VE-821
(Synonyms: 3-氨基-6-[4-(甲基磺酰基)苯基]-N-苯基-2-吡嗪甲酰胺) 目录号 : GC10293
An inhibitor of ATR
Cas No.:1232410-49-9
Sample solution is provided at 25 µL, 10mM.
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VE-821 is a potent, highly-selective, and ATP-competitive DNA damage response (DDR) kinase ATR inhibitor with Ki value of 13nM. VE-821 specifically inhibits ATR, revealing low cross-reactivity against the mammalian target of rapamycin (mTOR), DNA-dependent protein kinase (DNA-PK), phosphoinositol 3-kinase-γ (PI3K) and the related PIKKs ATM [1].
HL-60 cells treated with VE-821 (10μM) showed reduction of phosphorylatin of Chk1 (Ser 345), inhibition of cell growth, and a radiosensitizing effect after Gamma-ray irradiation [2].
VE-821 has also been demonstrated to down-regulate the phosphorylated Chk1 (Ser 345) but it does not inhibit the phosphorylation of Chk2 (Thr68) and ATM (Ser1981) in pancreatic cancer cell lines, including PSN-1 and MiaPaCa-2 cells that are treated with gemcitabine or radiation. VE-821 combined with gemcitabine (a nucleoside analog) has caused a remarkable increase of cytotoxic effect of gemcitabine against hypoxia [3].
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 Chem Biol. 2011 Apr 13;7(7):428-30.
[2] Vávrová J1, Zárybnická L, Lukášová E, Řezáčová M, Novotná E, Sinkorová Z, Tichý A, Pejchal J, Durišová 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.
| Kinase experiment [1]: | |
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Inhibitory activities |
VE-821 (2 μM) was screened against the indicated human (h), rat (r), mouse (m) and fission yeast (y) kinases using the Millipore KinaseProfiler service, at ATP concentrations equal to each enzyme’s ATP Km. |
| Cell experiment [1]: | |
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Cell lines |
HFL1 cells; HCT116 cancer cells; H23 cancer cell line. |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
10 μM; 24, 48 or 96 h. |
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Applications |
HFL1 cells were pretreated with 10 μM VE-821 or DMSO before addition of 200 μM cisplatin (Cis), 1 μM gemcitabine (Gem), 100 μM etoposide (Etop) or 5 Gy ionizing radiation (IR), VE-821 blocks Chk1 Ser345 phosphorylation under all conditions and inhibits H2AX phosphorylation in treatment with cisplatin and gemcitabine. In the H23 cancer cell line, VE-821 shows marked synergy with cisplatin in growth arrest. |
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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 Chem Biol, 2011, 7(7): 428-430. | |
| Cas No. | 1232410-49-9 | SDF | |
| 别名 | 3-氨基-6-[4-(甲基磺酰基)苯基]-N-苯基-2-吡嗪甲酰胺 | ||
| 化学名 | 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 | ||
| Canonical SMILES | CS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C(=O)NC3=CC=CC=C3)N | ||
| 分子式 | C18H16N4O3S | 分子量 | 368.41 |
| 溶解度 | ≥ 62.5mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7144 mL | 13.5718 mL | 27.1437 mL |
| 5 mM | 0.5429 mL | 2.7144 mL | 5.4287 mL |
| 10 mM | 0.2714 mL | 1.3572 mL | 2.7144 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet