1. Cell Cycle/DNA Damage
    PI3K/Akt/mTOR
  2. ATM/ATR

VE-821 

Cat. No.: HY-14731 Purity: 99.47%
Handling Instructions

VE-821 is a potent ATP-competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM.

For research use only. We do not sell to patients.
VE-821 Chemical Structure

VE-821 Chemical Structure

CAS No. : 1232410-49-9

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 92 In-stock
5 mg USD 84 In-stock
10 mg USD 144 In-stock
50 mg USD 348 In-stock
100 mg USD 588 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

    VE-821 purchased from MCE. Usage Cited in: University of Gothenburg. 2016.

    ATRi however only reduces the phosphorylation of CHK1, but not of 4EBP1 or S6, validating our hypothesis.

    VE-821 purchased from MCE. Usage Cited in: Oncogene. 2016 Sep 8;35(36):4689-97.

    Western blotting analysis of lysates from λ820 cells treated with vehicle (0.1% DMSO), 10 μM of the ATR inhibitor VE-821, 1 μM of ATR inhibitor AZ20, 1 μM PI3K/mTOR inhibitor NVP-BEZ235 or indicated concentrations of PI3K/mTOR inhibitor GSK1059615.

    VE-821 purchased from MCE. Usage Cited in: DNA Repair (Amst). 2016 Mar 3;40:35-46.

    Impact of ATR inhibition on DNA damage response, γ-H2Ax foci formation and cytotoxicity: A representative immunoblot with vinculin used as a loading control(A) shows the impact of ATR inhibition (VE-821) on the early (0.5 h) and late (24 h) DDR to the indicated treatments in H460 cells. pATM fold change shown above the immunoblot (A).

    VE-821 purchased from MCE. Usage Cited in: Eur J Med Chem. 2017 Feb 15;127:691-702.

    Relative cell viability (%) in MDCK CAIX- and CAIX+ cells exposed to ATR inhibitors (VE-821 and VE-822) or the CAIXi conjugated derivatives in combination with radiation during normoxia (21% O2) and anoxia (≤0.02% O2). Normoxic cells are irradiated with 2 Gy and anoxic cells with 4 Gy to induce similar effects on cell viability.

    VE-821 purchased from MCE. Usage Cited in: Front Oncol. 2017 May 19;7:98.

    ATM inhibition by treatment with KU-55933 (10 µM) strongly reduces HR efficiency in JJN3-HR and U266-HR, although cells are still able to perform HR to some extent.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    VE-821 is a potent ATP-competitive inhibitor of ATR with Ki/IC50 of 13 nM/26 nM.

    IC50 & Target

    Ki: 13 nM (ATR)[1]
    IC50: 26 nM (ATR)[2]

    In Vitro

    VE-821 shows excellent selectivity for ATR with minimal cross-reactivity against the related PIKKs ATM, DNA-PK, mTOR and PI3Kγ (Kis of 16 μM, 2.2 μM, >1 μM and 3.9 μM, respectively) and against a large panel of unrelated protein kinases[1]. VE-821 (compound 27) also inhibits ATM and DNA-PK wirh IC50 of >8 μM, and 4.4 μM, respectively[2]. VE-821 significantly enhances the sensitivity of PSN-1, MiaPaCa-2 and primary PancM pancreatic cancer cells to radiation and Gemcitabine under both normoxic and hypoxic conditions. ATR inhibition by VE-821 leads to inhibition of radiation-induced G2/M arrest in cancer cells. In both PSN-1 and MiaPaCa-2 cells, 1 µM VE-821 inhibits phosphorylation of Chk1 (Ser 345) after treatment with Gemcitabine (100 nM), radiation (6 Gy) or both, at 2 h post-irradiation[3].

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.7144 mL 13.5718 mL 27.1437 mL
    5 mM 0.5429 mL 2.7144 mL 5.4287 mL
    10 mM 0.2714 mL 1.3572 mL 2.7144 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [2]

    The ability of compounds (e.g., VE-821) to inhibit ATR, ATM or DNAPK kinase activity is tested using a radiometric-phosphate incorporation assay. A stock solution is prepared consisting of the appropriate buffer, kinase, and target peptide. To this is added the compound of interest, at varying concentrations in DMSO to a final DMSO concentration of 7%. Assays are initiated by addition of an appropriate [g-33P]ATP solution and incubated at 25°C. Assays are stopped, after the desired time course, by addition of phosphoric acid and ATP to a final concentration of 100 mM and 0.66 μM, respectively. Peptides are captured on a phosphocellulose membrane, prepared, and washed six times with 200 μL of 100 mM phosphoric acid, prior to the addition of 100 μL of scintillation cocktail and scintillation counting on a 1450 Microbeta Liquid Scintillation Counter. Dose−response data are analyzed using GraphPad Prism software[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [3]

    VE-821 is dissolved in DMSO and stored, and then diluted with appropriate media before use[3].

    MiaPaCa-2, PSN-1 and Panc1 cells (5×104) are plated in 96-well plates and after 4 h treated with increasing concentrations of VE-821 at 1 h before irradiation with a single dose of 4 Gy. Medium is replaced 72 h post-irradiation at which point viability is measured using the using the Alamar Blue assay. Cells are allowed to proliferate and cell viability is again analyzed at day 10 for the different treatment conditions. Cell viability and surviving fraction are normalized to the untreated (control) group[3]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    368.41

    Formula

    C₁₈H₁₆N₄O₃S

    CAS No.

    1232410-49-9

    SMILES

    O=C(NC1=CC=CC=C1)C2=NC(C3=CC=C(C=C3)S(=O)(C)=O)=CN=C2N

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    10 mM in DMSO

    VE-821 is prepared im vehicle (10% PEG300, 2.5% Tween-80, pH 4)[4].

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    References

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    Cat. No.:
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