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  • An orally available inhibitor of DNA-dependent protein kinase (DNA-PK), with potential antineoplastic and chemo/radiosensitizing activities. Upon oral administration, the DNA-PK inhibitor MSC2490484A binds to and inhibits the activity of DNA-PK. This inhibits the ability of tumor cells to repair damaged DNA, which may lead to a reduction in cellular proliferation of cancer cells expressing DNA-PK. DNA-PK, a serine/threonine kinase and a member of the PI3K-related kinase subfamily of protein kinases, is activated upon DNA damage and plays a key role in repairing DNA double-strand breaks (DSBs) via the DNA nonhomologous end joining (NHEJ) pathway. The enhanced ability of tumor cells to repair DSBs plays a major role in the resistance of tumor cells to chemo- and radiotherapy. Check for \'https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C120036\' active clinical trials using this agent. (\'http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C120036\' NCI Thesaurus)
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