APX3330 has been extensively characterized as a direct, highly selective inhibitor of Ref-1/APE1 redox activity that does not affect the protein’s endonuclease activity in tumors (Section IV; Fig. 6).13, 17, 21, 22, 27–29 Treatment with APX3330 slows tumor growth and progression, with limited toxicity, in both in vitro and in vivo models.13, 18, 30, 31 APX3330 is entering clinical trials in mid-2017 and is discussed in Section V of this review. Here, APEX1 is linked to neoplasm.