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BEZ235 (NVP-BEZ235)

现货
Catalog No.
A8246
ATP竞争性的PI3K/mTOR抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 500.00
现货
100mg
¥ 880.00
现货
500mg
¥ 2,800.00
现货

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Background

BEZ235 is an imidazoquinoline derivative inhibiting both PI3K and mTOR kinases with low nanomolar IC50s. It was well tolerated in preclinical animal studies as well as in clinical trials with manageable gastrointestinal side-effects[1, 2]. It competes with ATP by binding to the ATP-binding site of kinases and reversibly reduces enzyme activity, resulting in growth arrest of tumor cells in G1 phase[1]. Besides the inhibition of cell growth, BEZ235 blocks VEGF-induced angiogenesis[3]. It may also inhibit DNA-PKcs[4].

BEZ235 has shown potential anti-tumor activity both in vitro and in vivo. It inhibited growth of multiple cancer cell lines independently of mutation status in PI3K pathway[5]. In xenograft mice models, it blocked PI3K signaling and showed antitumor activity[1, 5]. Combination study demonstrated that it enhances the efficacy of temozolomide[1].

Clinical data shows anti-tumor activity of BEZ235 treatment, especially in cancer patients with deregulated PI3K signaling pathway. This compound is currently under investigation in multiple clinical trials either as monotherapy or in combination with other agents.

References:
1. Maira SM, Stauffer F, Brueggen J et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther 2008; 7: 1851-1863.
2. Markman B, Tabernero J, Krop I et al. Phase I safety, pharmacokinetic, and pharmacodynamic study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors. Ann Oncol 2012; 23: 2399-2408.
3. Schnell CR, Stauffer F, Allegrini PR et al. Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging. Cancer Res 2008; 68: 6598-6607.
4. Mukherjee B, Tomimatsu N, Amancherla K et al. The dual PI3K/mTOR inhibitor NVP-BEZ235 is a potent inhibitor of ATM- and DNA-PKCs-mediated DNA damage responses. Neoplasia 2012; 14: 34-43.
5. Serra V, Markman B, Scaltriti M et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res 2008; 68: 8022-8030.

文献引用

1. Sun S, Zhang Y, et al. "HDAC6 inhibitor TST strengthens the antiproliferative effects of PI3K/mTOR inhibitor BEZ235 in breast cancer cells via suppressing RTK activation." Cell Death Dis. 2018 Sep 11;9(9):929. PMID:30206202
2. Peng T, Dou QP. "Everolimus Inhibits Growth of Gemcitabine-Resistant Pancreatic Cancer Cells via Induction of Caspase-Dependent Apoptosis and G(2) /M Arrest." J Cell Biochem. 2017 Feb 6. PMID:28165150

Chemical Properties

StorageStore at -20°C
M.Wt469.55
Cas No.915019-65-7
FormulaC30H23N5O
Solubility≥7.8mg/mL in DMSO, <2.81 mg/mL in EtOH, <2.84 mg/mL in H2O
Chemical Name2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)phenyl]propanenitrile
SDFDownload SDF
Canonical SMILESCC(C)(C#N)C1=CC=C(C=C1)N2C3=C4C=C(C=CC4=NC=C3N(C2=O)C)C5=CC6=CC=CC=C6N=C5
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

细胞实验[1]:

细胞系

MOLT-4和CEM-R细胞

溶解方法

在DMSO中的溶解度<10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

细胞周期抑制:500 nM;pRb减少:200 nM,16 h

应用

在MOLT-4和CEM-R细胞系中,对BEZ235处理16小时的PI染色的T-ALL细胞进行流式细胞分析表明G0/G1期细胞增加,同时S和G2-M期细胞数量减少。200 nmol/L NVP-BEZ235处理16小时的MOLT-4和CEM-R细胞中,Ser807/811 pRb的量降低,而总的pRb水平保持不变。

动物实验[2]:

动物模型

植入BT474-VH2细胞的雌性无胸腺nude-Foxn1nu小鼠

剂量

40 mg/kg,1次/天,21天;口服给药

应用

在工程表达H1047R热点突变或空载体(pBABE)的HER2扩增BT474乳腺癌细胞衍生的异种移植模型中评估BEZ235的抗肿瘤活性,BEZ235导致肿瘤生长抑制。与模拟对照相比,BEZ235对H1047R过表达的肿瘤具有更好的效果。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Chiarini F, Grimaldi C, Ricci F, et al. Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemia. Cancer research, 2010, 70(20): 8097-8107.

[2] Serra V, Markman B, Scaltriti M, et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer research, 2008, 68(19): 8022-8030.

生物活性

描述 BEZ235 (NVP-BEZ235)是一种ATP竞争性的PI3K和mTOR双重抑制剂,作用于p110α/γ/δ/β和mTOR(p70S6K),IC50值分别为4 nM/5 nM/7 nM/75 nM/6 nM。
靶点 p110α p110γ p110δ p110β ATR  
IC50 4 nM 5 nM 7 nM 75 nM 21 nM  

质量控制

化学结构

BEZ235 (NVP-BEZ235)

相关生物数据

BEZ235 (NVP-BEZ235)
NVP-BEZ235 (0.2 μM) inhibits phosphorylation of the mammalian target of rapamycin (mTOR) target 4EBP1 in both monolayer and spheroid cultures. Lysates were prepared after 24h of treatment and subjected to Western blotting using the indicated antibodies.

相关生物数据

BEZ235 (NVP-BEZ235)

相关生物数据

BEZ235 (NVP-BEZ235)

相关生物数据

BEZ235 (NVP-BEZ235)

相关生物数据

BEZ235 (NVP-BEZ235)