VX-984

VX-984 is an orally available small molecule that acts as a selective ATP-competitive inhibitor of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). By inhibiting DNA-PKcs, VX-984 disrupts the non-homologous end joining (NHEJ) pathway responsible for repairing DNA double-strand breaks (DSBs), particularly those induced by ionizing radiation or chemotherapeutic agents. This inhibition prevents efficient repair of DSBs in tumor cells, thereby enhancing their sensitivity to chemo- and radiotherapy and promoting increased tumor cell death. Preclinical studies have shown that VX-984 preferentially impairs DSB repair in malignant cells compared to normal cells and can cross the blood-brain barrier. It has been investigated primarily for use in glioblastoma (GBM), non-small cell lung cancer (NSCLC), and other advanced solid tumors[1][2][3][6][7].

Other names

DNA-dependent protein kinase inhibitor VX-984