Schematic representation of PI3K-related signaling and associated inhibitors. (A) ATP-competitive dual PI3K/mTOR inhibitors such as BEZ235 antagonize PI3K and both mTOR complexes. Rapamycin analogs such as Everolimus cause allosteric hindrance of mTORC1 without direct inhibitory effects on other PI3K-related kinases. KU63794 is an ATP-competitive mTORC1/2 inhibitor; BKM120 is an ATP-competitive PI3K inhibitor. (B) Because of close structural homology between PI3K/mTOR and the PI3K-related DNA damage response kinases (ATM/ATR and DNA-PK), BEZ235 can antagonize the DNA damage response. KU57788 and KU55933 are selective ATP-competitive antagonists of DNA-PK and ATM, respectively. Phosphorylation of p53 (at Ser15) and γH2AX is the composite end point of the activity of ATM/ATR and DNA-PK.