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  2. Apoptosis
  3. RIP kinase
  4. GSK583

GSK583 是一種高效、口服有效的、高選擇性的 RIP2 Kinase 抑制劑，其 IC50 值為 5 nM。GSK583 可同時抑制TNF-α 和IL-6 的產(chǎn)生，IC50 值為 200 nM。

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GSK583 Chemical Structure

GSK583 Chemical Structure

CAS No. : 1346547-00-9

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規(guī)格 價格 是否有貨 數(shù)量
10 mM * 1 mL in DMSO ￥1227
In-stock
1 mg ￥534
In-stock
2 mg ￥750
In-stock
5 mg ￥1400
In-stock
10 mg ￥1960
In-stock
25 mg ￥3435
In-stock
50 mg ￥5153
In-stock
100 mg 現(xiàn)貨 詢價
500 mg 現(xiàn)貨 詢價
1 g   詢價  
5 g   詢價  

* Please select Quantity before adding items.

Customer Review

    GSK583 purchased from MCE. Usage Cited in: J Immunol. 2017 May 1;198(9):3729-3736.  [Abstract]

    Confocal images of lysozyme and procryptdin in cultured WT crypt organoids treated with GSK583 (5 μM) or mock-treated (A), or WEHI-345 (2.5 μM) or mock-treated (B) for 16 hours.

    查看 RIP kinase 亞型特異性產(chǎn)品:

    • 生物活性

    • 實驗參考方法

    • 純度 & 產(chǎn)品資料

    • 參考文獻(xiàn)

    生物活性

    GSK583 is a highly potent, orally active and selective inhibitor of RIP2 Kinase, with IC50 of 5 nM. GSK583 inhibits both TNF-α and IL-6 production with an IC50 value of 200 nM.

    IC50 & Target

    IC50: 5 nM (RIP2K)[1]
    細(xì)胞效力
    (Cellular Effect)
    Cell Line Type Value Description References
    Monocyte IC50
    8 nM
    Compound: 27
    Inhibition of MDP-stimulated TNF-alpha release in human monocytes preincubated for 30 mins prior to MDP stimulation measured after 6 hrs by immunoassay
    Inhibition of MDP-stimulated TNF-alpha release in human monocytes preincubated for 30 mins prior to MDP stimulation measured after 6 hrs by immunoassay
    		[PMID: 27109867]
    體外研究
    (In Vitro)

    GSK583 (1 μM) 在 300 種激酶 (包括 p38α 和 VEGFR2) 中表現(xiàn)出良好的選擇性。GSK583 有效且劑量依賴地抑制 MDP 刺激的腫瘤壞死因子 α (TNFα) 的產(chǎn)生，IC50 為 8 nM。在類似的 MDP 誘導(dǎo)的人全血 (IC50=237 nM) 和大鼠全血 (IC50=133 nM) 中，GSK583 僅 顯示出適度的降低效力[1]。

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    體內(nèi)研究
    (In Vivo)

    GSK583 (0.1、1 和 10 mg/kg，口服) 以劑量依賴性方式抑制大鼠血清 KC (IL-8 的嚙齒動物直系同源物) 水平，IC50 濃度為 50 nM (或 20 ng/mL) (來自大鼠血液)。同樣，GSK583 以劑量依賴性方式抑制小鼠血清 KC 水平和中性粒細(xì)胞向腹膜腔募集，IC50 為 37 nM (15 ng/mL)，源自小鼠血液[1]。

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

    398.45

    Formula

    C20H19FN4O2S
    CAS 號
    性狀

    固體

    顏色

    Light yellow to yellow

    運輸條件

    Room temperature in continental US; may vary elsewhere.
    儲存方式
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 1 year
    -20°C 6 months
    溶解性數(shù)據(jù)
    細(xì)胞實驗： 

    DMSO 中的溶解度 : ≥ 100 mg/mL (250.97 mM; 吸濕的 DMSO 對產(chǎn)品的溶解度有顯著影響，請使用新開封的 DMSO)

    * "≥" means soluble, but saturation unknown.

