Berzosertib (VE-822)

Catalog No.S7102 Batch:S710205

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Technical Data

Formula

C24H25N5O3S
Molecular Weight 463.55 CAS No. 1232416-25-9
Solubility (25°C)* In vitro DMSO 92 mg/mL (198.46 mM)
Water Insoluble
Ethanol Insoluble
* <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

Customer Product Validation

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

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

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

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

Selleck's Berzosertib (VE-822) has been cited by 129 publications

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
The MYCN oncoprotein is an RNA-binding accessory factor of the nuclear exosome targeting complex [ Mol Cell, 2024, S1097-2765(24)00285-5] PubMed: 38703770
SIRT2 promotes base excision repair by transcriptionally activating OGG1 in an ATM/ATR-dependent manner [ Nucleic Acids Res, 2024, gkae190] PubMed: 38554113
DNA damage remodels the MITF interactome to increase melanoma genomic instability [ Genes Dev, 2024, 38(1-2):70-94] PubMed: 38316520
Base-excision repair pathway regulates transcription-replication conflicts in pancreatic ductal adenocarcinoma [ Cell Rep, 2024, 43(10):114820] PubMed: 39368091
Embryonic stem cells maintain high origin activity and slow forks to coordinate replication with cell cycle progression [ EMBO Rep, 2024, 10.1038/s44319-024-00207-5] PubMed: 39054377
Methylation of NRIP3 Is a Synthetic Lethal Marker for Combined PI3K and ATR/ATM Inhibitors in Colorectal Cancer [ Clin Transl Gastroen, 2024, 15(3):e00682] PubMed: 38235705
The MRE11-RAD50-NBS1 complex both starts and extends DNA end resection in mouse meiosis [ bioRxiv, 2024, 2024.08.17.608390] PubMed: 39185212
MGMT function determines the differential response of ATR inhibitors with DNA-damaging agents in glioma stem cells for GBM therapy [ Neurooncol Adv, 2024, 6(1):vdad165] PubMed: 38213834

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.