The objective of the proposed research is to synthesize new analogs of isophosphoramide mustard (IPM), the ultimate alkylating metabolite of the clinical antitumor agent, ifosfamide, for comparison of their antitumor activity in vivo vs. experimental tumors in mice and human tumor xenografts in athymic mice. The in vivo activity of the new analogs will be compared with the prototype (IPM), as well as with ifosfamide and cyclophosphamide, in order to identify a possible clinical candidate. Tumor models for in vivo evaluation will consist of M5076 mouse sarcoma and 16/C mouse mammary tumor and of MCF-7 human mammary adenocarcinoma and U251 human CNS tumor. The overall goal is to identify a more antitumor-active IPM analog for possible preclinical development in a Phase II study.
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