AZD7648是DNA-PK的有效抑制剂，IC50为0.6 nM，其选择性比对所检测激酶库中其他的396种激酶高100倍以上。 AZD-7648 诱导细胞凋亡 (apoptosis)，具有抗肿瘤活性。 Information AZD7648 AZD7648 is a potent inhibitor of DNA-PK with an IC50 of 0.6 nM in biochemical assay and more than 100-fold selective against 396 other kinases. Targets DNA-PK (Cell-free assay) 0.6 nM In vitro AZD7648 inhibits IR-induced DNA-PK S2056 auto phosphoryalation with an IC50 = 92 nM in A549 non-small cell lung cancer (NSCLC) cells. In A549 cells, AZD7648 (≥1 µM) in combination with 2Gy IR for 48 hours leads to a significant accumulation of cells arrested in the G2/M of the cell cycle, a 4-fold increase in micronuclei formation, and 3-fold induction of γH2AX, pATM S1981 and 53BP1 foci formation compared with IR alone. In vivo AZD7648 is a potent and highly selective DNA-PK inhibitor, with good crystalline solubility, permeability and metabolic stability, good bioavailability and predictable pharmacokinetics in preclinical species, and potent knockdown of pRPA and regressions in murine xenograft models when combining with olaparib or radiation.