    配制儲備液
    濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg
    1 mM 2.5097 mL 12.5486 mL 25.0972 mL
    5 mM 0.5019 mL 2.5097 mL 5.0195 mL
    查看完整儲備液配制表

    * 請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
    儲備液的保存方式和期限：-80°C, 1 year; -20°C, 6 months。-80°C儲存時，請在1年內(nèi)使用， -20°C儲存時，請在6個月內(nèi)使用。

    • 摩爾計算器

    • 稀釋計算器

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

    質(zhì)量
    =
    濃度
    ×
    體積
    ×
    分子量 *

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    濃度 (start)

    C1

    ×
    體積 (start)

    V1

    =
    濃度 (final)

    C2

    ×
    體積 (final)

    V2

    動物實驗：

    請根據(jù)您的 實驗動物和給藥方式 選擇適當(dāng)?shù)娜芙夥桨浮?

    以下溶解方案都請先按照 In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：
    ——為保證實驗結(jié)果的可靠性，澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的工作液，建議您現(xiàn)用現(xiàn)配，當(dāng)天使用；
    以下溶劑前顯示的百分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶

    • 方案 一

      請依序添加每種溶劑： 10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (6.27 mM); 澄清溶液

      此方案可獲得 ≥ 2.5 mg/mL（飽和度未知）的澄清溶液。

      以 1 mL 工作液為例，取 100 μL 25.0 mg/mL 的澄清 DMSO 儲備液加到 400 μL PEG300 中，混合均勻；再向上述體系中加入 50 μL Tween-80，混合均勻；然后再繼續(xù)加入 450 μL 生理鹽水 定容至 1 mL。

      生理鹽水的配制：將 0.9 g 氯化鈉，溶解于 ddH?O 并定容至 100 mL，可以得到澄清透明的生理鹽水溶液。
    • 方案 二

      請依序添加每種溶劑： 10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.5 mg/mL (6.27 mM); 澄清溶液

      此方案可獲得 ≥ 2.5 mg/mL（飽和度未知）的澄清溶液。

      以 1 mL 工作液為例，取 100 μL 25.0 mg/mL 的澄清 DMSO 儲備液加到 900 μL 20% 的 SBE-β-CD 生理鹽水水溶液 中，混合均勻。

      2 g SBE-β-CD（磺丁基醚 β-環(huán)糊精）粉末定容于 10 mL 的生理鹽水中，完全溶解至澄清透明。
    動物溶解方案計算器
    請輸入動物實驗的基本信息：

    給藥劑量

    mg/kg

    動物的平均體重

    g

    每只動物的給藥體積

    μL

    動物數(shù)量

    只
    由于實驗過程有損耗，建議您多配一只動物的量
    請輸入您的動物體內(nèi)配方組成：
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    如果您的動物是免疫缺陷鼠或者體弱鼠，建議 DMSO 中的在最后工作液體系中的占比盡量不超過 2%。
    方案所需 助溶劑 包括：DMSO， ，均可在 MCE 網(wǎng)站選購。 ，Tween 80，均可在 MCE 網(wǎng)站選購。
    計算結(jié)果
    工作液所需濃度 : mg/mL
    儲備液配制方法 : mg 藥物溶于 μL  DMSO（母液濃度為 mg/mL）。
    您所需的儲備液濃度超過該產(chǎn)品的實測溶解度，以下方案僅供參考，如有需要，請與 MCE 中國技術(shù)支持聯(lián)系。
    動物實驗體內(nèi)工作液的配制方法 : 取 μL DMSO 儲備液，加入 μL 。 μL ，混合均勻至澄清，再加 μL Tween 80，混合均勻至澄清，再加 μL 生理鹽水。
    連續(xù)給藥周期超過半月以上，請謹(jǐn)慎選擇該方案。
    請確保第一步儲備液溶解至澄清狀態(tài)，從左到右依次添加助溶劑。您可采用超聲加熱 （超聲清洗儀，建議頻次 20-40 kHz），渦旋吹打等方式輔助溶解。
    純度 & 產(chǎn)品資料

