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A harmless molecule that turns into a poison only where there is no oxygen, which in the body means inside a tumour.
Tumour cores are hypoxic in a way normal tissue is not, so a prodrug reduced only under low oxygen should be tumour-selective. Evofosfamide failed two phase 3 trials in 2015; the field has since focused on better patient selection using hypoxia imaging or gene signatures, and on newer scaffolds. It remains a clean idea with a poor clinical record.
One-electron reduction of a nitroaromatic or quinone trigger is reversed by oxygen; where oxygen is absent, fragmentation releases an active cytotoxin.
Query for this technology: (TITLE:"Hypoxia-activated prodrugs" OR ABSTRACT:"Hypoxia-activated prodrugs") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Hypoxia-activated prodrugs, not a curated reading list.
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