As a proof‐of‐concept, we have explored this strategy with the development of nitroaromatic hypoxia‐activated prodrugs of AZD6738, which are reduced by NADPH‐cytochrome P450 oxidoreductase (CYPOR) and subsequently metabolized by aminopeptidase CD13 to release AZD6738 in the hypoxic tumor microenvironment (Scheme 1). The gene discussed is ANPEP; the disease is neoplasm.