BCCA7693

BCCA7693 is a novel, orally bioavailable small molecule inhibitor of DNA-dependent protein kinase (DNA-PK), a key enzyme in the non-homologous end joining (NHEJ) pathway for DNA double-strand break repair. Developed by researchers at BC Cancer, BCCA7693 was identified through a structure-based drug development program and selected for its high potency, selectivity, and favorable ADME characteristics. Preclinical studies demonstrate that BCCA7693 significantly sensitizes tumors to radiotherapy and various targeted therapies, including MEK, KRAS, and PARP inhibitors. By inhibiting the repair of chromothripsis-induced DNA damage, it effectively blocks the development of acquired resistance in models of KRAS, BRAF, and BRCA-mutated cancers, such as Colo-205 xenografts. Its safety profile in animal models suggests a wide therapeutic window for combination regimens without the increased toxicity often associated with conventional DNA-damaging agents.