1. PI3K/Akt/mTOR Autophagy
  2. PI3K mTOR Autophagy
  3. Dactolisib

Dactolisib  (Synonyms: BEZ235; NVP-BEZ235)

目录号: HY-50673 纯度: 99.94%
COA 产品使用指南

Dactolisib (BEZ235) 是一种具有口服活性的、双重的 pan-class I PI3KmTOR 抑制剂,作用于 p110α/γ/δ/βmTORIC50 分别为 4 nM/5 nM/7 nM/75 nM 和 20.7 nM。Dactolisib (BEZ235) 抑制 mTORC1mTORC2

MCE 的所有产品仅用作科学研究或药证申报,我们不为任何个人用途提供产品和服务

我们将采用定制合成服务的方式为您快速提供所需产品和技术服务

Dactolisib Chemical Structure

Dactolisib Chemical Structure

CAS No. : 915019-65-7

1.  客户无需承担相应的运输费用。

2.  同一机构(单位)同一产品试用装仅限申领一次,同一机构(单位)一年内

     可免费申领三个不同产品的试用装。

3.  试用装只面向终端客户

规格 价格 是否有货 数量
1 mg ¥121
In-stock
5 mg ¥243
In-stock
10 mg ¥390
In-stock
50 mg ¥810
In-stock
100 mg ¥1252
In-stock
200 mg ¥1800
In-stock
500 mg ¥3500
In-stock
1 g   询价  
5 g   询价  

* Please select Quantity before adding items.

Customer Review

Other Forms of Dactolisib:

注册 MCE会员完成审核
即刻享有 积分商城 300 专属积分

Top Publications Citing Use of Products

MCE 顾客使用本产品发表的 50 篇科研文献

WB

    Dactolisib purchased from MCE. Usage Cited in: J Exp Clin Cancer Res. 2018 Aug 9;37(1):188.  [Abstract]

    Representative images of the western blotting analysis of TSSC3, ATG5, P62, LC3, Src, Akt, mTOR and their phosphorylated versions in MTF and SaOS2 cells. Cells are treated with TSSC3-overexpression, IGF-1, p-YEEI, and BEZ235 separately or in combination.

    Dactolisib purchased from MCE. Usage Cited in: Biomed Res Int. 2018 Aug 5;2018:8372085.  [Abstract]

    Changes of p-AKT and p-p70 S6K proteins after treatment with NVP-BEZ235 in Ishikawa and Ishikawa-TAX cells. Changes of p-AKT and p-p70 S6K proteins after treatment of Ishikawa and Ishikawa-TAX cells with NVP-BEZ235.

    Dactolisib purchased from MCE. Usage Cited in: Nat Commun. 2017 Jun 8;8:15617.  [Abstract]

    Immunoblot analysis of KRAS protein levels in parental (P) and resistant derivatives (R1 and R2) following 4 h treatment with the corresponding inhibitors Rapamycin, AZD2014, MLN0128, BEZ235 and 4EGI-1. Images are cropped for clarity from the same exposure of the same membrane.

    Dactolisib purchased from MCE. Usage Cited in: Oncotarget. 2017 Jul 11;8(28):45470-45483.  [Abstract]

    Activity of PI3K/AKT/mTOR is monitored by examining phosphorylation of AKT-S473, AKT-T308, and S6 by western blotting.

    Dactolisib purchased from MCE. Usage Cited in: Leukemia. 2014 Sep;28(9):1819-27.  [Abstract]

    Western blot analysis of human T-ALL cell lines treated for 24 hours using DMSO (vehicle control), 1 μM JQ1, 500 nM BEZ235, or both drugs in combination, using the indicated antibodies. Western blot analysis of these T-ALL cell lines following treatment with JQ1, BEZ235 or both drugs in combination reveals cooperative upregulation of BIM protein expression coupled to induction of apoptosis, as assessed by PARP cleavage.
    • 生物活性

    • 实验参考方法

    • 纯度 & 产品资料

    • 参考文献

    生物活性

    Dactolisib (BEZ235) is an orally active and dual pan-class I PI3K and mTOR kinase inhibitor with IC50s of 4 nM/5 nM/7 nM/75 nM, and 20.7 nM for p110α/p110γ/p110δ/p110β and mTOR, respectively. Dactolisib (BEZ235) inhibits both mTORC1 and mTORC2.

