NCIt synonyms : DNA-dependent Protein Kinase Inhibitor AZD7648; 7-Methyl-2-[(7-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino]-9-(tetrahydro-2H-pyran-4-yl)-7,9-dihydro-8H-purin-8-one;
NCIt related terms : AZD-7648;
NCIt definition : An orally bioavailable ATP-competitive inhibitor of DNA-dependent protein kinase (DNA-PK),
with potential chemo/radiosensitizing and antineoplastic activites. Upon oral administration,
DNA-PK inhibitor AZD7648 selectively targets, binds to and inhibits the activity of
DNA-PK, thereby interfering with the non-homologous end joining (NHEJ) process and
preventing repair of DNA double strand breaks (DSBs) caused by ionizing radiation
or chemotherapeutic treatment. This increases chemo- and radiotherapy cytotoxicity
leading to enhanced tumor cell death. AZD7648 may also increase the effect of poly(ADP-ribose)
polymerase (PARP) inhibitors and may work as a monotherapy in tumors with high endogenous
levels of DNA damage resulting from defects in other DNA repair pathways. The enhanced
ability of tumor cells to repair DSBs plays a major role in the resistance of tumor
cells to chemo- and radiotherapy. DNA-PK plays a key role in the NHEJ pathway and
DSB repair.;
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