclophosphamide 4-Ketocyclophosphamide Unclear - Unclear ALDH [2]
MR009944 Aldophosphamide Phosphamide mustard Unclear - Unclear CYP [2]
MR009945 Aldophosphamide Carboxyphosphamide Unclear - Unclear ALDH [2]
MR009946 Aldophosphamide Acrolein Unclear - Unclear Unclear [2]
⏷ Show the Full List of 7 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Aldehyde dehydrogenase (ALDH) DMEN076 . Not Available Not Available [2]
Cytochrome P450 2A6 (CYP2A6) DME0005 Homo sapiens
CP2A6_HUMAN
1.14.14.1
[3]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[4]
Cytochrome P450 2C18 (CYP2C18) DME0017 Homo sapiens
CP2CI_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 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[8]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[9]
Unclear metabolic mechanism (DME-unclear) DME1251 Bacteroides fragilis Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1357 Alistipes indistinctus Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1393 Blautia hansenii Not Available Not Available [10]
Unclear metabolic mechanism (DME-unclear) DME1431 Holdemanella biformis Not Available Not Available [10]
⏷ Show the Full List of 13  DME(s)
References
1 Cyclophosphamide was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 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.
3 Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos. 1999 Jun;27(6):655-66.
4 The effect of cyclophosphamide with and without dexamethasone on cytochrome P450 3A4 and 2B6 in human hepatocytes. Drug Metab Dispos. 2002 Jul;30(7):814-22.
5 Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines. Cancer Res. 1997 May 15;57(10):1946-54.
6 CYP2C9 polymorphisms in human tumors. Anticancer Res. 2006 Jan-Feb;26(1A):299-305.
7 Effects of ketoconazole on cyclophosphamide metabolism: evaluation of CYP3A4 inhibition effect using the in vitro and in vivo models. Exp Anim. 2018 Feb 9;67(1):71-82.
8 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
9 Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
10 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
11 Aprepitant inhibits cyclophosphamide bioactivation and thiotepa metabolism

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