Berzosertib (VE-822)

Catalog No.S7102 Batch:S710207

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Technical Data

Formula

C24H25N5O3S
Molecular Weight 463.55 CAS No. 1232416-25-9
Solubility (25°C)* In vitro DMSO 24 mg/mL (51.77 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Berzosertib (VE-822, VX970, M6620) is an ATR inhibitor with IC50 of 19 nM in HT29 cells.
Targets
ATR [1]
(HT29 cells)
19 nM
In vitro

VE-822 (80 nM) attenuates ATR signaling pathway and reduces survival in tumor cells in response to XRT and LY-188011. VE-822 (80 nM) attenuates ATR signaling in normal cells without enhancing radiation and LY-188011 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 LY-188011 enhances early and late apoptosis in PSN-1 cells that is strongest in the triple combination. [1]

VE-822 increases tumor response to DNA damaging agents associated with blockade of pChk1 Ser345. [2]
In vivo

VE-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 LY-188011 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. [1]
Features The first ATR-targeted drug candidate with high selectivity for ATR.

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    HT29 cells

  • Concentrations

    19 nM

  • Incubation Time

    24 h

  • Method

    Cells were treated with different concentrations of VE-822.
Animal Study:

[1]
  • Animal Models

    mice bearing PSN-1 or MiaPaCa-2 tumors

  • Dosages

    60 mg/kg

  • Administration

    Oral gavage

References

  • https://pubmed.ncbi.nlm.nih.gov/23222511/
  • https://pubmed.ncbi.nlm.nih.gov/23583268/

Customer Product Validation

Western blot analysis of scr or siPNUTS transfected cells without IR or 6 h after 10 Gy. VE-822 was added for 2, 5, 15, 30 or 60 min to indicated samples 6 h after 10 Gy.

Data from [ , , Nucleic Acids Res, 2018, doi:10.1093/nar/gky1233 ]

Combination treatment enhanced the DNA damage effect presented by examining fluorescence intensity of γ-H2A.X and p53 in ESCC cells. Cells treated with cisplatin, VE-822, or combination of two drugs for 24 h were fixed and co-labeled with anti-γH2AX and anti-p53 antibodies. The γ-H2A.X and p53 foci were analyzed by immunofluorescence microscopy. Combination treatment resulted in accumulation of DNA damage presented by stronger and more fluorescence staining of γ-H2AX and p53.

Data from [ , , Cancer Lett, 2018, 432:56-68 ]

Flow cytometry analysis of E14.5 FL lineage negative cells from indicated genotypes treated with ATMi (KU-55933; 1nM), ATRi (VE-822; 1nM) or both inhibitors or DMSO as a negative control for 24 hours in culture before AnnexinV and PI levels were measured.

Data from [ , , Sci Rep, 2016, 6:27379. ]

Western blot analysis for a time course experiment in the presence of wortmannin (lanes 5 to 8), VE-822 (lanes 9 to 12), or a vehicle control (lanes 1 to 4).

Data from [ , , J Virol, 2015, 89(9): 5040-59 ]

Selleck's Berzosertib (VE-822) has been cited by 147 publications

KEAP1 and STK11/LKB1 alterations enhance vulnerability to ATR inhibition in KRAS mutant non-small cell lung cancer [ Cancer Cell, 2025, 43(8):1530-1548.e9] PubMed: 40645185
Homologous recombination promotes non-immunogenic mitotic cell death upon DNA damage [ Nat Cell Biol, 2025, 27(1):59-72] PubMed: 39805921
Mouse MRE11-RAD50-NBS1 is needed to start and extend meiotic DNA end resection [ Nat Commun, 2025, 16(1):3613] PubMed: 40240347
Selective targeting of genome amplifications and repeat elements by CRISPR-Cas9 nickases to promote cancer cell death [ Nat Commun, 2025, 16(1):5126] PubMed: 40456709
The DNA replication checkpoint prevents PCNA/RFC depletion to protect forks from HLTF-induced collapse in human cells [ Mol Cell, 2025, 85(13):2474-2486.e6] PubMed: 40578346
Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response [ Mol Syst Biol, 2025, 21(3):231-253] PubMed: 39838187
TOX High-Mobility Group Box Family Member 4 promotes DNA double-strand break repair via nonhomologous end joining [ J Biol Chem, 2025, 301(6):110174] PubMed: 40328361
TEX264 drives selective autophagy of DNA lesions to promote DNA repair and cell survival [ Cell, 2024, 187(20):5698-5718.e26] PubMed: 39265577
Distinct regulation of ATM signaling by DNA single-strand breaks and APE1 [ Nat Commun, 2024, 15(1):6517] PubMed: 39112456
Radiotherapy-resistant prostate cancer cells escape immune checkpoint blockade through the senescence-related ataxia telangiectasia and Rad3-related protein [ Cancer Commun (Lond), 2024, 10.1002/cac2.12636] PubMed: 39698847

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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