Berzosertib (VE-822)

製品コードS7102 バッチS710203

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 36 mg/mL (77.66 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 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]
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：

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

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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