Molecular Weight (MW)

470.52

Formula

C30H22N4O2

CAS No.

1345675-02-6

Storage

-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 Key: DPLMXAYKJZOTKO-UHFFFAOYSA-N

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

Synonyms

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.

In Vivo

Animal model

Formulation & Dosage

References

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.