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  1. PI3K/Akt/mTOR
  2. MELK
  3. MELK-8a hydrochloride

MELK-8a hydrochloride  (Synonyms: NVS-MELK8a hydrochloride)

目錄號: HY-100368A 純度: 99.31%
COA 產(chǎn)品使用指南 技術支持

MELK-8a hydrochloride是一種新穎的母體胚胎亮氨酸拉鏈激酶(MELK)抑制劑,其IC50值為2 nM。

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MELK-8a hydrochloride Chemical Structure

MELK-8a hydrochloride Chemical Structure

CAS No. : 2096992-20-8

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5 mg ¥2800
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Customer Review

Other Forms of MELK-8a hydrochloride:

    MELK-8a hydrochloride purchased from MCE. Usage Cited in: J Biol Chem. 2020 Feb 21;295(8):2359-2374.  [Abstract]

    Asynchronous MDA-MB-468 cells are treated with DMSO or 0.5, 1, or 3 μM 8a for 1, 6, or 24h. Cells are harvested and immunoblotted with the indicated antibodies.

    MELK-8a hydrochloride purchased from MCE. Usage Cited in: J Biol Chem. 2020 Feb 21;295(8):2359-2374.  [Abstract]

    Delayed mitotic entry caused by 8a is associated with delayed activation of Aurora A, Aurora B, and CDK1. HeLaS3 cells are synchronized at G1/S with double thymidine block and released into DMSO or 3 μM 8a. Cells are collected starting at 6h post-release, with subsequent collections completed every 0.5 or 1h, over a 12h timecourse. Cells are lysed and immunoblotted with the indicated antibodies. The split in the image indicates that the samples from DMSO and 3 μM 8a conditions are blotted sepa.

    MELK-8a hydrochloride purchased from MCE. Usage Cited in: J Biol Chem. 2020 Feb 21;295(8):2359-2374.  [Abstract]

    HeLaS3 cells treated with 8a complete mitosis and begin the subsequent cell cycle following delayed mitotic entry. HeLaS3 cells are synchronized at G1/S with double thymidine block and released into DMSO or 3 μM 8a. Cells are collected starting at 6h post-release, with subsequent collections completed every 2h over a 20h timecourse. Cells are lysed and immunoblotted with the indicated antibodies. The split in the image indicates that the samples from DMSO and 3 μM 8a conditions are blotted sepa

    MELK-8a hydrochloride purchased from MCE. Usage Cited in: J Biol Chem. 2020 Feb 21;295(8):2359-2374.  [Abstract]

    MELK inhibition with 3 μM 8a causes delayed mitotic entry. HeLaS3 cells are synchronized at G1/S with double thymidine block and released into DMSO, 1 μM, or 3 μM 8a. Cells are collected every 2h over a 12h timecourse. Cells are lysed and immunoblotted with the indicated antibodies. The splits in the image indicate that the samples from DMSO, 1 μM, and 3 μM 8a conditions are immunoblotted separately due to space constraints. Asynchronous HeLaS3 lysate is loaded in the lanes labeled “A” in order

    MELK-8a hydrochloride purchased from MCE. Usage Cited in: Cell Rep. 2017 Dec 5;21(10):2829-2841.  [Abstract]

    A375 cells are treated with MELK-8a for 48 h and analyzed for indicated proteins by immunoblot analysis. ACTINB is used for as a loading control.
    • 生物活性

    • 實驗參考方法

    • 純度 & 產(chǎn)品資料

    • 參考文獻

    生物活性

    MELK-8a hydrochloride is a novel maternal embryonic leucine zipper kinase (MELK) inhibitor with an IC50 of 2 nM.

    IC50 & Target

    IC50: 2 nM (MELK)[1]

    體外研究
    (In Vitro)

    MELK-8a remains very potent (IC50=140 nM) when the ATP concentration in the biochemical assay is shifted from 20 μM to 2 mM. Its potency is well tracked between full-length MELK versus catalytic domain construct (5 nM versus 2 nM). It only inhibits seven off-target kinases in addition to MELK with >85% inhibition of binding at 1 μM demonstrating great selectivity. The compound is at least 90-fold more selective in targeting MELK in all cases. MELK-8a is fairly soluble (0.22 g/L at pH 6.8) and shows a good permeability in the Caco-2 assay. MELK-8a inhibits the growth of MDA-MB-468 cells and MCF-7 cells with an IC50 of approximately 0.06 and 1.2 μM, respectively[1].

