M4344 (VX-803, Gartisertib) is a highly potent, selective ATR inhibitor with Ki<0.15 nM.
M4344 (VX-803, Gartisertib) showed minimal inhibitory activity against unrelated kinases, with >100-fold selectivity for ATR over 308/312 kinases tested.
M4344 suppressed cancer cell proliferation at lower concentrations, similarly to BAY1895344 and was more potent than berzosertib (VX-970, M6620), ceralasertib, and VE-821.
M4344 (25 nM) strongly suppressed cell viability of prostate DU145 cancer cells in combination of CPT at nanomolar concentrations, M4344 (10 nM) blocked CPT-induced activation of CHK1, a main downstream effector of ATR.
M4344 kills cancer cells under replication stress (RepStress) and with NE genomic signatures by replication-mediated DNA damage.
M4344 synergizes with clinical TOP1 inhibitor (Exatecan), as well as a broad range of widely used clinical agents including etoposide, gemcitabine, cisplatin, and talazoparib.
M4344 is active in patient-derived tumor organoids and xenograft models.