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    InvivoChem Cat #: V0204
    CAS #: 1345675-02-6Purity ≥98%

    Description: ETP-46464 (ETP46464) is a novel, potent and selective inhibitor of ATR (Ataxia-telangiectasia mutated) and mTOR (mammalian target of rapamycin) with potential anticancer activity. It inhibits ATR/mTOR with IC50 of 25 nM and 0.6 nM, respectively. It also inhibits PI3Kα and ATM with IC50s of 170 and 545 nM, respectively. ATR is a DNA damage response kinase, and inhibition of ATR by ETP-46464 is reported to generate replicative stress, leading to chromosomal breakage of stalked replication forks. 

    References: Nat Struct Mol Biol. 2011 Jun;18(6):721-7. 

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    Molecular Weight (MW)




    CAS No.



    -20℃ for 3 years in powder form

    -80℃ for 2 years in solvent

    Solubility (In vitro)

    DMSO: 6 mg/mL (12.8 mM)

    Water: <1 mg/mL

    Ethanol: <1 mg/mL

    Other info

    Chemical Name: α,α-dimethyl-4-[2-oxo-9-(3-quinolinyl)-2H-[1,3]oxazino[5,4-c]quinolin-1(4H)-yl]-benzeneacetonitrile


    InChi Code: InChI=1S/C30H22N4O2/c1-30(2,18-31)23-8-10-24(11-9-23)34-28-22(17-36-29(34)35)16-33-27-12-7-19(14-25(27)28)21-13-20-5-3-4-6-26(20)32-15-21/h3-16H,17H2,1-2H3

    SMILES Code: N#CC(C)(C)C1=CC=C(N(C2=C3C=NC4=CC=C(C5=CC6=CC=CC=C6N=C5)C=C24)C(OC3)=O)C=C1


    ETP46464; ETP 46464; ETP-46464; ATM Inhibitor III; ATR Inhibitor III

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    In Vitro

    Kinase Assay: Compounds (e.g., ETP-46464) and control inhibitors are delivered directly to cell media (100 μL per well) with a multi-well pipette at a final concentration of 10 μM. Media content is homogenized by carefully vortexing plates at 500 rpm. Prior to 4-hydroxy-tamoxifen (4-OHT) addition, Compounds (e.g., ETP-46464 ) are incubated at 37ºC for 15 minutes. Next, to induce ATR activity, 4-OHT is added to all wells and incubated for 60 minutes at 37ºC. Finally, cells are fixed with paraformaldehyde and processed for IF. Every compound (e.g., ETP-46464) is analyzed at least in three independent experiments.


    Cell Assay: ETP-46464 shows almost full activity against ATR at 100 nM. ETP-46464 inhibits the activity of PI3Kα, mTOR and DNA-PKcs with IC50s of 170, 0.6 and 36 nM. ETP-46464 is able to promote the breakage of stalled replication forks. Exposure to ETP-46464 leads the generation of substantial amounts of DNA damage in replicating cells. 1 μM ETP-46464 abrogates the ionizing radiation-induced G2/M checkpoint and leads to the presence of micronuclei or completely fragmented nuclei in cells. ETP-46464 is particularly toxic for p53-deficient cells, which is exacerbated by replicative stress-generating conditions such as the overexpression of cyclin E.

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    Toledo LI, 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.



    These protocols are for reference only. InvivoChem does not independently validate these methods.

    Effect of the compounds in the G2/M checkpoint. Nat Struct Mol Biol. 2011 Jun;18(6):721-7.


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