YU238259 is a novel DNA double-strand break repair inhibitor exhibiting potent synthetic lethality in the setting of DNA damage response and DNA repair defects. YU238259 specifically inhibits homology-dependent DNA repair, but not non-homologous end-joining, in cell-based GFP reporter assays at concentration of 5μM. Treatment with YU238259 was not only synergistic with ionizing radiation, etoposide, and PARP inhibition, but this synergism was heightened by BRCA2 deficiency. Also it significantly delayed growth of BRCA2-deficient human tumor xenografts in nude mice through administration at dose of 3mg/kg, i.p., 3 days per week for 12 doses, even in the absence of concomitant DNA-damaging therapy.
YU238259 细胞实验
Cell Line
Concentration
Treated Time
Description
References
PEA2
10 µM
60 min
Enhance the cytotoxic effect of CDDP/VP-16 combination treatment
To validate the effect of YU238259 as an HDR inhibitor, results showed that the increased HDR efficiency in SHROOM1-deleted HEK293T cells was counteracted by YU238259.
Int J Mol Sci. 2020 Aug 13;21(16):5821.
YU238259 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
BRCA2-deficient tumor xenograft model
Intraperitoneal injection
3 mg/kg
3 times per week for a total of 12 doses
YU238259 significantly delayed the growth of BRCA2-deficient tumors.
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