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KU0060648
NHEJ pathway inhibitor; Inhibits DNA-dependent protein kinase (DNA-PK)
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KU0060648 is an ATP-competitive and highly potent inhibitor of DNA-dependent protein kinase (DNA-PK), with IC₅₀ values of 19 nM in MCF7 human breast cancer cells and 170 nM in SW620 human colon cancer cells. KU0060648 also inhibits phosphoinositide 3-kinase (PI3K) with IC₅₀ values of 39 nM in MCF7 cells and > 10 µM in SW620 cells, which suggests a cell-dependent mechanism (Munck et al.).
GENOME EDITING
- Reduces the frequency of non-homologous end joining (NHEJ) and increases the efficiency of homology-directed repair (HDR) in CRISPR-Cas9 genome editing (Robert et al.).
CANCER RESEARCH
- Inhibits tumor growth and sensitizes human cancer cells to DNA double-strand-break (DSB)-inducing therapies (chemo- or radio-therapy) by inhibiting both DNA-PK and PI3K and preventing the execution of DSB repair (Chen et al.; Dietlein et al.; Munck et al.).