AZD7648 (AZD-7648) is a potent, selective inhibitor of DNA-PK catalytic subunit (DNA-PKcs) with IC50 of 0.6 nM.
AZD7648 displays no significant off-target activity in the protein kinome and only weak activity versus PI3Kα/γ lipid kinases.
AZD7648 increases genomic instability, resulting in cell growth inhibition and apoptosis in combination with the PARP inhibitor olaparib.
AZD7648 enhanced olaparib efficacy across a range of doses and schedules in xenograft and PDX models.
AZD7648 sensitizes tumor cells to radiotherapy and induces type I IFN-dependent durable tumor control in MC38, CT26, and B16-F10 models
