Description:
ETP-46464 is a cell-permeable quinoline-containing heterotricyclic compound that acts as a potent inhibitor against mTOR, ATR, DNA-PK, PI 3-Kα, and ATM (IC50 = 0.6, 14, 36, 170, and 545 nM, respectively) and preferentially suppresses radiation-induced cellular ATR activity (>90% at 500 nM) over ATM or DNA-PK activity (IC50 > 5 uM) in U2OS cells, while exhibiting much reduced or little potency toward a panel of 26 other kinases (>55% inhibition at 5 uM). ETP-46464 is Shown to synergize with UCN-01 in replicative stress induction in S-phase replicating U2OS (1.5-, 61-, and 190-fold of control RS, respectively, with 1 uM ETP-46464, 50 nM UCN-01, or combined treatment).