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Etoposide

现货
Catalog No.
A1971
拓扑异构酶II(Topo II)抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
100mg
¥ 500.00
现货

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Background

Etoposide (VP-16) is the first agent recognized as a topoisomerase II inhibitor of anticancer drug with IC50 of 59.2 μM.

The activity of the topoisomerase II enzyme on re-ligation of DNA strands is interrupted by etoposide. A ternary complex with DNA is formed by etoposide, and causes DNA strands to break [1]. The enzyme was more important in cancer cell than healthy cells, because cancer cells divided more rapidly. So etoposide induced apoptosis of the cancer cells [2]. Etoposide exhibited cytotoxic activity against HepG2 and MOLT-3 cancer cells with IC50 of 30.16 μM and 0.051μM [3]. The IC50 values of etoposide against the tumor cell lines of BGC-823, HeLa, and A549 were 43.74 ± 5.13, 209.90 ± 13.42, and 139.54 ± 7.05 μM, respectively [4].

References:
[1]. Pommier Y, Leo E, Zhang H, Marchand C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol. 2010 May 28;17(5):421-33.
[2]. Gordaliza M, García PA, del Corral JM, Castro MA, Gómez-Zurita MA. Podophyllotoxin: distribution, sources, applications and new cytotoxic derivatives. Toxicon. 2004 Sep 15;44(4):441-59.
[3]. Pingaew R, Mandi P, Nantasenamat C, Prachayasittikul S, Ruchirawat S, Prachayasittikul V. Design, synthesis and molecular docking studies of novel N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-based triazoles with potential anticancer activity. Eur J Med Chem. 2014 May 6;81C:192-203.
[4]. Xiao L, Zhao W, Li HM, Wan DJ, Li DS, Chen T, Tang YJ. Design and synthesis of the novel DNA topoisomerase II inhibitors: Esterification and amination substituted 4'-demethylepipodophyllotoxin derivates exhibiting anti-tumor activity by activating ATM/ATR signaling pathways. Eur J Med Chem. 2014 Jun 10;80:267-77.

文献引用

1. Barot S, Abo-Ali EM, et al. "Inhibition of glycogen catabolism induces intrinsic apoptosis and augments multikinase inhibitors in hepatocellular carcinoma cells." Exp Cell Res. 2019 Aug 15;381(2):288-300. PMID:31128107
2. Rogers C, Erkes DA, et al. "Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation." Nat Commun. 2019 Apr 11;10(1):1689. PMID:30976076
3. Wu Q, Wei X, et al. "Bionic 3D spheroids biosensor chips for high-throughput and dynamic drug screening." Biomed Microdevices. 2018 Sep 15;20(4):82. PMID:30220069
4. Lochmann TL, Floros KV, et al. "Venetoclax Is Effective in Small-Cell Lung Cancers with High BCL-2 Expression." Clin Cancer Res. 2018 Jan 15;24(2):360-369. PMID:29118061
5. Xia L, Xiao X, et al. "Coactosin-like protein CLP/Cotl1 suppresses breast cancer growth through activation of IL-24/PERP and inhibition of non-canonical TGFβ signaling." Oncogene. 2018 Jan 18;37(3):323-331. PMID:28925397

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt588.56
Cas No.33419-42-0
FormulaC29H32O13
Solubility≥29.45mg/mL in DMSO
Chemical Name(5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one
SDFDownload SDF
Canonical SMILESCC1OCC2C(O1)C(C(C(O2)OC3C4COC(=O)C4C(C5=CC6=C(C=C35)OCO6)C7=CC(=C(C(=C7)OC)O)OC)O)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

激酶实验 [1]:

拓扑异构酶II活性测定

制备核提取物并将细胞核分离。以去连环百分比计算拓扑异构酶II活性。氚标记的含动基体DNA(KDNA 0.22 μg)作为底物。将Etoposide和拓扑异构酶II置于37℃孵育30分钟,再使用1%十二烷基硫酸钠(SDS)和蛋白酶K(100 μg/mL)终止反应。测得Etoposide对拓扑异构酶II的抑制和去连环百分比。

细胞实验 [2]:

细胞系

BGC-823细胞、HeLa细胞和A549细胞

制备方法

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

0.5, 1, 10, 20, 50, 100, 200和500 μM;2天

试验结果

Etoposide对肿瘤细胞系BGC-823、HeLa以及A549的IC50值分别为43.74 ± 5.13 μM、209.90 ± 13.42 μM和139.54 ± 7.05 μM。

动物实验 [3]:

动物模型

鼠血管肉瘤细胞ISOS-1异种移植模型

给药剂量

2.5, 5, 10 mg/kg;腹腔注射;每天1次,持续5天

实验结果

腹腔注射10 mg/kg Etoposide能抑制鼠血管肉瘤细胞ISOS-1肿瘤。

其他注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Beauchesne P, Bertrand S, N'guyen MJ, Christianson T, Dore JF, Mornex F, Bonner JA. Etoposide sensitivity of radioresistant human glioma cell lines. Cancer Chemother Pharmacol. 1998;41(2):93-7.

[2]. Xiao L, Zhao W, Li HM, Wan DJ, Li DS, Chen T, Tang YJ. Design and synthesis of the novel DNA topoisomerase II inhibitors: Esterification and amination substituted 4'-demethylepipodophyllotoxin derivates exhibiting anti-tumor activity by activating ATM/ATR signaling pathways. Eur J Med Chem. 2014 Jun 10;80:267-77.

[3]. Ma G1, Masuzawa M, Hamada Y, Haraguchi F, Tamauchi H, Sakurai Y, Fujimura T, Katsuoka K. Treatment of murine angiosarcoma with etoposide, TNP-470 and prednisolone. J Dermatol Sci. 2000 Nov;24(2):126-33.

质量控制

化学结构

Etoposide

相关生物数据

Etoposide

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Etoposide

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Etoposide

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Etoposide