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    Berzosertib (VE-822; VX-970)
    Berzosertib (VE-822; VX-970)

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    This product is for research use only, not for human use. We do not sell to patients.
    Number: - + Pieces(InventoryPieces)
    InvivoChem Cat #: V2529
    CAS #: 1232416-25-9Purity ≥98%

    Description: This product is discontinued due to commercial reason,Berzosertib (VE-822; VX-970; M6620) is a specific ATR inhibitor with IC50 of 19 nM in HT29 cells. VE-822 inhibited ATR in vitro and in vivo. VE-822 decreased maintenance of cell-cycle checkpoints, increased persistent DNA damage and decreased homologous recombination in irradiated cancer cells. VE-822 decreased survival of pancreatic cancer cells but not normal cells in response to XRT or gemcitabine. VE-822 markedly prolonged growth delay of pancreatic cancer xenografts after XRT and gemcitabine-based chemoradiation without augmenting normal cell or tissue toxicity. These findings support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC. 

    References: Cell Death Dis. 2012 Dec 6;3:e441.

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    Molecular Weight (MW)463.55
    CAS No.1232416-25-9
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 36 mg/mL (77.66 mM)
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    Other info

    Chemical Name: 5-(4-(isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine.


    InChi Code: InChI=1S/C24H25N5O3S/c1-15(2)33(30,31)19-10-8-18(9-11-19)21-14-27-24(25)23(28-21)22-12-20(29-32-22)17-6-4-16(5-7-17)13-26-3/h4-12,14-15,26H,13H2,1-3H3,(H2,25,27)

    SMILES Code: NC1=NC=C(C2=CC=C(S(=O)(C(C)C)=O)C=C2)N=C1C3=CC(C4=CC=C(CNC)C=C4)=NO3


    VE822; VE-822; VE 822; M6620; M-6620; M 6620; VX970; VX-970; VX 970

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    In Vitro

    In vitro activity: VE-822 (80 nM) attenuates ATR signaling pathway and reduces survival in tumor cells in response to XRT and gemcitabine. VE-822 (80 nM) attenuates ATR signaling in normal cells without enhancing radiation and gemcitabine killing in normal cells. VE-822 (80 nM) increases XRT-induced residual γH2AX and 53BP1 foci compared with XRT in MiaPaCa-2 and PSN-1 cells. VE-822 (80 nM) pre-treatment decreases Rad51 foci after XRT in MiaPaCa-2 and PSN-1 cells. VE-822 (80 nM) alone increases the G1-phase-fraction in MiaPaCa-2 and PSN-1 cells. VE-822 (80 nM) abrogates XRT enriched G2/M-phase-fraction in MiaPaCa-2 and PSN-1 cells. VE-822 has little effect alone, while VE-822 (80 nM) combined with XRT and/or gemcitabine enhances early and late apoptosis in PSN-1 cells that is strongest in the triple combination. VE-822 increases tumor response to DNA damaging agents associated with blockade of pChk1 Ser345.

    Kinase Assay: Berzosertib is an ATR inhibitor with a Ki value of less than 0.2 nM. It also inhibits ATM with a Ki of 34 nM.

    Cell Assay: NSC 613327 (10 nM) is added 24 h pre-XRT and is replaced with fresh medium before addition of Berzosertib (VE-822). PSN-1 cells are treated with Berzosertib (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 P.

    In VivoVE-822 (60 mg/kg) inhibits phospho-Ser-345-Chk1 in mice bearing PSN-1 tumors after DNA-damaging agents. VE-822 (60 mg/kg) combined with XTR doubles the time for tumors to grow to 600 mm3 of XRT alone in mice bearing both PSN-1 and MiaPaCa-2 tumors. VE-822 (60 mg/kg) added to the combination of gemcitabine and XRT substantially prolongs the tumor growth delay compared with the Gem+XRT1 group n mice bearing both PSN-1 tumors. VE-822 (60 mg/kg) combined with XRT1 increases uptake in tumors by 44% compared with XRT1, suggesting that addition of VE-822 increased γH2AX phosphorylation and persistence of DNA damage caused by XRT.
    Animal modelMice bearing PSN-1 or MiaPaCa-2 tumors
    Formulation & DosageDissolved in saline; 60 mg/kg; Oral administration

    Cell Death Dis. 2012 Dec 6;3:e441.

    These protocols are for reference only. InvivoChem does not independently validate these methods.



    VE-822 attenuates ATR signaling pathway and reduces survival in tumor cells in response to XRT and gemcitabine.  2012 Dec 6;3:e441.


    VE-822 attenuates ATR signaling in normal cells without enhancing radiation and gemcitabine killing in normal cells.  2012 Dec 6;3:e441.



    Effect of VE-822 on 53BP1, γH2AX and Rad51 foci formation.  2012 Dec 6;3:e441.


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