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

    體內(nèi)研究
    (In Vivo)

    Subcutaneous administration of MELK-8a at 30 mg/kg in C57BL/6 mice results in good plasma exposure. The compound adsorption into the systemic circulation is rapid (Tmax=0.4 h) and peak plasma concentration reaches 6.6 μM. An ascending dose PK study in female athymic nude mice shows that the rate of compound release is maximal at 120 mg/kg and all clearance mechanisms can be saturated at 240 mg/kg. However, when administered orally at 10 mg/kg in C57BL/6 male mice, it shows very poor PK (3.6% oral bioavailability) consistent with very high in vivo clearance[1].

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

    分子量

    469.02

    Formula

    C25H33ClN6O

    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

    4°C, sealed storage, away from moisture

    *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

    溶解性數(shù)據(jù)
    細胞實驗: 

    H2O 中的溶解度 : ≥ 100 mg/mL (213.21 mM)

    DMSO 中的溶解度 : 8.6 mg/mL (18.34 mM; 超聲加熱助溶; 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 2.1321 mL 10.6605 mL 21.3211 mL
    5 mM 0.4264 mL 2.1321 mL 4.2642 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,避免反復凍融造成的產(chǎn)品失效。
    儲備液的保存方式和期限:-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C儲存時,請在6個月內(nèi)使用,-20°C儲存時,請在1個月內(nèi)使用。

    * 備注:如您選擇水作為儲備液,請稀釋至工作液后,再用 0.22 μm 的濾膜過濾除菌后使用。

    • 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:

    以下溶解方案,請直接配制工作液。建議現(xiàn)用現(xiàn)配,在短期內(nèi)盡快用完。 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: PBS

      Solubility: 50 mg/mL (106.61 mM); 澄清溶液; 超聲助溶

    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

    由于實驗過程有損耗,建議您多配一只動物的量
    計算結果
    工作液所需濃度 : mg/mL
    該產(chǎn)品水溶性佳,請具體參考實測 水 / PBS / Saline 中的溶解度數(shù)據(jù)。
    您所需的儲備液濃度超過該產(chǎn)品的實測溶解度,如有需要,請與 MCE 中國技術支持聯(lián)系。
    純度 & 產(chǎn)品資料

    純度: 99.31%

    參考文獻
    Cell Assay
    [1]

    MDA-MB-468 and MCF7 cells are seeded in growth medium into 96-well plates at 1000 and 4000 cells/well, respectively. Sixteen hours after plating, MELK-8a are added and incubated for 7 days. For each well, ATPLite reagent is added and incubated. Luminescence is measured on an multilabel plate reader[1].

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

    Animal Administration
    [1]

    Mice: For pharmacokinetic studies, the intravenous and oral dose is prepared in a solution containing 5% ethanol, 100% PG, 5% CremophorEL, and 80% PBS. The subcutaneous dose is formulated in 10% PG and 25% (20%, v/v) Solutol. Plasma samples are collected at specified time points and stored frozen (?20 °C) until MELK-8a analysis. An LC?MS/MS method is used to quantitate MELK-8a drug levels in plasma[1].

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

    參考文獻

    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,避免反復凍融造成的產(chǎn)品失效。
    儲備液的保存方式和期限:-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C儲存時,請在6個月內(nèi)使用,-20°C儲存時,請在1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 / H2O 1 mM 2.1321 mL 10.6605 mL 21.3211 mL 53.3026 mL
    5 mM 0.4264 mL 2.1321 mL 4.2642 mL 10.6605 mL
    10 mM 0.2132 mL 1.0661 mL 2.1321 mL 5.3303 mL
    15 mM 0.1421 mL 0.7107 mL 1.4214 mL 3.5535 mL
    H2O 20 mM 0.1066 mL 0.5330 mL 1.0661 mL 2.6651 mL
    25 mM 0.0853 mL 0.4264 mL 0.8528 mL 2.1321 mL
    30 mM 0.0711 mL 0.3554 mL 0.7107 mL 1.7768 mL
    40 mM 0.0533 mL 0.2665 mL 0.5330 mL 1.3326 mL
    50 mM 0.0426 mL 0.2132 mL 0.4264 mL 1.0661 mL
    60 mM 0.0355 mL 0.1777 mL 0.3554 mL 0.8884 mL
    80 mM 0.0267 mL 0.1333 mL 0.2665 mL 0.6663 mL
    100 mM 0.0213 mL 0.1066 mL 0.2132 mL 0.5330 mL

    * 備注:如您選擇水作為儲備液,請稀釋至工作液后,再用 0.22 μm 的濾膜過濾除菌后使用。

    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:
    MELK-8a hydrochloride
    目錄號:
    HY-100368A
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