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Pathway Description
Ifosfamide Metabolism Pathway
Homo sapiens
Drug Metabolism Pathway
Created: 2013-09-11
Last Updated: 2019-08-30
Ifosfamide is an alkylating agent used in the treatment of certain cancers. Following absorption, ifosfamide is converted into 4-hydroxyifosfamide by a variety of cytochrome P450 isozymes in the liver. 4-Hydroxyifosfamide crosses the plasma membrane of the cancer cell and spontaneuosly forms aldoifosfamide. This is a reversible reaction. Aldoifosfamide can decompose into acrolein and ifosforamide mustard. Ifosforamide mustard is the active alkylating agent and forms alkyl adducts with DNA through an ifosforamide aziridinium intermediate. Alkylation of DNA causes DNA damage and ultimately cell death.
References
Ifosfamide Pathway References
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Pubmed: 15190123
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Pubmed: 3267210
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Pubmed: 8569713
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Pubmed: 7811260
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Pubmed: 2732228
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Pubmed: 9409631
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Pubmed: 2726448
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Pubmed: 2748347
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Pubmed: 19296407
Morgan CA, Hurley TD: Development of a high-throughput in vitro assay to identify selective inhibitors for human ALDH1A1. Chem Biol Interact. 2015 Jun 5;234:29-37. doi: 10.1016/j.cbi.2014.10.028. Epub 2014 Nov 4.
Pubmed: 25450233
Hsu LC, Chang WC, Yoshida A: Genomic structure of the human cytosolic aldehyde dehydrogenase gene. Genomics. 1989 Nov;5(4):857-65.
Pubmed: 2591967
Hsu LC, Chang WC, Shibuya A, Yoshida A: Human stomach aldehyde dehydrogenase cDNA and genomic cloning, primary structure, and expression in Escherichia coli. J Biol Chem. 1992 Feb 15;267(5):3030-7.
Pubmed: 1737758
Hsu LC, Yoshida A: Human stomach aldehyde dehydrogenase, ALDH3. Adv Exp Med Biol. 1993;328:141-52. doi: 10.1007/978-1-4615-2904-0_16.
Pubmed: 8493892
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