DNA Alkylation via Bromo-Isophosphoramide Mustard Activation Under Hypoxia

This target refers to a therapeutic strategy that exploits the low-oxygen (hypoxic) environment commonly found in solid tumors. It involves the use of prodrugs, such as evofosfamide, that are selectively activated under hypoxic conditions to release bromo-isophosphoramide mustard (Br-IPM), a potent DNA alkylating agent. Upon activation, Br-IPM induces cytotoxic DNA crosslinks, leading to tumor cell death while minimizing systemic toxicity due to the prodrug's stability in normal oxygen conditions.

Other names

Hypoxia-activated bromo-isophosphoramide mustard DNA alkylationEvofosfamide mechanism of action

Bromo-isophosphoramide mustard forms intra- and interstrand DNA crosslinks, inhibiting replication and transcription leading to cell death. Activation is triggered by hypoxia.