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

VE-822 (Synonyms: VX-970)

Cat. No.: HY-13902 Purity: 99.22%
Data Sheet SDS Handling Instructions

VE-822 is an ATR inhibitor with Ki value of <0.2 nM, also inhibits ATM with Ki of 34 nM.

For research use only. We do not sell to patients.
VE-822 Chemical Structure

VE-822 Chemical Structure

CAS No. : 1232416-25-9

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10 mM * 1 mL in DMSO $77 In-stock
5 mg $70 In-stock
10 mg $95 In-stock
50 mg $240 In-stock
100 mg $450 In-stock
200 mg $650 In-stock
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    VE-822 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.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    VE-822 is an ATR inhibitor with Ki value of <0.2 nM, also inhibits ATM with Ki of 34 nM.

    IC50 & Target

    Ki: <0.2 nM (ATR), 34 nM (ATM)[1]
    IC50: 19 nM (ATR, in PSN-1 and MiaPaCa-2 cells), 2.6 μM (ATM, in PSN-1 and MiaPaCa-2 cells)[1]

    In Vitro

    VE-822 also inhibits DNK-PA, mTOR, PI3Kγ with IC50 of >4, >1, and 0.22 μM, respectively. In PSN-1 and MiaPaCa-2 cells, VE-822 inhibits ATR and ATM with IC50 of 19 nM and 2.6 μM, respectively. VE-822 (80 nM) reduces phospho-Ser345-Chk1 after Gemcitabine (100 nM), radiation (XRT) (6 Gy) or both in PDAC. Additionally, VE-822 does not inhibit ATM, Chk2 or DNA-PK phosphorylation in response to radiation, which further supports the selectivity of VE-822 for ATR. VE-822 decreases survival of irradiated PDAC (all lines used are p53-mutant; K-Ras mutant). Knock down of Chk1 by siRNA sensitizes PSN-1 and MiaPaCa-2 cells to radiation but the radiosensitising effect is less profound compare with VE-822. Adding VE-822 to Gemcitabine reduces survival ~2-3-fold and dramatically more after chemoradiotherapy[1].

    In Vivo

    PSN-1 xenografts are treated with VE-822 (60 mk/kg; d0, 1), Gemcitabine (100 mg/kg; d0) and/or XRT (6 Gy; d1). Tumors are then harvested 2 h post-XRT. VE-822 inhibits p-Ser-345-Chk1 in xenografts after DNA-damaging agents, establishing VE-822 as a potent inhibitor of ATR in vivo. Besides, VE-822 enhances the therapeutic efficacy of radiation (XRT) in MiaPaCa-2 and PSN-1 xenograft models[1].

    Clinical Trial
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    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 2.1573 mL 10.7863 mL 21.5726 mL
    5 mM 0.4315 mL 2.1573 mL 4.3145 mL
    10 mM 0.2157 mL 1.0786 mL 2.1573 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [1]

    VE-822 is dissolved in DMSO and stored, and then diluted with appropriate media before use[1].

    Gemcitabine (10 nM) is added 24 h pre-XRT and is replaced with fresh medium before addition of VE-822. PSN-1 cells are treated with VE-822 (80 nM) for 1 h before, through to 18 h after, XRT (6 Gy). Apoptosis is analyzed 48 h after XRT by flow cytometry using an Annexin V-FITC kit with PI[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    VE-822 is dissolved in 10% Vitamin E d-alpha tocopheryl polyethylene glycol 1000 succinate and administered by gavage, in 200 μL (Mice)[1].

    Mice[1]
    MiaPaCa-2 cells and PSN-1 cells (106 in 50 μL serum-free medium mixed with 50 μL of Matrigel) are inoculated subcutaneously in female Balb/c nude mice. When the xenograft tumors reach 80 mm3, the mice are randomized. VE-822 (60 mg/kg) is administered by oral gavage on one of three alternate schedules; either daily on days 0-5 (total of six days dosing), daily on days 0 through to 3 (total of 4 days dosing) or on days 1, 3 and 5. XRT (6 Gy) is given either on days 0 or 1 or days 1-5 (total of 5 days dosing; 2 Gy). Gemcitabine is dosed at 100 mg/kg by intraperitoneal injection on day 0. XRT to the tumor is given 2 h after initiation of VE-822 treatment. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    463.55

    Formula

    C₂₄H₂₅N₅O₃S

    CAS No.

    1232416-25-9

    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

    DMSO: ≥ 35 mg/mL

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

    Purity: 99.22%

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    VE-822
    Cat. No.:
    HY-13902
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