Glufosfamide (DB06177): A Comprehensive Report on a Targeted Alkylating Agent

Executive Summary

[Glufosfamide (DrugBank ID: DB06177) is an investigational, third-generation oxazaphosphorine derivative designed as a targeted chemotherapeutic agent. Structurally, it is a conjugate of the active cytotoxic metabolite of ifosfamide—isophosphoramide mustard (IPM)—and a $\beta$-D-glucose molecule. This design is predicated on the hypothesis of metabolic targeting, aiming to exploit the increased glucose uptake characteristic of many malignant tumors to achieve preferential drug delivery and enhanced efficacy. The mechanism of action involves cellular uptake via glucose transporters, followed by intracellular cleavage to release the active IPM, which then functions as a DNA alkylating agent, inducing cell cycle arrest and apoptosis. A key theoretical advantage of this design is the circumvention of hepatic cytochrome P450 activation required by its parent compound, ifosfamide, thereby avoiding the production of toxic metabolites such as acrolein.]