A cell-permeable aminopyrazinyl-sulfone compound that acts as a potent, reversible and ATP-competitive inhibitor of ATR kinase (IC50 = 12nM; Ki = 6nM) with excellent selectivity over ATM, DNA-PK (IC50 > 8uM) and in a 50-kinase panel (% inhibition at 2uM = 59, 57, 55, 52, 43 and 42 for AMPK, Lck, RIPK2, Ret, IKK-alpha and FGFR3, respectively). Shown to block pH2AX-Ser139 (IC50 = 420nM in hydroxyurea treated HT29 cells) and preferentially enhance cisplatin cytotoxicity against tumor cells over normal cells by ~7-fold at 620nM.
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