isophosphoramide mustard

Isophosphoramide mustard is a small-molecule bifunctional alkylating agent and the principal cytotoxic metabolite of ifosfamide; it forms DNA interstrand cross-links (notably via N7-guanine) yielding irreparable 7-atom cross-links that inhibit DNA replication and transcription, leading to tumor cell death. Preclinical studies showed antitumor activity comparable to cyclophosphamide and ifosfamide across multiple murine tumor models, including activity in cyclophosphamide-resistant leukemia, though with lower activity in intracerebral P388 and B16 melanoma models. As the active moiety of ifosfamide, development efforts included stabilized salt forms such as a lysine salt (ZIO-201) to improve solution stability and enable IV and oral administration, with early clinical development in advanced cancers and sarcoma. Unlike ifosfamide, IPM itself is not metabolized to acrolein or chloroacetaldehyde, suggesting a lower risk of bladder and CNS toxicity when delivered directly as stabilized formulations.

Other names

isophosphoramide mustard lysineIPM-lysinepalifosfamide