ATM/ATR are members of the PI3 family of serine-threonine kinases and function as essential links between the sensors and effectors of the DNA damage response. The roles of ATM and ATR partially overlap and are cooperative; however they are also known to play distinct roles in protecting the cell from DNA damage. ATM is mostly responsible for sending signals from DSBs (double-strand breaks) induced by ionizing radiation while the closely related ATR responds to UV damage or stalled replication forks. ATM and ATR are known to phosphorylate common as well as specific substrates to activate checkpoint signaling. The G1, S, and G2 cell cycle checkpoints are primarily regulated by the ATM (ataxia telangiectasia, mutated) and ATR (ATM and Rad3-related) protein kinases.
||CP-466722 is a rapidly reversible inhibitor of ATM, with an IC50 of 4.1 μM, and has no effects on PI3K or closely related PI3K-like protein kinase (PIKK) family members.
||KU-55933 is a potent ATM inhibitor with an IC50 and Ki of 12.9 and 2.2 nM, respectively, and highly selective for ATM as compared to DNA-PK, PI3K/PI4K, ATR and mTOR.
||VE-821 is a potent ATP-competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM.
||VE-822 is an ATR inhibitor with Ki value of <0.2 nM, also inhibits ATM with Ki of 34 nM.
||KU-60019 is an improved analogue of KU-55933, with IC50 of 6.3 nM for ATM in cell-free assays, 270- and 1600-fold more selective for ATM than DNA-PK and ATR,and is a highly effective radiosensitizer.
||ETP-46464 is an effective mTOR and ATR inhibitor with IC50s of 0.6 and 14 nM, respectively.
||BAY-1895344 hydrochloride is a potent, orally available and selective ATR inhibitor, with IC50 of 7 nM.
||AZD6738 is a potent inhibitor of ATR kinase with an IC50 of 1 nM.
||BAY 1895344 is a potent, highly selective and orally available ATR inhibitor with an IC50 of 7 nM.
||GSK 635416A is a novel ATM inhibitor with highly selective radiosensitizing activity, inhibits radiation induced phosphorylation of ATM.
||A potent G2 checkpoint inhibitor that specifically abrogates the DNA double-stranded break (DSB)-induced G2 checkpoint.
||AZ32 (ATM inhibitor AZ32) is a potent, selective, orally bioavailable, BBB-penetrating ATM inhibitor with IC50 of <6.2 nM, effectively blocks ATM auto-phosphorylation at S1981 with IC50 of 0.31 uM.