1. Cell Cycle/DNA Damage
  2. Polo-like Kinase (PLK)
  3. GSK461364

GSK461364  (Synonyms: GSK461364A)

目录号: HY-50877 纯度: 99.20%
COA 产品使用指南

GSK461364 是选择性,可逆,ATP竞争性的 PLK1 抑制剂,Ki 值为 2.2 nM。

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GSK461364 Chemical Structure

GSK461364 Chemical Structure

CAS No. : 929095-18-1

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规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥957
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1 mg ¥335
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5 mg ¥800
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10 mg ¥1500
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50 mg ¥4800
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100 mg ¥7200
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500 mg   询价  

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Top Publications Citing Use of Products

    GSK461364 purchased from MCE. Usage Cited in: Eur J Cancer. 2013 Sep;49(14):3020-8.  [Abstract]

    Western blot analysis of PLK1 protein levels from GSK461364A treated U251 cells; actin levels are measured as a loading control.

    查看 Polo-like Kinase (PLK) 亚型特异性产品:

    • 生物活性

    • 实验参考方法

    • 纯度 & 产品资料

    • 参考文献

    生物活性

    GSK461364 is a selective, reversible and ATP-competitive Polo-like kinase 1 (PLK1) inhibitor with a Ki value of 2.2 nM.

    IC50 & Target[3]

    PLK1

    2.2 nM (Ki)

    体外研究
    (In Vitro)

    GSK461364 is a potent, selective, and reversible ATP-competitive Plk1 inhibitor (Ki, 2.2 nM) with at least 390-fold greater selectivity for Plk1 than for Plk2 and Plk3 and 1,000-fold greater selectivity than for a panel of 48 other kinases[1]. GSK461364 (GSK461364A, 250 nM) inhibiting plk1 causes prolonged mitotic delay, aberrant mitotic exit, and p53 activation in A549 and PL45 cells. Knockdown of p53 significantly enhances the sensitivity of the cells to GSK461364A (30 or 300 nM) in preventing outgrowth in A549 and NCI-H460 cells, compared with cells with nonsilencing control siRNA[2]. GSK461364 can inhibits cell growth of most proliferating cancer cell lines, and suppresses 89% of cancer cell line (66 of 74 lines) proliferation, with a GI50 (concentration required to inhibit 50% cell growth) of ≤100 nM. GSK461364 (GSK461364A, >20 nM) blocks cells in G2-M phase with reduction of cells in G1 phase of A549 lung carcinoma line. GSK461364 (10-250 nM) blocks cells in G2 and M phases of the cell cycle and causes M-phase caspase-3/caspase-7 activation in cancer cells[3]. GSK461364 (0.5-2 μM) decreases level of PLK1 and pCDC25C, and cuases a dose- and time-dependent increase in pHisH3, an indicator of mitotic arrest in OS cell lines[4].

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

    体内研究
    (In Vivo)

    GSK461364 (50 mg/kg) exhibits various degrees of tumor growth delay (TGD) in multiple xenograft tumor models by i.p. one dose every 2 days repeated twelve times (q2d×12)[1].

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

    Clinical Trial
    分子量

    543.60

    Formula

    C27H28F3N5O2S

    CAS 号
    性状

    固体

    颜色

    White to gray

    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: 

    DMSO 中的溶解度 : 50 mg/mL (91.98 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响,请使用新开封的 DMSO)

    配制储备液
    浓度 溶剂体积 质量 1 mg 5 mg 10 mg
    1 mM 1.8396 mL 9.1979 mL 18.3959 mL
    5 mM 0.3679 mL 1.8396 mL 3.6792 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: ≥ 2.5 mg/mL (4.60 mM); 澄清溶液

      此方案可获得 ≥ 2.5 mg/mL(饱和度未知)的澄清溶液。

      1 mL 工作液为例,取 100 μL 25.0 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% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.5 mg/mL (4.60 mM); 澄清溶液

      此方案可获得 ≥ 2.5 mg/mL(饱和度未知)的澄清溶液。

      1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中,混合均匀。

      20% SBE-β-CD in Saline 的配制(4°C,储存一周):2 g SBE-β-CD(磺丁基醚 β-环糊精)粉末定容于 10 mL 的生理盐水中,完全溶解至澄清透明。
    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: 99.82%

    参考文献
    Kinase Assay
    [3]

    Kinase reactions are performed in a final assay volume of 10 μL using the Z'-Lyte Assay kit (Ser/Thr peptide 16). Briefly, reactions contained 50 mM HEPES (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 1 mM DTT, 0.01% Brij 35, 0.01 mg/mL casein, 200 μM ATP, 200 μM Polo Box peptide (NH2-MAGPMQS[pT]PLNGAKK-OH), and 6 nM recombinant Plk1 (H6-tev-PLK 1-603). Plk1 is preincubated for 60 min in the presence or absence of 0 to 1,000 nM GSK461364. Reactions are then initiated by the addition of 2 μM peptide. After 15 min at 23°C, reactions are quenched and processed according the Z'-Lyte protocol and read on an plate reader. Raw fluorescence values are converted to concentration of product formed using substrate and product standards. IC50 values are determined using a two-parameter fit (Hill coefficient and IC50) using GraFit software. Because the potency of inhibition for GSK461364 is observed to vary as a function of the ATP concentration in a manner consistent with an ATP-competitive mode of inhibition, an upper limit for the Ki*app for GSK461364 is determined by applying the Cheng-Prusoff relationship for a competitive inhibitor (ATP Km*app=16 μM) to the IC50 value obtained with 60 min preincubation of GSK461364.

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

    Cell Assay
    [3]

    Cell lines grow in the recommended media at 37°C, 5% CO2 in a humidified incubator. Cells are plated in triplicate 96-well microtiter plates at 1,000 cells per well in culture media. GSK461364 (GSK461364A) dissolved in DMSO or negative control (0.1% DMSO) are added the following day, and one plate is harvested with 50 μL of CellTiter-Glo for a time 0 (T=0) measurement.

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

    Animal Administration
    [3]

    Cells are implanted in Nude mice and grown as tumor xenografts. Dosing began when tumors achieve appr 100 mm3. GSK461364 (GSK461364A) or the vehicle [4% DMA/Cremaphore (50:50), pH 5.6] is given i.p. to mice every 2 d (q2d×6, q2d×12) or every 4 d (q4d×3) at nominal dose levels of 25, 50, and 100 mg/kg/dose. Results are reported as median tumor volume for n=7 to 8 mice. Paclitaxel (30 mg/kg i.v.; q4d×3) is used as a positive control for comparison. Tumors are measured thrice a week with Vernier calipers, and tumor volume is calculated from two-dimensional measurements using an equation approximating the volume of a prolate ellipsoid [tumor volume mm3=(length × width2) × 0.5]. The maximum tolerated dose is defined as the highest dose that produces >20% mortality or >20% weight loss (appr 4 g). Antitumor activity is defined as tumor growth delay (TGD), partial regression (PR), or complete regression (CR). TGD represents the time differential between the treated and control tumors to reach a predetermined tumor volume of 1,000 mm3. PR is defined as a decrease in an individual tumor volume to one-half the initial starting volume for at least 1 wk (three consecutive measurements). CR is defined as a decrease in an individual tumor volume to <13 mm3 for at least 1 wk.

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

    参考文献

    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
    DMSO 1 mM 1.8396 mL 9.1979 mL 18.3959 mL 45.9897 mL
    5 mM 0.3679 mL 1.8396 mL 3.6792 mL 9.1979 mL
    10 mM 0.1840 mL 0.9198 mL 1.8396 mL 4.5990 mL
    15 mM 0.1226 mL 0.6132 mL 1.2264 mL 3.0660 mL
    20 mM 0.0920 mL 0.4599 mL 0.9198 mL 2.2995 mL
    25 mM 0.0736 mL 0.3679 mL 0.7358 mL 1.8396 mL
    30 mM 0.0613 mL 0.3066 mL 0.6132 mL 1.5330 mL
    40 mM 0.0460 mL 0.2299 mL 0.4599 mL 1.1497 mL
    50 mM 0.0368 mL 0.1840 mL 0.3679 mL 0.9198 mL
    60 mM 0.0307 mL 0.1533 mL 0.3066 mL 0.7665 mL
    80 mM 0.0230 mL 0.1150 mL 0.2299 mL 0.5749 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.

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    产品名称:
    GSK461364
    目录号:
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