AZD6738 is a potent inhibitor of ATR kinase activity with an IC50 of 1 nM against the isolated enzyme and 74 nM against ATR kinase-dependent CHK1 phosphorylation in cells.

IC50 value: 1 nM

Target: ATR kinase

in vitro: AZD6738 is an orally active and bioavailable ATR kinase inhibitor. AZD6738 induces cell death and senescence in non-small cell lung cancer (NSCLC) cell lines. AZD6738 potentiates the cytotoxicity of cisplatin and gemcitabine in NSCLC cell lines with intact ATM kinase signaling, and potently synergizes with cisplatin in ATM-deficient NSCLC cells. AZD6738 inhibits ATR kinase activity and impairs viability of NSCLC. [1]

in vivo: In contrast to expectations, daily administration of AZD6738 and ATR kinase inhibition for 14 consecutive days is tolerated in mice and enhances the therapeutic efficacy of cisplatin in xenograft models. Remarkably, the combination of cisplatin and AZD6738 resolves ATM-deficient lung cancer xenografts. [1]