    IC50 & Target[1]

    p110α

    4 nM (IC50)

    p110α-H1047R

    4.6 nM (IC50)

    p110α-E545K

    5.7 nM (IC50)

    p110γ

    5 nM (IC50)

    p110δ

    7 nM (IC50)

    p110β

    75 nM (IC50)

    mTOR

    20.7 nM (IC50)

    mTORC1

     

    mTORC2

     

    Autophagy

     

    体外研究
    (In Vitro)

    Dactolisib (BEZ235) potently inhibits PI3K in an ATP Competitive Manner. Dactolisib (BEZ235) (250 nM) significantly reduced the phosphorylation levels of the mTOR activated kinase p70S6K. Dactolisib (BEZ235) also leads to a reduction of S235/S236P-RPS6 levels with an IC50 of 6.5 nM, suggesting that Dactolisib (BEZ235) can directly inhibit the mTOR kinase, as the kinase domain of mTOR is highly homologous to the one of class IA PI3K. The activity of Dactolisib (BEZ235) against mTOR is confirmed using a biochemical mTOR K-LISA assay (IC50, 20.7 nM)[1].
    The IC50s of Dactolisib (BEZ235) for HCT116, DLD-1, and SW480 cell lines are 14.3±6.4, 9.0±1.5, and 12.0±1.6 nM, respectively[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    体内研究
    (In Vivo)

    Dactolisib (BEZ235) (45 mg/kg, p.o.) treatment induces colonic tumor regression in a GEM model for sporadic PIK3CA wild-type CRC[2]. Dactolisib (BEZ235) (45 mg/kg) is administered to MENX rats (n=2 each group) by oral gavage and animals are sacrificed 1 or 6 hours after treatment. Immunostains for P-AKT and P-S6 show considerable reduction of the two proteins, and particularly of P-S6, 6 hours after administration of Dactolisib (BEZ235) when compares with PEG-treated rats. At 6 hours after treatment, the pituitary adenomas of Dactolisib (BEZ235)-treated rats has a proteomic profile significantly different from the tumors of placebo-treated rats[3].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Clinical Trial
    分子量

    469.54

    Formula

    C30H23N5O

    CAS 号
    性状

    固体

    颜色

    White to light yellow

    运输条件

    Room temperature in continental US; may vary elsewhere.

    储存方式
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    溶解性数据
    In Vitro: 

    5% TFA 中的溶解度 : 8.33 mg/mL (17.74 mM; 超声助溶 (<60°C))

    DMSO 中的溶解度 : 7.81 mg/mL (16.63 mM; 超声助溶 (<60°C); 吸湿的 DMSO 对产品的溶解度有显著影响,请使用新开封的 DMSO)

    DMF 中的溶解度 : 2 mg/mL (4.26 mM; 超声助溶)

    配制储备液
    浓度 溶剂体积 质量 1 mg 5 mg 10 mg
    1 mM 2.1297 mL 10.6487 mL 21.2974 mL
    5 mM 0.4259 mL 2.1297 mL 4.2595 mL
    查看完整储备液配制表

    * 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, 2 years; -20°C, 1 year。-80°C储存时,请在2年内使用, -20°C储存时,请在1年内使用。

    • 摩尔计算器

    • 稀释计算器

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    质量
    =
    浓度
    ×
    体积
    ×
    分子量 *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    浓度 (start)

    C1

    ×
    体积 (start)

    V1

    =
    浓度 (final)

    C2

    ×
    体积 (final)

    V2

    In Vivo:

    请根据您的 实验动物和给药方式 选择适当的溶解方案。

    以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:
    ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用
    以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

    • 方案 一

      请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 0.52 mg/mL (1.11 mM); 澄清溶液

      此方案可获得 ≥ 0.52 mg/mL(饱和度未知)的澄清溶液。

      1 mL 工作液为例,取 100 μL 5.2 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;再向上述体系中加入 50 μL Tween-80,混合均匀;然后再继续加入 450 μL 生理盐水 定容至 1 mL

      生理盐水的配制:将 0.9 g 氯化钠,溶解于 ddH₂O 并定容至 100 mL,可以得到澄清透明的生理盐水溶液。
    • 方案 二

      请依序添加每种溶剂: 10% DMSO    90% Corn Oil

      Solubility: ≥ 0.52 mg/mL (1.11 mM); 澄清溶液

      此方案可获得 ≥ 0.52 mg/mL(饱和度未知)的澄清溶液,此方案实验周期在半个月以上的动物实验酌情使用。

      1 mL 工作液为例,取 100 μL 5.2 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

    以下溶解方案,请直接配置工作液。建议现用现配,在短期内尽快用完。 以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比; 如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶。

    • 方案 一

      请依序添加每种溶剂: 50% PEG300    50% Saline

      Solubility: 12.5 mg/mL (26.62 mM); 悬浊液; 超声助溶

    • 方案 二

      请依序添加每种溶剂: 10% 1-Methyl-2-pyrrolidinone    90% PEG300

      Solubility: ≥ 1.1 mg/mL (2.34 mM); 澄清溶液

    动物溶解方案计算器
    请输入动物实验的基本信息:

    给药剂量

    mg/kg

    动物的平均体重

    g

    每只动物的给药体积

    μL

    动物数量

    由于实验过程有损耗,建议您多配一只动物的量
    请输入您的动物体内配方组成:
    %
    DMSO +
    +
    %
    Tween-80 +
    %
    Saline
    如果您的动物是免疫缺陷鼠或者体弱鼠,建议 DMSO 中的在最后工作液体系中的占比尽量不超过 2%。
    方案所需 助溶剂 包括:DMSO ,均可在 MCE 网站选购。 Tween 80,均可在 MCE 网站选购。
    计算结果
    工作液所需浓度 : mg/mL
    储备液配制方法 : mg 药物溶于 μL  DMSO(母液浓度为 mg/mL)。
    您所需的储备液浓度超过该产品的实测溶解度,以下方案仅供参考,如有需要,请与 MCE 中国技术支持联系。
    动物实验体内工作液的配制方法 : 取 μL DMSO 储备液,加入 μL  μL ,混合均匀至澄清,再加 μL Tween 80,混合均匀至澄清,再加 μL 生理盐水
    连续给药周期超过半月以上,请谨慎选择该方案。
    请确保第一步储备液溶解至澄清状态,从左到右依次添加助溶剂。您可采用超声加热 (超声清洗仪,建议频次 20-40 kHz),涡旋吹打等方式辅助溶解。
    纯度 & 产品资料

    纯度: 99.94%

    参考文献
    Cell Assay
    [2]

    HCT116 (PIK3CA mutant; kinase domain at H1047R), DLD-1 (PIK3CA mutant; helical domain at E545K), and SW480 (PIK3CA wild-type) human CRC cell lines (ATCC) and isogenic DLD-1 PIK3CA mutant and wild-type cells are maintained in DMEM. Cells are plated at different initial densities (HCT116: 3,000 cells/well, DLD-1: 5,500 cells/well, SW480: 4,500 cells/well, DLD-1 PIK3CA mutant: 7,000 cells/well, and DLD-1 PIK3CA wild-type: 9,000 cells/well) to account for differential growth kinetics. After 16 hours, cells are incubated with increasing concentrations of BEZ235 (10, 100, 1000 nM), and drug-containing growth medium is changed every 24 hours. Cell viability is assessed 16 hours after the initial plating and 48 hours after initiation of drug treatment using the colorimetric MTS assay CellTiter 96 AQueous One Solution Cell Proliferation Assay. Cell viability after drug treatment is normalized to that of untreated cells also grown for 48 hours. IC50 values are calculated using 4 parameter nonlinear regression in GraphPad Prism 5[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2][3]

    Mice[2]
    Tumor-bearing Apc CKO mice are randomly assigned to treatment with either control vehicle alone (n=8) or 45 mg/kg body weight BEZ235 in 10% 1-methyl-2-pyrrolidone/90% PEG 300 (n=8) by daily oral gavage for 28 days. The treatment dose is chosen based on literature indicating that 40-50 mg/kg body weight BEZ235 effectively treats murine tumor models without adverse effects. Base on pharmacokinetic studies demonstrating maximal tissue concentration one hour after NVP-BEZ235 administration, tumor-bearing mice are sacrificed one hour after final treatment dose. Colonic tumor volume is assessed using calipers (width×length×height) and tumors are harvested for both western blot analysis and immunohistochemistry.
    Rats[3]
    MENX-affected rats used. Three doses of BEZ235 are tested in MENX rats: 20, 30, and 45 mg/kg. As the two higher doses causes a weight loss >10% after 10 days of treatment, the dose of 20 mg/kg is 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) are treated for 14 days with BEZ235 (20 mg/kg) or placebo (PEG) administered daily per oral gavage.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    参考文献

    Dactolisib 相关分类

    完整储备液配制表

    * 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, 2 years; -20°C, 1 year。-80°C储存时,请在2年内使用, -20°C储存时,请在1年内使用。

    可选溶剂 浓度 溶剂体积 质量 1 mg 5 mg 10 mg 25 mg
    DMF / DMSO / 5% TFA 1 mM 2.1297 mL 10.6487 mL 21.2974 mL 53.2436 mL
    DMSO / 5% TFA 5 mM 0.4259 mL 2.1297 mL 4.2595 mL 10.6487 mL
    10 mM 0.2130 mL 1.0649 mL 2.1297 mL 5.3244 mL
    15 mM 0.1420 mL 0.7099 mL 1.4198 mL 3.5496 mL
    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    您最近查看的产品:

    Your information is safe with us. * Required Fields.

       产品名称:

     

    * 需求量:

    * 客户姓名:

     

    * Email:

    * 电话:

     

    * 公司或机构名称:

       留言给我们:

    Bulk Inquiry

    Inquiry Information

    产品名称:
    Dactolisib
    目录号:
    HY-50673
    需求量: