VE-821

SKU: orb1304605

Description

VE-821 is a potent and selective ATP-competitive inhibitor of the ATR kinase, with a Ki of 13 nM and an IC50 of 26 nM in biochemical assays. It is widely used in preclinical research to study DNA damage response pathways, demonstrating chemosensitizing effects in various cancer cell lines and in vivo tumor models.

Research Area

Molecular Biology, Signal Transduction

Key Properties

• CAS Number: 1232410-49-9
• MW: 368.4
• Purity: >98%
• Formula: C₁₈H₁₆N₄O₃S
• SMILES: CS(=O)(=O)c1ccc(cc1)-c1cnc(N)c(n1)C(=O)Nc1ccccc1
• Target: Kinase
• Solubility: Soluble in DMSO (40 mg/ml)

Bioactivity

• Target IC50:
  PI3Kγ:3.9 μM (Ki)|ATR:13 nM (Ki, cell free)|DNA-PK:2.2 μM (Ki)|ATM:16 μM (Ki)
• In Vitro:
  VE-821 exhibits high selectivity for ATR with minimal cross-reactivity against related PIKKs, including ATM, DNA-dependent protein kinase (DNA-PK), mammalian target of rapamycin, and phosphoinositol 3-kinase-γ (Kis of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively). It inhibits H2AX phosphorylation in hydroxyurea-treated HT29 cancer cells without affecting M059J or HT144 lines treated with neocarzinostatin . VE-821 significantly increases the sensitivity of PSN-1, MiaPaCa-2, and primary PancM pancreatic cancer cells to radiation and gemcitabine under both normoxic and hypoxic conditions, leading to the inhibition of radiation-induced G2/M arrest . Additionally, VE-821 (1 and 4 μM) enhances H2AX phosphorylation at Ser139 in OVCAR-8 cells induced by topotecan and cisplatin but does not block ATR-mediated Ser345 Chk1 or Ser296 autophosphorylation induced by gemcitabine, topotecan, or cisplatin .
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• Cell Research:
  Clonogenic survival assays were performed as described before. Briefly, logarithmically growing cells were plated in triplicate in 6-well tissue culture dishes under oxic (21% O2) or hypoxic conditions (0.5% O2) using an InVivo2 300 chamber. Cells were incubated for 6 h before irradiation under oxia or hypoxia using tightly sealed chambers. The target O2 level was achieved within 6 h of gassing and maintained during irradiation, as confirmed by an OxyLite oxygen probe. Cells irradiated under hypoxia were exposed to normoxia at 1 h post-irradiation. As standard, VE-821 (1 μM) was added 1 h prior to irradiation (6 Gy) and was washed away 72 h after irradiation. For the chemotherapy experiments, cells were initially exposed to increasing concentrations of gemcitabine (5, 10 and 20 nM) for 24 h before addition of the VE-821 (1 μM) for another 72 h. The effect of triple combination of irradiation with VE-821 and gemcitabine was examined as well. Cells were incubated for 10–21 d until colonies were stained with 0.5% crystal violet and counted in a CellCount automated colony counter. Clonogenic survival was calculated and data were fitted in GraphPad Prism 4.0 .
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ATR, ATR Inhibitor IV, ATM/ATR, ATM and RAD3 related, ATM, Ataxia telangiectasia mutated, inhibit, Inhibitor, VE 821, VE821, VE-821

Compound Identifiers

PubChem CID

51000408