Ku inhibitor

The Ku inhibitor (specifically the series including NERx-329) is a first-in-class small-molecule inhibitor of the DNA-dependent protein kinase (DNA-PK) pathway. Developed by NerX Biosciences, it utilizes a novel, ATP-independent mechanism that targets the Ku70/80 heterodimer interface. By blocking the binding of Ku70/80 to DNA double-strand breaks—the initial and essential step in DNA-PK activation—the drug effectively prevents the assembly of the non-homologous end joining (NHEJ) complex. This approach offers enhanced selectivity and reduced toxicity compared to traditional DNA-PKcs inhibitors. Preclinical studies demonstrate that these inhibitors potently sensitize cancer cells, particularly in non-small cell lung cancer (NSCLC), to ionizing radiation, etoposide, bleomycin, and topoisomerase I inhibitor-based antibody-drug conjugates (ADCs) like DXd.

Other names

Ku70/80 inhibitorKu-targeted DNA-PK inhibitor