th 302

Evofosfamide (TH-302) is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard (Br-IPM) conjugated with 2-nitroimidazole, possessing potential antineoplastic activity. Under hypoxic conditions, typical of hypoxic tumors, the 2-nitroimidazole moiety is reduced, releasing the DNA-alkylating Br-IPM moiety, which induces intra- and inter-strand DNA crosslinks that inhibit DNA replication and cell division, potentially causing apoptosis in tumor cells. The inactive form of the prodrug remains stable under normoxic conditions, which may reduce systemic toxicity.