A cell-permeable phenylpyrazine derivative that acts as a potent, ATP-competitive (Ki= 13nM; IC50/[ATP] = 70nM/50uM and 128nM/100uM), ATR-selective inhibitor with much reduced or little potency against 4 related PIKKs (Ki= 2.2, 3.9, 16, and >1uM, respectively, against DNA-PK, PI 3-K-gamma, ATM, and mTOR) and 50 other kinases. Shown to selectively inhibit ATR-dependent H2AX Ser139 & Chk1 Ser345 phosphorylation (complete inhibition at 10uM in HT29 and HFL1 cultures) without affecting ATM- and DNA-PK-mediated H2AX or ATM-mediated Chk2 phosphorylation. Short-term (24h) VE-821 treatment, either alone or in synergy with Cisplatin, 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 (≥72h) in cultures with ATM-p53 pathway defects.
Synonyms:VE821, 3-amino-6-(4-(methylsulfonyl)phenyl)-N-phenylpyrazine-2-carboxamide, VE-821, ATM and Rad3-Related Inhibitor IV
Molecular Formula:C₁₈H₁₆N₄O₃S
Solubility:As reported
Primary Target:ATR
Primary Target Ki:13nM
Molar Mass:368.41
Appearance:Yellow solid
Purity:≥98% (HPLC)
Storage and Stability:May be stored at 4°C. For long-term storage store at -20°C. Stable for 6 months after receipt. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Store under inert gas. Light sensitive.