    純度: 99.93%

    參考文獻(xiàn)
    Kinase Assay
    [1]

    A fluorescent polarization based binding assay is developed to quantitate interaction of novel test compounds at the ATP binding pocket of RIP2K by competition with a fluorescently labeled ATP competitive ligand. Full length FLAG His tagged RIP2K is purified from a baculovirus expression system and is used at a final assay concentration of twice the KD apparent. A fluorescent labeled ligand that is reversible and competitive with the inhibitors is used at a final assay concentration of 5 nM. Both the enzyme and ligand are prepared in solutions in 50 mM HEPES pH 7.5, 150 mM NaCl, 10 mM MgCl2, 1 mM DTT, and 1 mM CHAPS. Test compounds are prepared in 100% DMSO, and 100 nL is dispensed to individual wells of a multiwell plate. Next, 5 μL of RIP2K is added to the test compounds at twice the final assay concentration and incubated at room temperature for 10 min. Following the incubation, 5 μL of the fluorescent labeled ligand solution is added to each reaction at twice the final assay concentration and incubated at room temperature for at least 10 min. Finally, samples are read on an instrument capable of measuring fluorescent polarization. Test compound inhibition is expressed as percent (%) inhibition of internal assay controls. For concentration response experiments, normalized data are fit using the following four parameter logistic equation: y = A + ((B-C))/(1+(10x)/(10C)D), where y is the % activity (% inhibition) at a specified compound concentration, A is the minimum % activity, B is the maximum % activity, C = log10(IC50), D = Hill slope, x = log10(compound concentration [M]), and pIC50 = (?C).

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [1]

    Mice[1]
    Female C57Bl/6 mice (for cytokine analyses) or male Balb/c mice (for peritoneal neutrophil analyses) (n=10/treatment group) are dosed orally 15 min prior to MDP challenge with vehicle or GSK583 (0.1, 1, or 10 mg/kg). For peritoneal neutrophil analysis, mice are sacrificed at 4 h post-MDP challenge (30 μg, i.p.) and peritoneal fluid is collected by lavage. Peritoneal neutrophils are quantified by FACS analysis.
    Rats[1]
    Female Crl:CD(SD) rats (n=8/treatment group) are dosed orally with vehicle or GSK583 15 min prior to MDP challenge (150 μg/rat, IV). At 2 h post MDP challenge, rats are sacrificed and terminal serum is prepared from blood collected via cardiac stick. Serum cytokine levels (IL-6, IL-8 or KC, IL-1β, and TNFα) are quantified by the MSD platform.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    參考文獻(xiàn)

    GSK583 相關(guān)分類

    完整儲備液配制表

    * 請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
    儲備液的保存方式和期限：-80°C, 1 year; -20°C, 6 months。-80°C儲存時，請在1年內(nèi)使用， -20°C儲存時，請在6個月內(nèi)使用。

    可選溶劑 濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 2.5097 mL 12.5486 mL 25.0973 mL 62.7431 mL
    5 mM 0.5019 mL 2.5097 mL 5.0195 mL 12.5486 mL
    10 mM 0.2510 mL 1.2549 mL 2.5097 mL 6.2743 mL
    15 mM 0.1673 mL 0.8366 mL 1.6732 mL 4.1829 mL
    20 mM 0.1255 mL 0.6274 mL 1.2549 mL 3.1372 mL
    25 mM 0.1004 mL 0.5019 mL 1.0039 mL 2.5097 mL
    30 mM 0.0837 mL 0.4183 mL 0.8366 mL 2.0914 mL
    40 mM 0.0627 mL 0.3137 mL 0.6274 mL 1.5686 mL
    50 mM 0.0502 mL 0.2510 mL 0.5019 mL 1.2549 mL
    60 mM 0.0418 mL 0.2091 mL 0.4183 mL 1.0457 mL
    80 mM 0.0314 mL 0.1569 mL 0.3137 mL 0.7843 mL
    100 mM 0.0251 mL 0.1255 mL 0.2510 mL 0.6274 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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    產(chǎn)品名稱：
    GSK583
    目錄號：
    HY-100339
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