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  1. Cell Cycle/DNA Damage PI3K/Akt/mTOR
  2. ATM/ATR
  3. AZ20

AZ20 是一種有效的,選擇性的 ATR 抑制劑,IC50 值為 5 nM;同時(shí)可抑制 mTOR 活性,IC50 值為 38 nM。

MCE 的所有產(chǎn)品僅用作科學(xué)研究或藥證申報(bào),我們不為任何個(gè)人用途提供產(chǎn)品和服務(wù)

AZ20 Chemical Structure

AZ20 Chemical Structure

CAS No. : 1233339-22-4

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規(guī)格 價(jià)格 是否有貨 數(shù)量
10 mM * 1 mL in DMSO ¥660
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1 mg ¥272
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5 mg ¥600
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10 mg ¥900
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50 mg ¥2900
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100 mg ¥4500
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Customer Review

    AZ20 purchased from MCE. Usage Cited in: Cell Death Dis. 2017 Aug 10;8(8):e2982.  [Abstract]

    Tumor pieces from M130116 PDXs treated with the vehicle or the RVX2135/AZ20 combination treatment are subjected to western blot analysis.

    查看 ATM/ATR 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

    AZ20 is a potent and selective inhibitor of ATR with an IC50 of 5 nM, and has 8-fold selectivity against mTOR (IC50=38 nM).

    IC50 & Target[1]

    ATR

    5 nM (IC50)

    mTOR

    38 nM (IC50)

    PI3Kα

    13000 nM (IC50)

    細(xì)胞效力
    (Cellular Effect)
    Cell Line Type Value Description References
    A549 IC50
    0.7 μM
    Compound: AZ20
    Cytotoxicity against human A549 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay
    Cytotoxicity against human A549 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay
    [PMID: 35191694]
    HeLa IC50
    0.005 μM
    Compound: 6, AZ20
    Inhibition of ATR in human HeLa cell nuclear extracts using glutathione S-transferase-p53N66 and ATP as substrate incubated for 10 mins prior to ATP addition measured after 1 hr by ELISA
    Inhibition of ATR in human HeLa cell nuclear extracts using glutathione S-transferase-p53N66 and ATP as substrate incubated for 10 mins prior to ATP addition measured after 1 hr by ELISA
    [PMID: 23394205]
    HT-29 IC50
    0.05 μM
    Compound: 6, AZ20
    Inhibition of ATR-mediated CHK1 phosphorylation at serine 345 in human HT29 cells after 1 hr in presence of 4-nitroquinoline 1-oxide
    Inhibition of ATR-mediated CHK1 phosphorylation at serine 345 in human HT29 cells after 1 hr in presence of 4-nitroquinoline 1-oxide
    [PMID: 23394205]
    HT-29 GI50
    0.97 μM
    Compound: 1; AZ20
    Cytotoxicity against human HT-29 cells after 72 hrs by MTS assay
    Cytotoxicity against human HT-29 cells after 72 hrs by MTS assay
    [PMID: 30346772]
    LoVo GI50
    0.2 μM
    Compound: 1; AZ20
    Cytotoxicity against human LoVo cells after 72 hrs by MTS assay
    Cytotoxicity against human LoVo cells after 72 hrs by MTS assay
    [PMID: 30346772]
    LoVo GI50
    0.2 μM
    Compound: 6, AZ20
    Growth inhibition of human LoVo cells after 72 hrs by MTS assay
    Growth inhibition of human LoVo cells after 72 hrs by MTS assay
    [PMID: 23394205]
    體外研究
    (In Vitro)

    AZ20 抑制 HeLa 核提取物中免疫沉淀的 ATR,IC50 為 5 nM,ATR 介導(dǎo)的 Chk1 磷酸化在 HT29 結(jié)直腸腺癌腫瘤細(xì)胞中的 IC50 為 50 nM[1]

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

    體內(nèi)研究
    (In Vivo)

