5.04972

ATR Inhibitor IV

• Synonym(s): ATR Inhibitor IV, VE821, 3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide, VE-821, ATM and Rad3-Related Inhibitor IV
• Empirical Formula (Hill Notation): C₁₈H₁₆N₄O₃S
• CAS Number: 1232410-49-9
• Molecular Weight: 368.41
• MDL number: MFCD19443686

Properties

• 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)
• InChI key: DUIHHZKTCSNTGM-UHFFFAOYSA-N

Description

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: yes

Reversible: 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. Cancer107, 291; Reaper, P.M., et al. 2011, Nat. Chem. Biol.7, 428.

Legal Information

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

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable