Berzosertib (VE-822)

製品コードS7102 バッチS710207

印刷

化学情報

Chemical Structure Synonyms VX970, M6620 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H25N5O3S
分子量 463.55 CAS No. 1232416-25-9
Solubility (25°C)* 体外 DMSO 24 mg/mL (51.77 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Berzosertib (VE-822, VX970, M6620) is an ATR inhibitor with IC50 of 19 nM in HT29 cells.
in vitro

Berzosertib (VE-822) at 80 nM attenuates the ATR signaling pathway and reduces survival in tumor cells in response to XRT and LY-188011. It also attenuates ATR signaling in normal cells without enhancing radiation and LY-188011 killing in normal cells. This compound increases XRT-induced residual γH2AX and 53BP1 foci compared with XRT in MiaPaCa-2 and PSN-1 cells. Its pre-treatment decreases Rad51 foci after XRT in MiaPaCa-2 and PSN-1 cells. Alone, it increases the G1-phase-fraction in MiaPaCa-2 and PSN-1 cells. It abrogates XRT enriched G2/M-phase-fraction in MiaPaCa-2 and PSN-1 cells. VE-822 has little effect alone, while combined with XRT and/or LY-188011, it enhances early and late apoptosis in PSN-1 cells that is strongest in the triple combination. [1]

It increases tumor response to DNA damaging agents associated with blockade of pChk1 Ser345. [2]
in vivo

Berzosertib (VE-822) at 60 mg/kg inhibits phospho-Ser-345-Chk1 in mice bearing PSN-1 tumors after DNA-damaging agents. Combined with XTR, it doubles the time for tumors to grow to 600 mm3 of XRT alone in mice bearing both PSN-1 and MiaPaCa-2 tumors. When added to the combination of LY-188011 and XRT, this compound substantially prolongs the tumor growth delay compared with the Gem+XRT1 group in mice bearing both PSN-1 tumors. It also increases uptake in tumors by 44% compared with XRT1 when combined with XRT1, suggesting that its addition increased γH2AX phosphorylation and persistence of DNA damage caused by XRT. [1]
特徴 The first ATR-targeted drug candidate with high selectivity for ATR.

プロトコル(参考用のみ)

細胞アッセイ 細胞株 HT29 cells
濃度 19 nM
反応時間 24 h
実験の流れ

Cells were treated with different concentrations of Berzosertib (VE-822).
動物実験 動物モデル mice bearing PSN-1 or MiaPaCa-2 tumors
投薬量 60 mg/kg
投与方法 Oral gavage

参考

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

カスタマーフィードバック

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.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
Homologous Repair-Deficient Pancreatic Cancer: Refined Targeting of DNA Damage Response is an Effective Therapeutic Strategy [ United Eur Gastroent, 2025, 13(7):1328-1342] PubMed: 40823818
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
Inhibiting the DNA damage repair of HNSCC cells in combination with normo-fractionated radiotherapy influences clonogenicity, senescence and expression of NK cell activation markers [ Sci Rep, 2025, 15(1):31827] PubMed: 40883442
TEX264 drives selective autophagy of DNA lesions to promote DNA repair and cell survival [ Cell, 2024, 187(20):5698-5718.e26] PubMed: 39265577

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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