Palifosfamide

Palifosfamide is a novel DNA alkylator and the active metabolite of ifosfamide, with antitumor activity.
Isophosphamide mustard is a phosphorodiamide.|Palifosfamide (ZIO-201) is a proprietary stabilized metabolite of ifosfamide. Ifosfamide has been shown to be effective in high doses in treating testicular cancer, sarcoma and lymphoma.|Palifosfamide is a synthetic mustard compound with potential antineoplastic activity. An active metabolite of ifosfamide covalently linked to the amino acid lysine for stability, palifosfamide irreversibly alkylates and cross-links DNA through GC base pairs, resulting in irreparable 7-atom inter-strand cross-links; inhibition of DNA replication and cell death follow. Unlike ifosfamide, this agent is not metabolized to acrolein or chloroacetaldehyde, metabolites associated with bladder and CNS toxicities. In addition, because palifosfamide does not require activation by aldehyde dehydrogenase, it may overcome the tumor resistance seen with ifosfamide.
Palifosfamide is an active metabolite of the DNA alkylating agent ifosfamide. It is formed through hydroxylation of ifosfamide by various hepatic cytochrome P450 (CYP) isoforms. It is cytotoxic to L1210 and CCRF-CEM cancer cells when used at a concentration of 100 μM. Palifosfamide (100 mg/kg per day) reduces tumor growth in murine Lewis lung carcinoma and L1210 leukemia models, as well as a rat Yoshida ascitic sarcoma model.
ChEBI: Palifosfamide, also known as Isophosphamide mustard, is a type of phosphorodiamide. It is a proprietary stabilized metabolite of ifosfamide. Ifosfamide has been shown to be effective in high doses in treating testicular cancer, sarcoma and lymphoma.