CYP1A1 and neoplasm: Besides hypoxia, the activation of AQ4N also depends on cytochrome P450 (CYP450) activating reductases, which are also dominantly responsible for the activation of most other HAPs.13 Two main CYP450 enzymes, CYP1A1 and 2B6, are shown to metabolize AQ4N into AQ4 (a potent inhibitor of topoisomerase II) efficiently (Figure S1, Supporting Information).14 However, O2 blocks this activation process by outcompeting AQ4N for heme‐centered active site of CYP450, conferring the selectivity of AQ4N in eradicating hypoxic tumor cells.15