VE-821
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
VE-821是一种有效的、高选择性的和ATP竞争性的DNA损伤响应激酶ATR抑制剂，Ki值为13 nM。VE-821特异性地抑制ATR，与mTOR、DNA依赖性蛋白激酶（DNA-PK）、磷酸肌醇3-激酶γ（PI3K）和相关的PIKKs ATM具有低交叉反应性[1]。
在HL-60细胞中，VE-821 (10 μM) 减少Chk1 （Ser 345）的磷酸化，抑制细胞生长，并具有放射增敏作用[2]。在胰腺癌细胞系（包括gemcitabine或放射处理的PSN-1和MiaPaCa-2细胞）中，VE-821下调磷酸化的Chk1 (Ser 345)，但不能抑制Chk2 (Thr68)和ATM (Ser1981)的磷酸化。VE-821与gemcitabine（核苷类似物）联合使用显著增加gemcitabine抗缺氧的细胞毒性效应[3]。
参考文献：
[1] Reaper PM1, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA, Golec JM, Pollard JR. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol. 2011 Apr 13; 7(7):428-30.
[2] Vávrová J1, Zárybnická L, Luká?ová E, ?ezá?ová M, Novotná E, Sinkorová Z, Tichy A, Pejchal J, Duri?ová K. Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60). Radiat Environ Biophys. 2013 Nov; 52(4):471-9.
[3] Prevo R1, Fokas E, Reaper PM, Charlton PA, Pollard JR, McKenna WG, Muschel RJ, Brunner TB. The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy. Cancer Biol Ther. 2012 Sep; 13(11):1072-81.
- 1. Jinghua Yu, Wenyan Zhang, et al. "Regulation of host factor γ-H2AX level and location by enterovirus A71 for viral replication." Virulence. 2022 Dec;13(1):241-257. PMID:35067196
- 2. Yahya Benslimane, Thierry Bertomeu, et al. "Genome-Wide Screens Reveal that Resveratrol Induces Replicative Stress in Human Cells." Molecular Cell; Available online 4 August 2020.
- 3. Shaj K, Hutcherson RJ, et al. "ATR Kinase Activity Limits Mutagenesis and Promotes the Clonogenic Survival of Quiescent Human Keratinocytes Exposed to UVB Radiation." Photochem Photobiol. 2019 Sep 25. PMID:31554014
- 4. Jennifer Risso-Ballester, Rafael Sanjuán. "High Fidelity Deep Sequencing Reveals No Effect of ATM, ATR, and DNA-PK Cellular DNA Damage Response Pathways on Adenovirus Mutation Rate." Viruses 2019, 11(10), 938.
- 5. KAVYA SHAJ. "DIFFERING FUNCTIONS OF ATR KINASE IN HUMAN EPIDERMAL KERATINOCYTES EXPOSED TO ULTRAVIOLET B RADIATION." Wright State University. 2019.
- 6. Li Z, Liu B, et al. "hDNA2 nuclease/helicase promotes centromeric DNA replication and genome stability." EMBO J. 2018 May 17. pii: e96729. PMID:29773570
- 7. Nanda Kumar Sasi, Flavie Coquel, et al. "DDK has a primary role in processing stalled replication forks to initiate downstream checkpoint signaling." bioRxiv. 2017.October 21.
| Storage | Store at -20°C |
| M.Wt | 368.41 |
| Cas No. | 1232410-49-9 |
| Formula | C18H16N4O3S |
| Solubility | ≥62.5 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
| Chemical Name | 2-(aminomethyl)-6-[4,6-diamino-3-[4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol;sulfuric acid |
| SDF | Download SDF |
| Canonical SMILES | CS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C(=O)NC3=CC=CC=C3)N |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 激酶实验 [1]: | |
|
抑制活性 |
使用Millipore KinaseProfiler服务研究VE-821（2μM）对指定的人（h）、大鼠（r）、小鼠（m）和裂殖酵母（y）激酶的活性，ATP浓度等于每种酶ATP的Km值。 |
| 细胞实验[1]: | |
|
细胞系 |
HFL1细胞， HCT116肿瘤细胞，H23癌细胞系 |
|
溶解方法 |
该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液，一般步骤如下：请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
|
反应条件 |
10 μM，24、48或96 小时 |
|
实验结果 |
在加入200 μM顺铂（Cis）、1 μM吉西他滨（Gem）、100μM依托泊苷（Etop）或5Gy电离辐射（IR）之前，使用10 μM VE-821或DMSO预处理HFL1细胞，在所有条件下，VE-821阻断Chk1Ser345 磷酸化，并且在用cisplatin和gemcitabine治疗中抑制H2AX磷酸化。在H23癌细胞系中，VE-821与cisplatin协同作用，在生长停滞中发挥显著作用。 |
|
References: [1]. Reaper PM1, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA, Golec JM, Pollard JR. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat ChemBiol, 2011, 7(7): 428-430. |
|
| 描述 | VE-821是一种有效的、选择性的和ATP竞争性的ATR激酶抑制剂，Ki/IC50值分别为13 nM/26 nM。 | |||||
| 靶点 | ATR | |||||
| IC50 | 13 nM/26 nM (Ki/IC50) | |||||
质量控制和MSDS
- 批次:
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