AR03

AR03 is a novel small molecule inhibitor specifically targeting the endonuclease activity of the apurinic/apyrimidinic endonuclease 1 (APE1) enzyme. APE1 is a critical component of the base excision repair (BER) pathway, which repairs DNA damage caused by endogenous and exogenous agents, including chemotherapeutic drugs. AR03 selectively inhibits the DNA repair function of APE1 without affecting its redox signaling role. By blocking the repair of AP sites, AR03 leads to the accumulation of DNA strand breaks, resulting in enhanced cytotoxicity, cell cycle arrest, and apoptosis in cancer cells. Preclinical studies have demonstrated its efficacy in glioblastoma models, particularly when used in combination with alkylating agents like temozolomide (TMZ) and methyl methane sulfonate (MMS).