Berzosertib (VE-822)

製品コードS7102 バッチS710205

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 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.

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

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. [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 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. [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 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

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：

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
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
Cyclin E-induced replicative stress drives p53-dependent whole-genome duplication [ Cell, 2023, 186(3):528-542.e14] PubMed: 36681079
A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors [ Signal Transduct Target Ther, 2023, 8(1):183] PubMed: 37160887
An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress [ Nat Commun, 2023, 14(1):4991] PubMed: 37591859
An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress [ Nat Commun, 2023, 14(1):4991] PubMed: 37591859
ATR phosphorylates DHX9 at serine 321 to suppress R-loop accumulation upon genotoxic stress [ Nucleic Acids Res, 2023, 10.1093/nar/gkad973] PubMed: 37930853
Excessive transcription-replication conflicts are a vulnerability of BRCA1-mutant cancers [ Nucleic Acids Res, 2023, gkad172] PubMed: 36928661
Excessive transcription-replication conflicts are a vulnerability of BRCA1-mutant cancers [ Nucleic Acids Research, 2023, 4341–4362] PubMed: None

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。