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  2. Apoptosis
  3. Bcl-2 Family Apoptosis
  4. A-1210477

A-1210477 是一種有效，選擇性的 MCL-1 抑制劑，Ki 值為 0.45 nM。A-1210477 特異性結(jié)合 MCL-1，并以 MCL-1 依賴性方式促進(jìn)癌細(xì)胞凋亡 (apoptosis)。

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A-1210477 Chemical Structure

A-1210477 Chemical Structure

CAS No. : 1668553-26-1

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25 mg ￥2000
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100 mg ￥5500
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    A-1210477 purchased from MCE. Usage Cited in: Clin Res Hepatol Gas. 2019 Jun;43(3):292-300.  [Abstract]

    S63845 and A-1210477 trigger apoptosis signaling and reduce the levels of putative stem biomarkers in HCC cell lines.

    A-1210477 purchased from MCE. Usage Cited in: Open Biol. 2016 Aug;6(8). pii: 160134.  [Abstract]

    Immunoblots showing affinity purification of GFP-tagged Mcl-1 in the presence of 2 μM A-1210477, and detection of co-purifying Bak.

    查看 Bcl-2 Family 亞型特異性產(chǎn)品:

    • 生物活性

    • 實(shí)驗(yàn)參考方法

    • 純度 & 產(chǎn)品資料

    • 參考文獻(xiàn)

    生物活性

    A-1210477 is a potent and selective inhibitor of MCL-1 with a Ki of 0.45 nM[1]. A-1210477 specifically binds MCL-1 and promotes apoptosis of cancer cells in an MCL-1-dependent manner[2].

    IC50 & Target[1]

    Mcl-1

    0.45 nM (Ki)

    Bcl-2

    132 nM (Ki)

    Bfl-1

    660 nM (Ki)

    Bcl-W

    2280 nM (Ki)

    Apoptosis

     

