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  2. Apoptosis Metabolic Enzyme/Protease
  3. MDM-2/p53 E1/E2/E3 Enzyme
  4. Navtemadlin

Navtemadlin  (Synonyms: AMG 232; KRT-232)

目錄號(hào): HY-12296 純度: 99.61%
COA 產(chǎn)品使用指南

Navtemadlin (AMG 232) 是一種有效，選擇性，可口服的 p53-MDM2 相互作用抑制劑，IC50 值為 0.6 nM，與 MDM2 結(jié)合的 Kd 為 0.045 nM。

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Navtemadlin Chemical Structure

Navtemadlin Chemical Structure

CAS No. : 1352066-68-2

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規(guī)格 價(jià)格 是否有貨 數(shù)量
1 mg ￥685
In-stock
5 mg ￥1700
In-stock
10 mg ￥2300
In-stock
25 mg ￥3800
In-stock
50 mg ￥5300
In-stock
100 mg   詢(xún)價(jià)  
200 mg   詢(xún)價(jià)  

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Customer Review

Other Forms of Navtemadlin:

    Navtemadlin purchased from MCE. Usage Cited in: Cell Death Discov. 2020 Jul 6;6:57.  [Abstract]

    The effect of AMG-232 on the p53 signaling pathway, and the expression of IL-6 and PD-L1 at different drug doses is assessed by immunoblotting. AMG-232 treatment leads to activation of the p53 signaling pathway in the cancer cells in a dose-dependent manner. The effect of significant reduction in IL-6 expression is observed with AMG-232 in a dose-dependent manner.

    • 生物活性

    • 純度 & 產(chǎn)品資料

    • 參考文獻(xiàn)

    生物活性

    Navtemadlin (AMG 232) is a potent, selective and orally available inhibitor of p53-MDM2 interaction, with an IC50 of 0.6 nM. Navtemadlin binds to MDM2 with a Kd of 0.045 nM[1][2].

    IC50 & Target

    IC50: 0.6 nM (p53-MDM2 interaction)[1]
    Kd: 0.045 nM (MDM2)[1]
    細(xì)胞效力
    (Cellular Effect)
    Cell Line Type Value Description References
    HCT-116 IC50
    > 25 μM
    Compound: 2, AMG 232
    Antiproliferative activity against p53 -deficient human HCT116 cells after 16 hrs by BrdU proliferation assay
    Antiproliferative activity against p53 -deficient human HCT116 cells after 16 hrs by BrdU proliferation assay
    		[PMID: 24456472]
    HCT-116 IC50
    10 nM
    Compound: 2, AMG 232
    Antiproliferative activity against human HCT116 cells expressing p53 wild type after 16 hrs by BrdU proliferation assay
    Antiproliferative activity against human HCT116 cells expressing p53 wild type after 16 hrs by BrdU proliferation assay
    		[PMID: 24456472]
    HCT-116 GI50
    33 μM
    Compound: AMG 232
    Antiproliferative activity against human HCT116 p53-/- cells assessed as growth inhibition after 24 hrs by EdU/Hoechst 33342 staining-based fluorescence analysis
    Antiproliferative activity against human HCT116 p53-/- cells assessed as growth inhibition after 24 hrs by EdU/Hoechst 33342 staining-based fluorescence analysis
    		[PMID: 29691156]
    HCT-116 GI50
    7 μM
    Compound: AMG 232
    Antiproliferative activity against human HCT116 p53+/+ cells assessed as growth inhibition after 24 hrs by EdU/Hoechst 33342 staining-based fluorescence analysis
    Antiproliferative activity against human HCT116 p53+/+ cells assessed as growth inhibition after 24 hrs by EdU/Hoechst 33342 staining-based fluorescence analysis
    		[PMID: 29691156]
    SJSA-1 ED50
    2.8 nM
    Compound: 2, AMG 232
    Antiproliferative activity against human SJSA1 cells xenografted in athymic nude mouse assessed as unbound concentration causing inhibition of tumor growth treated after 11 days of tumor xenograft upto 25 days through oral gavage relative to vehicle treat
    Antiproliferative activity against human SJSA1 cells xenografted in athymic nude mouse assessed as unbound concentration causing inhibition of tumor growth treated after 11 days of tumor xenograft upto 25 days through oral gavage relative to vehicle treat
    		[PMID: 24456472]
    SJSA-1 IC50
    47 nM
    Compound: 1, AMG 232
    Binding affinity to MDM2 in human SJSA1 cells assessed as induction of p21 gene level after 7 hrs by qRT-PCR assay in presence of 10% human serum
    Binding affinity to MDM2 in human SJSA1 cells assessed as induction of p21 gene level after 7 hrs by qRT-PCR assay in presence of 10% human serum
    		[PMID: 25384157]
    SJSA-1 ED50
    9.1 mg/kg
    Compound: 2, AMG 232
    Antiproliferative activity against human SJSA1 cells xenografted in athymic nude mouse assessed as inhibition of tumor growth treated after 11 days of tumor xenograft upto 25 days through oral gavage relative to vehicle treated control
    Antiproliferative activity against human SJSA1 cells xenografted in athymic nude mouse assessed as inhibition of tumor growth treated after 11 days of tumor xenograft upto 25 days through oral gavage relative to vehicle treated control
    		[PMID: 24456472]
    SJSA-1 IC50
    9.1 nM
    Compound: 2, AMG 232
    Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 1 hr by Click-iT EdU HCS assay in presence of 10% human serum
    Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 1 hr by Click-iT EdU HCS assay in presence of 10% human serum
    		[PMID: 24456472]
    SJSA-1 IC50
    9.2 nM
    Compound: 1, AMG 232
    Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 16 hrs by Click-iT EdU HCS assay in presence of 10% human serum
    Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 16 hrs by Click-iT EdU HCS assay in presence of 10% human serum
    		[PMID: 25384157]
    體外研究
    (In Vitro)