    AZ20 (25、50 mg/kg,口服) 具有高滲透性和對(duì)大鼠肝細(xì)胞的良好穩(wěn)定性,盡管在實(shí)現(xiàn)顯著更高的溶解度方面缺乏進(jìn)展,但在低劑量大鼠 PK 研究中具有可觀(guān)的生物利用度。AZ20 (25,50 mg/kg,po) 對(duì)攜帶 LoVo 腫瘤的雌性裸鼠顯著抑制腫瘤生長(zhǎng)[1]。

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

    分子量

    412.51

    Formula

    C21H24N4O3S

    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 : ≥ 100 mg/mL (242.42 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 2.4242 mL 12.1209 mL 24.2418 mL
    5 mM 0.4848 mL 2.4242 mL 4.8484 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(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 (6.06 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。

      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% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.5 mg/mL (6.06 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。

      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 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

    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)。
    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: 99.40%

    參考文獻(xiàn)
    Cell Assay
    [1]

    Compound dose ranges are created by diluting in 100% DMSO and then further into assay medium (EMEM, 10% FCS, 1% glutamine) using a Labcyte Echo acoustic dispensing instrument. Cells are plated in 384-well Costar plates at 9×104?cells per mL in 40 μL of EMEM, 10% FCS, 1% glutamine and grown for 24 h. Following addition of compound the cells are incubated for 60 min. A final concentration of 3 μM?4NQO?(prepared in 100% DMSO) is then added using the Labcyte Echo, and the cells are incubated for a further 60 min. The cells are fixed by adding 40 μL of 3.7% v/v formaldehyde solution for 20 min. After removal of fix, cells are washed with PBS and permeabilized in 40 μL of PBS containing 0.1% Triton X-100. The cells are then washed, and 15 μL primary antibody solution (pChk1 Ser345) is added. The plates are incubated at 4°C overnight. The primary antibody is then washed off, and 20 μL of secondary antibody solution and 1 μM Hoechst 33258 added for 90 min at room temperature. The plates are washed and left in 40 μL of PBS. Plates are then read on an ArrayScan VTI instrument to determine staining intensities, and dose responses are obtained and used to determine the IC50?values for the compounds.

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

    Animal Administration
    [1]

    Female Swiss nu/nu mice are housed in negative pressure isolators. LoVo tumor xenografts are established in 8- to 12-week-old mice by injecting 1×107?tumor cells subcutaneously (100 μL in serum free medium) on the left dorsal flank. Animals are randomized into treatment groups when tumors become palpable. AZ20?is prepared in 10% DMSO/40% propylene glycol/50% water and administered orally. Tumors are measured up to three times per week with calipers. Tumor volumes are calculated and the data plotted using the geometric mean for each group versus time.

    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 2.4242 mL 12.1209 mL 24.2418 mL 60.6046 mL
    5 mM 0.4848 mL 2.4242 mL 4.8484 mL 12.1209 mL
    10 mM 0.2424 mL 1.2121 mL 2.4242 mL 6.0605 mL
    15 mM 0.1616 mL 0.8081 mL 1.6161 mL 4.0403 mL
    20 mM 0.1212 mL 0.6060 mL 1.2121 mL 3.0302 mL
    25 mM 0.0970 mL 0.4848 mL 0.9697 mL 2.4242 mL
    30 mM 0.0808 mL 0.4040 mL 0.8081 mL 2.0202 mL
    40 mM 0.0606 mL 0.3030 mL 0.6060 mL 1.5151 mL
    50 mM 0.0485 mL 0.2424 mL 0.4848 mL 1.2121 mL
    60 mM 0.0404 mL 0.2020 mL 0.4040 mL 1.0101 mL
    80 mM 0.0303 mL 0.1515 mL 0.3030 mL 0.7576 mL
    100 mM 0.0242 mL 0.1212 mL 0.2424 mL 0.6060 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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    Inquiry Information

    產(chǎn)品名稱(chēng):
    AZ20
    目錄號(hào):
    HY-15557
    需求量: