1. Cell Cycle/DNA Damage
  2. CDK
  3. THZ1

THZ1 是有效,选择性的共价 CDK7 抑制剂,IC50 为 3.2 nM。THZ1 还抑制相关的激酶 CDK12CDK13,并下调 MYC 表达。

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THZ1 Chemical Structure

THZ1 Chemical Structure

CAS No. : 1604810-83-4

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规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥934
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1 mg ¥340
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5 mg ¥750
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10 mg ¥1400
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50 mg ¥6000
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Top Publications Citing Use of Products

MCE 顾客使用本产品发表的 72 篇科研文献

WB

    THZ1 purchased from MCE. Usage Cited in: Acta Pharmacol Sin. 2019 Jun;40(6):814-822.  [Abstract]

    The protein expression levels of the genes related to cell cycle and metabolism are detected by immunoblotting using the corresponding antibodies in H1299 cells treated with 20 nM THZ1 alone or in combination with 500 nM CB-839 for 48 h.

    THZ1 purchased from MCE. Usage Cited in: Oncogene. 2019 May;38(20):3932-3945.  [Abstract]

    Immunoblot analysis of the MYC and β-actin in cells (MiaPaCa2 and MiaPaCa2-R) treated with the indicated dose of THZ1 for 6 h.

    THZ1 purchased from MCE. Usage Cited in: Onco Targets Ther. 2019 Mar 22;12:2137-2147.   [Abstract]

    Western blot is used to assess the RNA Pol II protein and its phosphorylation at serine 2, serine 5, and serine 7 in cervical cancer cells after treatment with the indicated concentrations of THZ1.

    THZ1 purchased from MCE. Usage Cited in: Cell. 2018 Sep 20;175(1):171-185.e25.  [Abstract]

    WB analysis of MV4-11 cells treated with BTX161 (6 hr), iCDK9 (4 hr), or THZ1 (4 hr) at the indicated concentrations in different combinations as indicated. PP2Ac is a loading control.

    THZ1 purchased from MCE. Usage Cited in: Nat Commun. 2018 Aug 23;9(1):3392.  [Abstract]

    21mers are synthesized in parallel reactions with unlabeled (upper panel) or radiolabeled (lower panel) ribonucleoside triphosphates in the presence of DMSO (-) or increasing amounts of THZ1; reactions are stopped after 15 or 60 min.

    THZ1 purchased from MCE. Usage Cited in: Nat Commun. 2018 Nov 19;9(1):4866.  [Abstract]

    MYCN, PHOX2B, and TBX2 protein levels 10 h and 16 h upon treatment with 1 μM JQ1, 35 nM THZ1 and the combination of JQ1 and THZ1 in the IMR-5/75 cell line.

    THZ1 purchased from MCE. Usage Cited in: Oncogenesis. 2017 May 15;6(5):e336.  [Abstract]

    Lysates from cells treated with vehicle or 200 nM THZ1 for 48 h analyzed for the activation status of multiple CDKs as indicated to the right of panels by western blotting.

    THZ1 purchased from MCE. Usage Cited in: Mol Cancer Ther. 2017 Sep;16(9):1739-1750.  [Abstract]

    Western blot analysis of RNAPII CTD phosphorylation in ovarian cancer cells that are treated with THZ1.

    THZ1 purchased from MCE. Usage Cited in: Mol Cancer Ther. 2017 Sep;16(9):1739-1750.  [Abstract]

    Western blot analysis of RNAPII CTD phosphorylation in ovarian cancer cells that are treated with THZ1.

    THZ1 purchased from MCE. Usage Cited in: Mol Cancer Ther. 2017 Sep;16(9):1739-1750.  [Abstract]

    Western blot analysis of RNAPII CTD phosphorylation in ovarian cancer cells that are treated with THZ1.

    THZ1 purchased from MCE. Usage Cited in: TUMOR, 2017, 37(11): 1119-1127.

    The expression level of cyclin-dependent kinase 7 (CDK7) and the phosphorylation level of RNA polymeraseⅡ carboxyl-terminal domain Ser-5 (RNAPolⅡS5) in ovarian cancer cells treated with THZ1 are detected by Western blotting. After the ovarian cancer IGROV1, OVCA433, SKOV3 and COV413B cells are treated with 0.5 μM THZ1 for 0, 4, 8, 12 and 24 h, the CDK7 expression and RNAPolⅡS5 phosphorylation levels are significantly down-regulated.

    THZ1 purchased from MCE. Usage Cited in: Oncotarget. 2017 Apr 18;8(16):27353-27363.  [Abstract]

    Representative Western blot showing the phosphorylation status of ERα at serine 118 (S118) in MCF-7 cells in controls and after treatment with the CDK7 inhibitor, THZ1 (100 nM), or AG-490 (100 μM) for 3 h prior to E2 treatment for 30 min. Endogenous ERα and β-actin are used as loading controls.
    • 生物活性

    • 实验参考方法

    • 纯度 & 产品资料

    • 参考文献

    生物活性

    THZ1 is a selective and potent covalent CDK7 inhibitor with an IC50 of 3.2 nM. THZ1 also inhibits the closely related kinases CDK12 and CDK13 and downregulates MYC expression[1][2].

