881375-00-4

KU-0060648 is a dual inhibitor of DNA-PK and PI3Kα, PI3Kβ, PI3Kδ.

ChEBI: 2-(4-ethyl-1-piperazinyl)-N-[4-[2-(4-morpholinyl)-4-oxo-1-benzopyran-8-yl]-1-dibenzothiophenyl]acetamide is a member of dibenzothiophenes.

KU-0060648 is a very potent dual inhibitor of DNA-PK and PI3K. The IC50 values for inhibition of DNA-PK in MCF7 and SW620 cells are 19 and 170 nMrespectively. The compound KU-0060648 inhibits MCF7 PI3K activity with an IC50 of 39 nMbut is inactive against PI3K in SW620suggesting a cell-dependent mechanism of inhibition. KU-0060648 increases sensitivity to DNA damaging cytotoxic drugs such as etoposide and doxorubicin in tumor cell lines expressing DNA-PK. KU-0060648 stimulates Cas9 (CRISPR associated protein 9) mediated genome editing by enhancing the rate of homology directed-repair (HDR) and decreasing the rate of NHEJ (non-homologous end-joining).''KU-0060648 is observed to inhibit proliferation and initiate apoptosis in hepatocellular carcinoma. KU-0060648 is useful in chemotherapy as it increases the efficiency of double stranded breaks initiated by anticancer drugs.

PI3Kα: 4 nM (IC₅₀); PI3Kβ: 0.5 nM (IC₅₀); PI3Kγ: 0.594 μM (IC₅₀); PI3Kδ: 0.1 nM (IC₅₀); DNA-PK: 8.6 nM (IC₅₀)

Store at -20°C