Compound 401 is a cell-permeable pyrimido-isoquinolinone compound that acts as a potent, reversible, and ATP-competitive inhibitor of DNA-PK (IC50 = 280 nM) with ~19-fold selectivity over mTOR (FRAP) (IC50 = 5.3 μM). Compound 401 exhibits much reduced or no activity against 43 other commonly studied kinases, including PI 3-K, ATM, and ATR. Compound 401 has been shown to induce apoptosis and inhibit FRAP-dependent growth in TSC1-/- murine embryo fibroblasts.
