DNA repair and redox activities and inhibitors of apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1): a comparative analysis and their scope and limitations toward anticancer drug development.

Abstract

The apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional enzyme involved in DNA repair and activation of transcription factors through its redox function. The evolutionarily conserved C- and N-termini are involved in these functions independently. It is also reported that the activity of APE1/Ref-1 abruptly increases several-fold in various human cancers. The control over the outcomes of these two functions is emerging as a new strategy to combine enhanced DNA damage and chemotherapy in order to tackle the major hurdle of increased cancer cell growth and proliferation. Studies have targeted these two domains individually for the design and development of inhibitors for APE1/Ref-1. Here, we have made, for the first time, an attempt at a comparative analysis of APE1/Ref-1 inhibitors that target both DNA repair and redox activities simultaneously. We further discuss their scope and limitations with respect to the development of potential anticancer agents.