Sigma-Aldrich Atr Inhibitor IV - Cas 123

Assay

≥98% (HPLC)

Quality Level

100

Form

solid

Potency

13 nM K_i

Manufacturer/Tradename

Calbiochem^®

Storage Condition

OK to freeze
protect from light

Color

yellow

Solubility

DMSO: 100 mg/mL

Storage Temp.

2-8°C

Inchi

1S/C18H16N4O3S/c1-26(24,25)14-9-7-12(8-10-14)15-11-20-17(19)16(22-15)18(23)21-13-5-3-2-4-6-13/h2-11H,1H3,(H2,19,20)(H,21,23)

General Description

A cell-permeable phenylpyrazine derivative that acts as a potent, ATP-competitive (K _i= 13 nM; IC₅₀/[ATP] = 70 nM/50 µM and 128 nM/100 µM), ATR-selective inhibitor with much reduced or little potency against 4 related PIKKs (K _i= 2.2, 3.9, 16, and >1 µM, respectively, against DNA-PK, PI 3-Kγ, ATM, and mTOR) and 50 other kinases. Shown to selectively inhibit ATR-dependent H2AX Ser139 & Chk1 Ser345 phosphorylation (complete inhibition at 10 µM in HT29 and HFL1 cultures) without affecting ATM- and DNA-PK-mediated H2AX or ATM-mediated Chk2 phosphorylation. Short-term (24 H) VE-821 treatment, either alone or in synergy with Cisplatin (Cat. No. 232120), results in reversible cytostatic growth arrest regardless of cellular ATM-p53 pathway activity, while cytotoxicity and Cisplatin synergism in cell death induction is reported to occur only upon long-term VE-821 exposure (≥72 H) in cultures with ATM-p53 pathway defects.A cell-permeable phenylpyrazine derivative that acts as a potent, ATP-competitive (K _i= 13 nM; IC₅₀/[ATP] = 70 nM/50 µM and 128 nM/100 µM), ATR-selective inhibitor with much reduced or little potency against 4 related PIKKs (K _i= 2.2, 3.9, 16, and >1 µM, respectively, against DNA-PK, PI 3-Kγ, ATM, and mTOR) and 50 other kinases. Shown to selectively inhibit ATR-dependent H2AX Ser139 & Chk1 Ser345 phosphorylation (complete inhibition at 10 µM in HT29 and HFL1 cultures) without affecting ATM- and DNA-PK-mediated H2AX or ATM-mediated Chk2 phosphorylation. Short-term (24 H) VE-821 treatment, either alone or in synergy with Cisplatin (Cat. No. 232120), results in reversible cytostatic growth arrest regardless of cellular ATM-p53 pathway activity, while cytotoxicity and Cisplatin synergism in cell death induction is reported to occur only upon long-term VE-821 exposure (≥72 H) in cultures with ATM-p53 pathway defects.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Biochem/Physiol Actions

Cell permeable: yesReversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Other Notes

Prevo, R., et Al. 2012,Cancer Biol. Ther. 13,1072; Pires, I.M., et Al. 2012,Br. J. Cancer 107,291; Reaper, P.M., et Al. 2011,Nat. Chem. Biol. 7,428.CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany