Berzosertib (M6620, VX-970, VE-822) is a highly potent, selective ATR inhibitor with Ki of 0.17 nM, pH2AX IC50 of 19 nM.
M6620 (Berzosertib, VX-970) displays >250-fold selectivity over ATM, and no inhibition against DNA-PK, 278 out of 291 kinases showed <50% inhibition at 400 nM, only Flt4 kinase shows less than 100-fold selectivity.
M6620 (Berzosertib, VX-970) preferentially inhibited ATR-Chk1-CDC25a signaling, abrogated the radiotherapy-induced G2-M checkpoint, delayed resolution of DNA double-strand breaks, and reduced colony formation after radiotherapy in TNBC cells relative to normal-like breast epithelial cells.
M6620 (Berzosertib, VX-970) demonstrated durable regressions in small cell lung cancers with high replication stress when combined with TOP1 inhibitor topotecan.
