YU238259

Description	YU238259 exhibits potent synthetic lethality in the setting of DNA damage response and DNA repair defects. Treatment with YU238259 is not only synergistic with ionizing radiation (IR), etoposide, and PARP inhibition, but this synergism is heightened by BRCA2-deficiency. Synthetic lethality of YU238259 in HDR-deficient cells results from accumulation of unresolved DSBs following additional inhibition of residual HDR pathway activity. Inhibition of HDR activity by YU238259 has little to no effect on the NHEJ pathway. YU238259 sensitizes tumor cells to radiation therapy and DSB-inducing chemotherapy.Growth of BRCA2-deficient human tumor xenografts in nude mice is significantly delayed by YU238259 treatment even in the absence of concomitant DNA-damaging therapy.
Pathways	Cell Cycle/DNA Damage PI3K/Akt/mTOR
Targets	DNA PK

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