API-93

API-93 is a novel small molecule inhibitor of apurinic/apyrimidinic deoxyribonuclease 1 (APEX1), identified through a high-throughput functional screen of approximately 100,000 compounds. APEX1 is an enzyme whose elevated activity in multiple myeloma (MM) contributes to dysregulated homologous recombination (HR) and genomic instability. API-93 works by inhibiting APEX1 activity, which leads to a reduction in DNA breaks, decreased HR activity, and induction of G2/M cell cycle arrest. While it shows minimal single-agent cytotoxicity, API-93 significantly enhances the efficacy of standard chemotherapeutic and immunomodulatory agents such as cyclophosphamide, melphalan, lenalidomide, and bortezomib in myeloma cell lines. Furthermore, it has been shown to decrease the acquisition of new genomic copy number changes, potentially slowing clonal evolution in cancer.