(Zymafos; ZIO-201) is a cytotoxic, active metabolite of the alkylating agent ifosfamide, which causes irreparable DNA interstrand cross-linking in cancer cells. This prevents DNA replication and cell division, leading to cell death.
In contrast to ifosfamide, palifosfamide is not metabolised to the toxins acrolein and chloracetaldehyde, which are associated with haemorrhagic cystitis, and neuro- and nephro-toxicities respectively. Also, palifosfamide is not a substrate for aldehyde dehydrogenase (ALDH), an important mediator of drug resistance
Cyclophosphamide and ifosfamide are nitrogen mustard alkylating agents that act by crosslinking DNA strands at the guanine N-7 position, resulting in cell death. Both of these are prodrugs that are metabolised in the liver to phosphoramide mustard active metabolites, but their use is limited by toxic side-effects. They are also prone to tumour resistance, which results from numerous mechanisms, including DNA repair.
In an attempt to overcome some of these problems, Ziopharm Oncology has developed palifosfamide tromethamine…
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