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Dactolisib

产品编号 T2235 CAS 915019-65-7

别名: 2-甲基-2-[4-[3-甲基-2-氧代-8-(喹啉-3-基)-2,3-二氢咪唑并[4,5-c]喹啉-1-基]苯基]丙腈, BEZ235, NVP-BEZ235

Dactolisib (BEZ235) 是一种可口服的 pan-class IPI3K 和 mTOR 抑制剂，抑制 mTORC1和 mTORC2，作用于 p110α/γ/δ/β和 mTOR，IC50分别为 4 nM/5 nM/7 nM/75 nM 和 20.7 nM。

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Dactolisib, CAS 915019-65-7

规格	价格/CNY	货期
10 mg	￥ 323	现货
50 mg	￥ 688	现货
100 mg	￥ 996	现货
200 mg	￥ 1,489	现货
500 mg	￥ 2,866	现货

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其他形式的 Dactolisib:

Dactolisib Tosylate
现货

选择批次

纯度: 99.85%

纯度: 99.71%

纯度: 98.38%

纯度: 97.64%

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生物活性

化学信息

存储 & 溶解度

参考文献

相关产品

产品描述	Dactolisib (BEZ235) is an orally bioavailable inhibitor of PI3K and mTOR (IC50s: 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR).
靶点活性	p110α:4 nM (cell free), p110γ:5 nM (cell free), mTOR (p70S6K):6 nM (cell free), p110δ:7 nM (cell free), p110β:75 nM (cell free)
体外活性	Dactolisib (BEZ235) shows slightly lower activity against the β paralogue (IC50: 75 nmol/L). NVP-BEZ235 (250 nmol/L) was able to reduce IGF-I-induced S473P-Akt levels below the limit of detection, whereas the phosphorylation of the p85 binding site on IGF-IR (Y1316) was not altered [1]. BEZ235 provoked a more profound effect with an IC50 value of 1.8 nmol/L and cytostasis was obtained at 10 nmol/L. Moreover, at a concentration of 100 nmol/L, the BrdUrd uptake was less than the one observed in starved, VEGF-untreated cells, indicative of cell death induction [2].
体内活性	In the absence of inhibitors, the weight of the chamber, as well as levels of the endothelial cell marker Tie-2, were significantly increased in the presence of VEGF. Both effects were significantly inhibited in a dose-dependent manner when the mice were treated with NVP-BEZ235 given p.o. twice a day at 20 mg/kg or once at 30 mg/kg, showing the specificity of the angiogenic response driven by the VEGF [2]. NVP-BEZ235–treated adenomas (20 mg/kg) showed pronounced vacuolation of the cytoplasm when compared with PEG-treated animals. Vacuoles appeared even more prominent at the 30 and 45 mg/kg doses [3].
激酶实验	PI3Kα, β, and δ proteins were composed of the iSH2 domain of p85 NH2-terminally fused to the full-length protein p110 protein, with the exception of α that also did not contain the last 20 amino acids. PI3Kγ was produced as full-length protein deleted for its first 144 amino acids. All constructs were fused to a COOH-terminal His tag for convenient purification and then cloned into the pBlue-Bac4.5 (for α, β, and δ isoforms) or pVL1393 (for γ isoform) plasmids. The different vectors were then cotransfected with BaculoGold WT genomic DNA using methods recommended by the vendor for production of the respective recombinant baculoviruses and proteins. Compounds were tested for their activity against PI3K using a Kinase-Glo assay. The kinase reaction was done in 384-well black plate. Each well was loaded with 50 nL of test items (in 90% DMSO) and 5 μL reaction buffer [10 mmol/L Tris-HCl (pH 7.5), 50 mmol/L NaCl, 3 mmol/L MgCl2, 1 mmol/L DTT, and 0.05% CHAPS] containing 10 μg/mL PI substrate (l-α-phosphatidylinositol; Avanti Polar Lipids; prepared in 3% octyl-glucoside) and the PI3K proteins (10, 25, 10, and 150 nmol/L of p110α, p110β, p110δ, and p110γ, respectively) were then added. The reaction was started by the addition of 5 μL of 1 μmol/L ATP prepared in the reaction buffer and ran for either 60 (for p110α, p110β, and p110δ) or 120 min (for p110γ) and subsequently terminated by the addition of 10 μL Kinase-Glo buffer. The plates were then read in a Synergy 2 reader for luminescence detection [1].
细胞实验	The proliferation of BON1, QGP1, and αT3 cells after treatment was measured with the WST-1 colorimetric assay. Cell proliferation in 3D spheroids was measured with the CellTiter-Glo Cell Viability Assay according to the manufacturer's recommendations. Apoptosis was measured by assessing the activity of caspase-3/7 using the Caspase-Glo 3/7 Assay Kit. BON1 cells and QGP1 cells were transfected with scrambled or anti-DEFB1 siRNA as above, and 24 hours later treated with NVP-BEZ235 or DMSO for an additional 24 hours. Caspase-3/7 activity was then assessed with a proluminescent caspase-3/7 substrate, which contains the tetrapeptide sequence DEVD. Luminescence was measured with a luminometer [3].
动物实验	Three doses of NVP-BEZ235 were tested in MENX rats: 20, 30, and 45 mg/kg. As the two higher doses caused a weight loss >10% after 10 days of treatment, the dose of 20 mg/kg was used for further studies. For MRI studies, MENX-affected rats at 7 to 8 months of age (with sizeable adenomas but still in good general health) were treated for 14 days with NVP-BEZ235 (20 mg/kg) or placebo (PEG) administered daily per oral gavage. The side effect of the drug we observed was mild diarrhea in the last days of the treatment (4/8 rats). Being this our first in vivo study of spontaneous rat pituitary adenomas, functional/molecular changes in the tumors were considered more objective and measurable endpoints (primary endpoints) compared to the size and/or survival (secondary endpoints) [3].

