5.00508

ATR Inhibitor III, ETP-46464

• Synonym(s): ATR Inhibitor III, ETP-46464, ATM Inhibitor III, mTOR Inhibitor XIII, PI 3-K Inhibitor XIX, ETP46464, 2-methyl-2-(4-(2-oxo-9-(quinolin-3-yl)-2H-[1,3]oxazino[5,4-c]quinolin-1(4H)-yl)phenyl)propanenitrile, ATM and Rad3-Related Inhibitor III, Ataxia-Telangiectasia Mutated Inhibitor III,
• Empirical Formula (Hill Notation): C₃₀H₂₂N₄O₂
• CAS Number: 1345675-02-6
• Molecular Weight: 470.52

Properties

• Assay: ≥99% (HPLC)
• Quality Level: 100
• form: powder
• potency: 14 nM IC₅₀
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: white
• solubility: DMSO: 10 mg/mL
• storage temp.: 2-8°C
• 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
• InChI key: DPLMXAYKJZOTKO-UHFFFAOYSA-N

Description

General description

A cell-permeable quinoline-containing heterotricyclic compound that acts as a potent inhibitor against mTOR, ATR, DNA-PK, PI 3-Kα, and ATM (IC₅₀ = 0.6, 14, 36, 170, and 545 nM, respectively) and preferentially suppresses radiation-induced cellular ATR activity (>90% at 500 nM) over ATM or DNA-PK activity (IC₅₀ >5 M) in U2OS cells, while exhibiting much reduced or little potency toward a panel of 26 other kinases (>55% inhibition at 5 M). Shown to synergize with UCN-01 (Cat. No. 539644) in replicative stress induction in S-phase replicating U2OS (1.5-, 61-, and 190-fold of control RS, respectively, with 1 M ETP-46464, 50 nM UCN-01, or combined treatment).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

A cell-permeable quinoline-containing heterotricyclic compound that acts as a potent inhibitor against mTOR, ATR, DNA-PK, PI 3-Kα, and ATM activity (IC₅₀ = 0.6, 14, 36, 170, and 545 nM, respectively, in cell-free kinase assays) and preferentially suppresses ionization radiation/IR-induced cellular ATR activity (>90% inhibition of IR-induced Chk1 pSer345 at 500 nM) over ATM or DNA-PK activity (IC₅₀ >5 µM against IR-induced ATM pSer189, Chk2 pThr68, DNA-PKcs pSer2056, and γH2AX) in U2OS cells, while exhibiting much reduced or little potency toward a panel of 26 other kinases (>55% inhibition at 5 µM). Shown to synergize with UCN-01 (Cat. No. 539644) in replicative stress/RS induction in S-phase replicating U2OS (% population with pan-nuclear γH2AX staining = 6.0% and 0.2%, respectively, with or without 8 h 5 µM ETP-46464 treatment; 1.5-, 61-, and 190-fold of control RS, respectively, with 1 µM ETP-46464 alone, 50 nM UCN-01 alone, or combined treatment). Likewise, ETP-46464 is also demonstrated to further enhance oncogenic mutations-caused RS elevation in MEF cultures (% RS population without/with 5 µM ETP-46464 treatment = 0.3/0.6, 1.3/2.5, 0.9/3.0, 3.9/11.4, respectively, in wt, p53^-/-, Cyclin E-transfected wt, and Cyclin E-transfected p53^-/- MEF).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
ATR

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Thanasoula, M., et al. 2012. EMBO J.31, 3398.
Toledo, L.I., et al. 2011. Nat Struct Mol Biol.18, 721.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 2
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable