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CNOB (6-chloro-9-nitro-5-oxo-5H-benzo[a]phenoxazine) is a novel, fluorescent, reductive prodrug developed by researchers at Stanford University for the treatment of cancer, including HER2-positive breast cancer. It is designed for use in gene-directed enzyme prodrug therapy (GDEPT) or exosome-directed enzyme prodrug therapy (EXO-DEPT). CNOB is selectively activated by the bacterial nitroreductase enzyme ChrR6 (or its humanized version HChrR6) to generate the highly cytotoxic and fluorescent compound 9-amino-6-chloro-5H-benzo[a]phenoxazine-5-one (MCHB). MCHB acts as a DNA intercalator, localizes to the mitochondria, disrupts mitochondrial membrane potential, and induces apoptosis in cancer cells. The fluorescent properties of both CNOB and MCHB allow for non-invasive real-time imaging and pharmacokinetic monitoring in vivo.
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