General Information of Drug (ID: DR0855)
Drug Name
Ifosfamide
Prodrug Info Ifosfamide is the prodrug of 4-Hydroxyifosfamide
Synonyms
Ifosfamid; Ifosfamida; Ifosfamida [INN-Spanish]; Ifosfamide Sterile; Ifosfamidum; Ifosfamidum [INN-Latin]; Ifosphamide; Ifsofamide; Iphosphamid; Iphosphamide; Isoendoxan; Isofosfamide; Isophosphamide; MJF 9325; MJF-9325; Mitoxana; Naxamide; ASTA Z 4942; Holoxan; Holoxan 1000; I-Phosphamide; Z 4942; Z-4942; ifomide; ifosfamide; isosfamide; 2H-1,3,2-Oxazaphosphorin-2-amine, N,3-bis(2-chloroethyl)tetrahydro-, 2-oxide; 3778-73-2; A 4942; CCRIS 352; Cyfos; Ifex; NCI-C01638; NSC 109724; NSC-109724; NSC109724; UNII-UM20QQM95Y; Z4942
Indication Lung cancer [ICD11: 2C25] 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
3690
PubChem SID
9259 ; 222385 ; 301170 ; 4725775 ; 7847409 ; 7979588 ; 8152333 ; 11112546 ; 11404628 ; 11466861 ; 11467981 ; 11486442 ; 14823762 ; 29222813 ; 46508335 ; 47440513 ; 47662533 ; 47811010 ; 47959991 ; 48413921 ; 48423569 ; 49699179 ; 49854327 ; 50000801 ; 50124150 ; 53789434 ; 56313681 ; 56463644 ; 57321943 ; 79550110 ; 85174241 ; 87350409 ; 92125751 ; 92308097 ; 92309248 ; 92717658 ; 99418082 ; 99437241 ; 103274495 ; 103914488 ; 104304241 ; 118043408 ; 119526434 ; 121363422 ; 124757155 ; 124800304 ; 124893609 ; 124893610 ; 125163959 ; 125349289
ChEBI ID
CHEBI:5864
CAS Number
3778-73-2
TTD Drug ID
D02TLO
Formula
C7H15Cl2N2O2P
Canonical SMILES
C1CN(P(=O)(OC1)NCCCl)CCCl
InChI
1S/C7H15Cl2N2O2P/c8-2-4-10-14(12)11(6-3-9)5-1-7-13-14/h1-7H2,(H,10,12)
InChIKey
HOMGKSMUEGBAAB-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-Hydroxyifosfamide DM004293
308171
Oxidation - 4-hydroxylation 1 [10]
Chloroacetaldehyde DM003749
33
Unclear 1 [10] , [11]
Dechloroethyl cyclophosphamide DM003748
114861
Unclear 1 [12] , [10]
Dechloroethylifosfamide DM004303
119105
Unclear 1 [10]
2-chloroethanol DM004301
34
Oxidation - Oxidationn 2 [2]
4-Ketoifosfamide DM004299
99303
Unclear 2 [10]
4-Thioifosfamide DM004300 N. A. Conjugation - Glutathione conjugation 2 [8]
Aldoifosfamide DM004294
189733
Unclear 2 [8]
Acrolein DM003742
7847
Unclear 3 [10]
Alcoifosfamide DM004298
10265589
Unclear 3 [8]
Carboxylifosfamide DM004297
124143
Unclear 3 [8]
Isophosphamide mustard DM004295
100427
Unclear 3 [2]
Acrylic Acid DM003743
6581
Unclear 4 [2]
Ifosforamide Aziridinium DM004296
165361861
Unclear 4 [2]
⏷ 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
MR004650 Ifosfamide 4-Hydroxyifosfamide Oxidation - 4-hydroxylation PTGS1 ... [10]
MR004660 Ifosfamide Chloroacetaldehyde Unclear CYP3A4 ... [10], [11]
MR004662 Ifosfamide 3-Dechloroethylifosfamide Unclear CYP3A4 ... [12], [10]
MR004663 Ifosfamide Dechloroethylifosfamide Unclear CYP3A4 ... [10]
MR004651 4-Hydroxyifosfamide Aldoifosfamide Unclear Unclear [8]
MR004658 4-Hydroxyifosfamide 4-Ketoifosfamide Unclear Unclear [10]
MR004659 4-Hydroxyifosfamide 4-Thioifosfamide Conjugation - Glutathione conjugation Unclear [8]
MR004661 Chloroacetaldehyde 2-chloroethanol Oxidation - Oxidationn CYP2E1 [2]
MR004652 Aldoifosfamide Isophosphamide mustard Unclear Unclear [2]
MR004654 Aldoifosfamide Acrolein Unclear Unclear [10]
MR004656 Aldoifosfamide Carboxylifosfamide Unclear Unclear [8]
MR004657 Aldoifosfamide Alcoifosfamide Unclear Unclear [8]
MR004655 Acrolein Acrylic Acid Unclear RDH11 ... [2]
MR004653 Isophosphamide mustard Ifosforamide Aziridinium Unclear Unclear [2]
⏷ 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
Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) DMEN405 Homo sapiens
AL3A1_HUMAN
1.2.1.5
[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
[5]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[6]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[7]
Cytochrome P450 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[8]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[6]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[9]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[5]
Prostaglandin G/H synthase 1 (COX-1) DME0091 Homo sapiens
PGH1_HUMAN
1.14.99.1
[8]
Prostaglandin G/H synthase 1 (COX-1) DME0091 Homo sapiens
PGH1_HUMAN
1.14.99.1
[10]
Retinol dehydrogenase 11 (RDH11) DMEN404 Homo sapiens
RDH11_HUMAN
1.1.1.300
[2]
⏷ Show the Full List of 14  DME(s)
References
1 Ifosfamide was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 DrugBank(Pharmacology-Metabolism):Ifosfamide
3 Measurement of 4-hydroxylation of ifosfamide in human liver microsomes using the estimation of free and protein-bound acrolein and codetermination of keto- and carboxyifosfamide. J Cancer Res Clin Oncol. 2002 Jul;128(7):385-92.
4 A novel distal enhancer module regulated by pregnane X receptor/constitutive androstane receptor is essential for the maximal induction of CYP2B6 gene expression. J Biol Chem. 2003 Apr 18;278(16):14146-52.
5 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.
6 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.
7 CYP2C9 polymorphisms in human tumors. Anticancer Res. 2006 Jan-Feb;26(1A):299-305.
8 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.
9 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
10 The KEGG resource for deciphering the genome
11 2-Chloroacetaldehyde-induced cerebral glutathione depletion and neurotoxicity
12 Pharmacogenomics knowledge for personalized medicine Clin Pharmacol Ther. 2012 Oct;92(4):414-7. doi: 10.1038/clpt.2012.96.

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