Ifosfamide (IF) is a widely used antitumor prodrug. It is in the oxazaphosphorine class of alkylating agents, and it is effective against solid tumors. Ifosfamide mechanism of crosslinking DNA plays a major role in preventing cancer cells from proliferating. Ifosfamide is approved by FDA for the treatment of germ cell testicular cancer.

Palifosfamide or ZIO-201 (isophosphoramide mustard; IPM), a bi-functional DNA alkylator, is the active metabolite of ifosfamide (IFOS). IFOS and the related drug cyclophosphamide (CPA) are widely used anti-cancer drugs. Both are pro-drugs and need to be metabolized to be active. Their clinical use is limited by the toxicity associated with some of their metabolites. Palifosfamide has shown efficacy in diverse cancer models. ZIOPHARM Oncology Inc, under license from Dekk-Tec Inc, was developing palifosfamide, a formulation of isophosphoramide mustard with tris(hydroxymethyl)aminomethane salt-stabilization (palifosfamide-tris) and previously with lysine-stabilization (palifosfamide-lys). Preclinical studies and phase I and I/II clinical trials demonstrated that palifosfamide-tris had an antitumor efficiency comparable or superior to that of ifosfamide. To date ZIO-201 is not present in ZIOPHARM pipeline.