Ceralasertib

Ceralasertib (AZD6738) is an orally active and bioavailable inhibitor of ATR kinase with an IC₅₀ of 1 nM. IC50 & Target: IC50: 1 nM (ATR kinase)^[1] In Vitro: Ceralasertib (AZD6738) is a potent inhibitor of ATR kinase activity with an IC₅₀ of 0.001 μM against the isolated enzyme and 0.074 μM against ATR kinase-dependent CHK1 phosphorylation in cells. Ceralasertib (AZD6738) induces cell death and senescence in non-small cell lung cancer (NSCLC) cell lines. Ceralasertib (AZD6738) impairs viability of four Kras mutant cell lines: H23, H460, A549, and H358. , with the lowest GI₅₀ and greatest maximal inhibition in H460 and H23 cells (1.05 μM, 88.0% and 2.38 μM, 86.2%, respectively). Ceralasertib (AZD6738) potentiates the cytotoxicity of CDDP and NSC 613327 in NSCLC cell lines with intact ATM kinase signaling, and potently synergizes with CDDP in ATM-deficient NSCLC cells^[1]. Ceralasertib (AZD6738) inhibits human breast cancer cell lines with IC₅₀ values less than 1 μM using MTT assay. Ceralasertib (AZD6738) induces cell cycle arrest and apoptosis. It downregulates DNA damage response molecules and cell proliferative signaling molecules^[2]. In Vivo: Daily administration of Ceralasertib (AZD6738) and ATR kinase inhibition for 14 consecutive days is tolerated in mice and enhances the therapeutic efficacy of CDDP in xenograft models. Remarkably, the combination of CDDP and Ceralasertib (AZD6738) resolves ATM-deficient lung cancer xenografts^[1].