别名	2-甲基-2-[4-[3-甲基-2-氧代-8-(喹啉-3-基)-2,3-二氢咪唑并[4,5-c]喹啉-1-基]苯基]丙腈, BEZ235, NVP-BEZ235
分子量	469.54
分子式	C30H23N5O
CAS No.	915019-65-7

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

DMSO: 5.2 mg/mL (11.07 mM), Sonication and heating are recommended.

H2O: < 0.1 mg/mL (insoluble)

溶液配制表

可选溶剂	浓度体积质量	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.1297 mL	10.6487 mL	21.2974 mL	53.2436 mL
	5 mM	0.4259 mL	2.1297 mL	4.2595 mL	10.6487 mL
	10 mM	0.213 mL	1.0649 mL	2.1297 mL	5.3244 mL

计算器

摩尔浓度计算器

稀释计算器

配液计算器

分子量计算器

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参考文献

1. Maira SM, 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 Jul;7(7):1851-63. 2. Schnell CR, 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 Aug 15;68(16):6598-607. 3. Lee M, et al. Targeting PI3K/mTOR Signaling Displays Potent Antitumor Efficacy against Nonfunctioning Pituitary Adenomas. Clin Cancer Res. 2015 Jul 15;21(14):3204-15.

文献引用

1. Meng Y, Lv T, Zhang J, et al.Temporospatial inhibition of Erk signaling is required for lymphatic valve formation.Signal Transduction and Targeted Therapy.2023, 8(1): 342. 2. Yang N, Fan Z, Sun S, et al.Discovery of highly potent and selective KRASG12C degraders by VHL-recruiting PROTACs for the treatment of tumors with KRASG12C-Mutation.European Journal of Medicinal Chemistry.2023: 115857.

剂量换算

对于不同动物的给药剂量换算，您也可以参考 更多...

体内实验配液计算器

请在以下方框中输入您的动物实验信息后点击计算，可以得到母液配置方法和体内配方的制备方法：比如您的给药剂量是10 mg/kg，每只动物体重20 g，给药体积100 μL，一共给药动物10 只，您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。

母液配置方法：2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL)，如您需要配置的浓度超过该产品的溶解度，请先与我们联系。

体内配方的制备方法：取 50 μL DMSO 主液，加入 300 μL PEG300，混匀澄清，再加 50 μL Tween 80，混匀澄清，再加 600 μL ddH2O, 混匀澄清。

第一步：请输入动物实验的基本信息

剂量

mg/kg

每只动物体重

g

给药体积

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动物数量

第二步：请输入动物体内配方组成，不同的产品配方组成不同，如有配方需求，可先联系我们提供正确的体内配方。

% DMSO+

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% Tween 80+

% ddH₂O

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计算重置

计算结果如下:

工作液浓度: mg/ml;

母液配置方法: mg 药物溶于 μL DMSO (母液浓度为 mg/mL)，如您需要配置的浓度超过该产品的溶解度，请先与我们联系。

体内配方的制备方法：取 μL DMSO 主液，加入 μL PEG300，混匀澄清，再加 μL Tween 80，混匀澄清，再加 μL ddH₂O, 混匀澄清。

备注:

要按顺序从左向右依次添加助溶剂。可配合物理方法，如涡流、超声波或热水浴使之帮助溶解。

技术支持

您可能有的问题的答案可以在抑制剂处理说明中找到，包括如何准备库存溶液，如何存储产品，以及基于细胞的分析和动物实验需要特别注意的问题。

Keywords

Dactolisib 915019-65-7 Autophagy DNA Damage/DNA Repair PI3K/Akt/mTOR signaling ATM/ATR PI3K mTOR inhibit Phosphoinositide 3-kinase BEZ-235 2-甲基-2-[4-[3-甲基-2-氧代-8-(喹啉-3-基)-2,3-二氢咪唑并[4,5-c]喹啉-1-基]苯基]丙腈 Mammalian target of Rapamycin NVP-BEZ-235 Inhibitor BEZ 235 BEZ235 NVP-BEZ235 NVP-BEZ 235 inhibitor

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Dactolisib

存储

溶解度

溶液配制表

计算器

输入分子式，点击计算，可计算出产品的分子量。

参考文献

文献引用

相关产品

相关化合物库

剂量换算

体内实验配液计算器

技术支持

Keywords