We have developed a new class of DNA-PKi with excellent activity as radiosensitisers in preclinical models. The lead compound, DDRx-124, is a low nM inhibitor of DNA-PK, and is a DNA-PK-dependent radiosensitiser.

Additionally, we have developed hypoxia-activated prodrugs that release DNA-PKi under hypoxia, exemplified by lead compound DDRx-125, to provide selective tumour targeting. This approach can selectively radiosensitise radioresistant (hypoxic) cells in tumours.