    Navtemadlin (AMG 232) (10 μM) 誘導(dǎo) p53 信號(hào)傳導(dǎo)并抑制三種 p53 野生型腫瘤細(xì)胞系中的腫瘤細(xì)胞增殖[1]。
    Navtemadlin 能有效抑制非 MDM2 擴(kuò)增的 HCT116 結(jié)直腸細(xì)胞的增殖 (IC50=10 nM)[3]。

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

    Cell Viability Assay[1]

    Cell Line: SJSA-1, HCT116, ACHN, NCI-H460, MOLM-13, RKO, MCF7, 22RV1, HT-29, PC-3, NCI-H82, NCI-SNU1, MG-63, NCI-H2452, SW982, C32, SK-HEP-1, A375, RT4, RPMI2650, MDA-MB-134-VI, NCI-H2347 and A427 cells.
    Concentration: 0-10 μM.
    Incubation Time: 72 hours.
    Result: Induced p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines (SJSA-1, HCT116, and ACHN).
    Caused robust p21 mRNA induction between 9.76 and 34.9 fold with IC50 values ranging from 12.8 to 46.8 nM.
    體內(nèi)研究
    (In Vivo)

    Navtemadlin (AMG 232)（10、25、75 mg/kg，每日一次，口服）可在體內(nèi)激活 p53 通路活性[1]。
    Navtemadlin（10、25、75 mg/kg，每日一次，口服）能有效抑制小鼠腫瘤異種移植瘤的生長(zhǎng)[1]。
    Navtemadlin（10、25、75 mg/kg，每日一次，口服）可阻斷 DNA 合成并誘導(dǎo)體內(nèi)細(xì)胞凋亡[1]。
    Navtemadlin 會(huì)導(dǎo)致劑量依賴(lài)性腫瘤生長(zhǎng)抑制，ED50 為 16 mg/kg[2]。

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

    Animal Model: Female athymic nude mice (n=10/group) based cancer models[1].
    Dosage: 10, 25, 75 mg/kg.
    Administration: Once daily by oral gavage.
    Result: Resulted in significant tumor growth inhibition across all models. SJSA-1, an MDM2 amplified osteosarcoma model, was the most sensitive to AMG 232 treatment with an ED50 of 9.1 mg/kg. In the highest dose group of 75 mg/kg, 10/10 tumors completely regressed and were undetectable after 10 days of treatment.
    Clinical Trial
    分子量

    568.55

    Formula

    C28H35Cl2NO5S
    CAS 號(hào)
    性狀

    固體

    顏色

    White to light yellow

    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

    *該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)用現(xiàn)配，即刻使用。

    溶解性數(shù)據(jù)
    細(xì)胞實(shí)驗(yàn)： 

    DMSO 中的溶解度 : ≥ 50 mg/mL (87.94 mM; 吸濕的 DMSO 對(duì)產(chǎn)品的溶解度有顯著影響，請(qǐng)使用新開(kāi)封的 DMSO)

    * "≥" means soluble, but saturation unknown.

    配制儲(chǔ)備液
    濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg
    1 mM 1.7589 mL 8.7943 mL 17.5886 mL
    5 mM 0.3518 mL 1.7589 mL 3.5177 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；該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)用現(xiàn)配，即刻使用。

    • 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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)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: ≥ 2.5 mg/mL (4.40 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(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% Corn Oil

      Solubility: ≥ 2.5 mg/mL (4.40 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，此方案實(shí)驗(yàn)周期在半個(gè)月以上的動(dòng)物實(shí)驗(yàn)酌情使用。

      以 1 mL 工作液為例，取 100 μL 25.0 mg/mL 的澄清 DMSO 儲(chǔ)備液加到 900 μL玉米油中，混合均勻。

    以下溶解方案，請(qǐng)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的方式助溶。

    • 方案 一

      請(qǐng)依序添加每種溶劑： PBS

      Solubility: 1.5 mg/mL (2.64 mM); 澄清溶液; 超聲助溶

    • 方案 二

      請(qǐng)依序添加每種溶劑： 50% PEG300    50% Saline

      Solubility: 10 mg/mL (17.59 mM); 懸濁液; 超聲助溶

    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(guò)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 +
    % 
    +
    %
    Tween-80 +
    %
    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(guò) 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）。

    *該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)用現(xiàn)配，即刻使用。

    您所需的儲(chǔ)備液濃度超過(guò)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(guò)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: 99.61%

    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；該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)用現(xiàn)配，即刻使用。

    可選溶劑 濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.7589 mL 8.7943 mL 17.5886 mL 43.9715 mL
    5 mM 0.3518 mL 1.7589 mL 3.5177 mL 8.7943 mL
    10 mM 0.1759 mL 0.8794 mL 1.7589 mL 4.3972 mL
    15 mM 0.1173 mL 0.5863 mL 1.1726 mL 2.9314 mL
    20 mM 0.0879 mL 0.4397 mL 0.8794 mL 2.1986 mL
    25 mM 0.0704 mL 0.3518 mL 0.7035 mL 1.7589 mL
    30 mM 0.0586 mL 0.2931 mL 0.5863 mL 1.4657 mL
    40 mM 0.0440 mL 0.2199 mL 0.4397 mL 1.0993 mL
    50 mM 0.0352 mL 0.1759 mL 0.3518 mL 0.8794 mL
    60 mM 0.0293 mL 0.1466 mL 0.2931 mL 0.7329 mL
    80 mM 0.0220 mL 0.1099 mL 0.2199 mL 0.5496 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.

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    產(chǎn)品名稱(chēng)：
    Navtemadlin
    目錄號(hào)：
    HY-12296
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