BEZ235 (NVP-BEZ235)
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.
BEZ235是一种咪唑喹啉衍生物,抑制PI3K和mTOR激酶的活性,具有低纳摩尔浓度的IC50值。在临床前动物研究以及临床试验中,BEZ235有很好的耐受性,具有可控制的胃肠道副作用[1, 2]。BEZ235与ATP竞争结合激酶的ATP结合位点,可逆的降低酶活性,导致肿瘤细胞停滞在G1期[1]。除了抑制细胞生长,BEZ235还可以阻断VEGF诱导的血管生成[3]。BEZ235也可能抑制DNA-PKcs[4]。
BEZ235在体外和体内具有潜在的抗肿瘤活性。BEZ235抑制不依赖于PI3K途径突变的多个肿瘤细胞系的生长[5]。在异种移植小鼠模型中,BEZ235阻断PI3K信号,具有抗肿瘤活性[1, 5]。组合研究表明,BEZ235可以增强temozolomide的功效[1]。
临床数据表明BEZ235具有抗肿瘤活性,尤其是在PI3K信号通路失调的癌症患者中。BEZ235单独给药或与其他药剂组合给药被用于多个临床试验中。
参考文献:
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.
- 1. Wang F, Zhang J, et al. "The mTOR-glycolytic pathway promotes T-cell immunobiology in oral lichen planus." Immunobiology. 2020;225(3):151933. PMID:32201095
- 2. Li M, Li M, et al. "Remodeling tumor immune microenvironment via targeted blockade of PI3K-γ and CSF-1/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy." J Control Release. 2020;321:23–35. PMID:32035193
- 3. 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
- 4. 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
Storage | Store at -20°C |
M.Wt | 469.55 |
Cas No. | 915019-65-7 |
Formula | C30H23N5O |
Solubility | insoluble in DMSO; insoluble in EtOH; insoluble in H2O |
Chemical Name | 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)phenyl]propanenitrile |
SDF | Download SDF |
Canonical SMILES | CC(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 | 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。 |
细胞实验[1]: | |
细胞系 |
MOLT-4和CEM-R细胞 |
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. |
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 |
质量控制和MSDS
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