    細(xì)胞效力
    (Cellular Effect)
    Cell Line Type Value Description References
    HEK-293T IC50
    > 20 μM
    Compound: A1210477
    Cytotoxicity against HEK293T cells assessed as reduction in cell viability incubated for 48 hrs by CCK8 assay
    Cytotoxicity against HEK293T cells assessed as reduction in cell viability incubated for 48 hrs by CCK8 assay
    		[PMID: 34228434]
    HeLa IC50
    > 20 μM
    Compound: A1210477
    Cytotoxicity against human HeLa cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
    Cytotoxicity against human HeLa cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
    		[PMID: 34228434]
    HL-60 IC50
    2.46 μM
    Compound: A1210477
    Cytotoxicity against human HL-60 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
    Cytotoxicity against human HL-60 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
    		[PMID: 34228434]
    K562 IC50
    > 30 μM
    Compound: 4; A1210477
    Antiproliferative activity against human K562 cells assessed as decrease in cell viability measured after 72 hrs by MTT assay
    Antiproliferative activity against human K562 cells assessed as decrease in cell viability measured after 72 hrs by MTT assay
    		[PMID: 34342996]
    K562 IC50
    13.9 μM
    Compound: A-1210477
    Cytotoxicity against human K562 cells after 24 hrs by MTT assay
    Cytotoxicity against human K562 cells after 24 hrs by MTT assay
    		[PMID: 32794745]
    KMS-12-PE IC50
    > 40 μM
    Compound: A-1210477
    Cytotoxicity against human KMS-12-PE cells after 24 hrs by MTT assay
    Cytotoxicity against human KMS-12-PE cells after 24 hrs by MTT assay
    		[PMID: 32794745]
    L-363 IC50
    11.8 μM
    Compound: A-1210477
    Cytotoxicity against human L-363 cells after 24 hrs by MTT assay
    Cytotoxicity against human L-363 cells after 24 hrs by MTT assay
    		[PMID: 32794745]
    LP-1 IC50
    10.6 μM
    Compound: A-1210477
    Cytotoxicity against human LP-1 cells after 24 hrs by MTT assay
    Cytotoxicity against human LP-1 cells after 24 hrs by MTT assay
    		[PMID: 32794745]
    MM1.S IC50
    > 40 μM
    Compound: A-1210477
    Cytotoxicity against human MM1.S cells after 24 hrs by MTT assay
    Cytotoxicity against human MM1.S cells after 24 hrs by MTT assay
    		[PMID: 32794745]
    MV4-11 IC50
    1.55 μM
    Compound: 4; A1210477
    Antiproliferative activity against human MV4-11 cells assessed as decrease in cell viability measured after 72 hrs by MTT assay
    Antiproliferative activity against human MV4-11 cells assessed as decrease in cell viability measured after 72 hrs by MTT assay
    		[PMID: 34342996]
    NCI-H23 IC50
    13.5 μM
    Compound: 4; A1210477
    Antiproliferative activity against human NCI-H23 cells assessed as decrease in cell viability measured after 72 hrs by MTT assay
    Antiproliferative activity against human NCI-H23 cells assessed as decrease in cell viability measured after 72 hrs by MTT assay
    		[PMID: 34342996]
    NCI-H929 IC50
    0.9 μM
    Compound: 4; A1210477
    Antiproliferative activity against human NCI-H929 cells assessed as decrease in cell viability measured after 72 hrs by MTT assay
    Antiproliferative activity against human NCI-H929 cells assessed as decrease in cell viability measured after 72 hrs by MTT assay
    		[PMID: 34342996]
    NCI-H929 IC50
    8.6 μM
    Compound: A-1210477
    Cytotoxicity against human NCI-H929 cells after 24 hrs by MTT assay
    Cytotoxicity against human NCI-H929 cells after 24 hrs by MTT assay
    		[PMID: 32794745]
    RS4-11 IC50
    7.31 μM
    Compound: A1210477
    Cytotoxicity against human RS4-11 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
    Cytotoxicity against human RS4-11 cells assessed as inhibition of cell growth incubated for 48 hrs by CCK8 assay
    		[PMID: 34228434]
    SK-BR-3 IC50
    4.31 μM
    Compound: 4; A1210477
    Antiproliferative activity against human SK-BR-3 cells assessed as decrease in cell viability measured after 72 hrs by MTT assay
    Antiproliferative activity against human SK-BR-3 cells assessed as decrease in cell viability measured after 72 hrs by MTT assay
    		[PMID: 34342996]
    體外研究
    (In Vitro)

    A-1210477 (10?μM) reduces the amount of BIM co-immunoprecipitated with MCL-1 antibody, and triggers MCL-1 elevation in a variety of cancer cell lines, including the breast cancer cell line HCC-1806. A-1210477 inhibits MCL-1-NOXA interactions with an IC50 of approximately 1?μM, while having no effect on BCL-2-BIM or BCL-XL-BCL-XS interactions. The NSCLC cell lines H2110 and H23 are sensitive to A-1210477 with cell viability IC50<10?μM, confirming that A-1210477 can kill MCL-1-dependent cell lines[1].

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

    850.04

    Formula

    C46H55N7O7S
    CAS 號(hào)
    性狀

    固體

    顏色

    White to off-white

    運(yùn)輸條件

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

    DMSO 中的溶解度 : 10 mg/mL (11.76 mM; 超聲助溶; 吸濕的 DMSO 對(duì)產(chǎn)品的溶解度有顯著影響，請(qǐng)使用新開封的 DMSO)

    配制儲(chǔ)備液
    濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg
    1 mM 1.1764 mL 5.8821 mL 11.7642 mL
    5 mM 0.2353 mL 1.1764 mL 2.3528 mL
    查看完整儲(chǔ)備液配制表

    * 請(qǐng)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(chǔ)備液；一旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
    儲(chǔ)備液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?年內(nèi)使用， -20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?年內(nèi)使用。

    • 摩爾計(jì)算器

    • 稀釋計(jì)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(dòng)物實(shí)驗(yàn)：

