1345675-02-6

ETP-46464 is used as an ATR inhibitor in the treatment of cancer-associated mutations.

etp-46464 is a potent and selective inhibitor for atr (ic50 = 25 nm).atr (atm- and rad3-related) is a member of pikk (phosphatidylinositol 3-kinase-like kinases) that regulates the dna damage response pathways. it is a dna damage sensor that is activated upon genotoxic stresses (e.g. ionizing radiation, uv radiation and dna replication stalling) and phosphorylates its downstream substrates (e.g. p53, brca1 and chek1).etp-46464 abolished the g2/m checkpoint. it caused the presence of micronuclei or completely fragmented nuclei in cells under ionizing radiation. cells treated simultaneously with hydroxyurea and etp-46464 exhibited elevated atm and chk2 phosphorylation. in u2os cells, etp-46464 promoted the breakage of stalked replication forks. [1]

mTOR

mTOR: 0.6 nM (IC₅₀); ATR: 14 nM (IC₅₀); ATM: 545 nM (IC₅₀); DNA-PK: 36 nM (IC₅₀); PI3Kα: 170 nM (IC₅₀)

1. toledo li, murga m, zur r et al. a cell-based screen identifies atr inhibitors with synthetic lethal properties for cancer-associated mutations. nat struct mol biol. 2011 jun;18(6):721-7.