ETP-46464 is an inhibitor of the DNA damage response kinase Ataxia-telangiectasia mutated (ATM)- and Rad3-related (ATR) with an IC50 value of 25 nM. It also inhibits mTOR and DNA-dependent protein kinase (IC50s = 0.6 and 36 nM, respectively), and is moderately active against PI3Kα and ATM (IC50s = 170 and 545 nM, respectively). Pharmacological inhibition of ATR is reported to generate replicative stress, leading to chromosomal breakage in the presence of conditions that stall replication forks. ETP-46464 has been shown to be toxic to p53-deficient cells, which is exacerbated by replicative stress-generating conditions such as the overexpression of cyclin E.
