AZD7648 (C09-0736-032)

InformationAZD7648 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.TargetsDNA-PK (Cell-free assay) 0.6 nMIn vitroAZD7648 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 vivoAZD7648 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. Specification: 10mM in DMSO Molecular Formula: C18H20N8O2 Molecular Weight: 380.4 PubChem CID: 135151360 Isomeric SMILES: CC1=CC2=NC=NN2C=C1NC3=NC=C4C(=N3)N(C(=O)N4C)C5CCOCC5