    請(qǐng)根據(jù)您的 實(shí)驗(yàn)動(dòng)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(qǐng)先按照 In Vitro 方式配制澄清的儲(chǔ)備液，再依次添加助溶劑：
    ——為保證實(shí)驗(yàn)結(jié)果的可靠性，澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)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(qǐng)依序添加每種溶劑： 10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 1 mg/mL (1.18 mM); 澄清溶液

      此方案可獲得 ≥ 1 mg/mL（飽和度未知）的澄清溶液。

      以 1 mL 工作液為例，取 100 μL 10.0 mg/mL 的澄清 DMSO 儲(chǔ)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(qǐng)依序添加每種溶劑： 10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: 1 mg/mL (1.18 mM); 懸濁液; 超聲助溶

      此方案可獲得 1 mg/mL的均勻懸濁液，懸濁液可用于口服和腹腔注射。

      以 1 mL 工作液為例，取 100 μL 10.0 mg/mL 的澄清 DMSO 儲(chǔ)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(dòng)物溶解方案計(jì)算器
    請(qǐng)輸入動(dòng)物實(shí)驗(yàn)的基本信息：

    給藥劑量

    mg/kg

    動(dòng)物的平均體重

    g

    每只動(dòng)物的給藥體積

    μL

    動(dòng)物數(shù)量

    只
    由于實(shí)驗(yàn)過程有損耗，建議您多配一只動(dòng)物的量
    請(qǐng)輸入您的動(dòng)物體內(nèi)配方組成：
    %
    DMSO +
    % 
    +
    %
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    %
    Saline
    如果您的動(dòng)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(gòu)。 ，Tween 80，均可在 MCE 網(wǎng)站選購(gòu)。
    計(jì)算結(jié)果
    工作液所需濃度 : mg/mL
    儲(chǔ)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(chǔ)備液濃度超過該產(chǎn)品的實(shí)測(cè)溶解度，以下方案僅供參考，如有需要，請(qǐng)與 MCE 中國(guó)技術(shù)支持聯(lián)系。
    動(dòng)物實(shí)驗(yàn)體內(nèi)工作液的配制方法 : 取 μL DMSO 儲(chǔ)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(qǐng)謹(jǐn)慎選擇該方案。
    請(qǐng)確保第一步儲(chǔ)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: 99.40%

    參考文獻(xiàn)
    Kinase Assay
    [1]

    TR-FRET-binding affinity assays are performed for BCL-2, BCL-XL, and MCL-1 in 4.52?mM monobasic potassium phosphate, 15.48?mM dibasic potassium phosphate, 1?mM sodium EDTA, 0.05% Pluronic F-68 detergent, 50?mM sodium chloride, and 1?mM DTT (pH 7.5) for BCL-XL.6 For MCL-1 assays, GST-tagged MCL-1 (1?nM) is mixed with 100?nM f-Bak, 1?nM Tb-labeled anti-GST antibody, and compound at room temperature (RT) for 60?min. Fluorescence is measured on an Envision plate reader using a 340/35?nm excitation filter and 520/525 (f-Bak) and 495/510?nm (Tb-labeled anti-GST antibody) emission filters.

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

    Adherent cell lines are seeded at 50?000 cells per well in 96-well plates and treated for 48?h with compounds diluted in half-log steps starting at 30?μM and ending at 0.001?μM. Multiple myeloma cell lines are seeded at 15?000-20?000 cells per well and treated similarly. Effects on proliferation and viability are determined using CellTiter-Glo reagent from Promega according to the manufacturer's instructions. IC50 values are determined by non-linear regression analysis of the concentration response data.

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

    完整儲(chǔ)備液配制表

    * 請(qǐng)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(chǔ)備液；一旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
    儲(chǔ)備液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?年內(nèi)使用， -20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?年內(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 1.1764 mL 5.8821 mL 11.7642 mL 29.4104 mL
    5 mM 0.2353 mL 1.1764 mL 2.3528 mL 5.8821 mL
    10 mM 0.1176 mL 0.5882 mL 1.1764 mL 2.9410 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：
    A-1210477
    目錄號(hào)：
    HY-12468
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