    IC50 & Target[1][2]

    CDK7

    3.2 nM (IC50)

    CDK12

     

    CDK13

     

    体外研究
    (In Vitro)

    THZ1 抑制 Jurkat 细胞和 Loucy 细胞,IC50 分别为 50 nM 和 0.55 nM。THZ1 (9、27、83、250、750 和 2500 nM) 抑制 CDK12,但与 CDK7 相比浓度更高。THZ1 (1 μM) 不可逆地抑制 RNAPII CTD 和 CAK 磷酸化。THZ1 (2.5 μM) 通过共价靶向位于 Hela S3 细胞 CDK7 激酶结构域外的独特半胱氨酸,不可逆地抑制 RNAPII CTD 磷酸化。THZ1 (250 nM) 导致细胞增殖减少和凋亡指数增加,同时抗凋亡蛋白减少,最显著的是 T-ALL 细胞系中的 MCL-1XIAP[1]
    所有基因型不同的人 (hSCLC) 细胞系都对 THZ1 表现出高度敏感性,IC50 范围为 5 -20 nM[3]

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

    体内研究
    (In Vivo)

    THZ1 (10 mg/kg) 表现出对原发性慢性淋巴细胞白血病 (CLL) 细胞的有效杀伤和对原发性 TALL 细胞以及体内对人 T-ALL 异种移植物的抗增殖活性[1]
    THZ1 (10 mg/kg,iv) 在人 MYCN 扩增的 NB 小鼠模型中抑制肿瘤生长并且没有显示出毒性[4]
    THZ1 (10 mg/kg,ip) 在体内完全抑制食管鳞状细胞癌肿瘤生长,而不会减轻体重或其他常见毒性作用[5]

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

    分子量

    566.05

    Formula

    C31H28ClN7O2

    CAS 号
    性状

    固体

    颜色

    Off-white to yellow

    运输条件

    Room temperature in continental US; may vary elsewhere.

    储存方式
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 6 months
    -20°C 1 month
    溶解性数据
    In Vitro: 

    DMSO 中的溶解度 : 100 mg/mL (176.66 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响,请使用新开封的 DMSO)

    Ethanol 中的溶解度 : < 1 mg/mL (insoluble)

    配制储备液
    浓度 溶剂体积 质量 1 mg 5 mg 10 mg
    1 mM 1.7666 mL 8.8331 mL 17.6663 mL
    5 mM 0.3533 mL 1.7666 mL 3.5333 mL
    查看完整储备液配制表

    * 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
    储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month。-80°C储存时,请在6个月内使用,-20°C储存时,请在1个月内使用。

    • 摩尔计算器

    • 稀释计算器

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

    质量
    =
    浓度
    ×
    体积
    ×
    分子量 *

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

    This equation is commonly abbreviated as: C1V1 = C2V2

    浓度 (start)

    C1

    ×
    体积 (start)

    V1

    =
    浓度 (final)

    C2

    ×
    体积 (final)

    V2

    In Vivo:

    请根据您的 实验动物和给药方式 选择适当的溶解方案。

    以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:
    ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用
    以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

    • 方案 一

      请依序添加每种溶剂: 10% DMSO    90% Saline

      Solubility: 5 mg/mL (8.83 mM); 悬浊液; 超声助溶

    • 方案 二

      请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (4.42 mM); 澄清溶液

      此方案可获得 ≥ 2.5 mg/mL(饱和度未知)的澄清溶液。

      1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;再向上述体系中加入 50 μL Tween-80,混合均匀;然后再继续加入 450 μL 生理盐水 定容至 1 mL

      生理盐水的配制:将 0.9 g 氯化钠,溶解于 ddH₂O 并定容至 100 mL,可以得到澄清透明的生理盐水溶液。
    动物溶解方案计算器
    请输入动物实验的基本信息:

    给药剂量

    mg/kg

    动物的平均体重

    g

    每只动物的给药体积

    μL

    动物数量

    由于实验过程有损耗,建议您多配一只动物的量
    请输入您的动物体内配方组成:
    %
    DMSO +
    +
    %
    Tween-80 +
    %
    Saline
    如果您的动物是免疫缺陷鼠或者体弱鼠,建议 DMSO 中的在最后工作液体系中的占比尽量不超过 2%。
    方案所需 助溶剂 包括:DMSO ,均可在 MCE 网站选购。 Tween 80,均可在 MCE 网站选购。
    计算结果
    工作液所需浓度 : mg/mL
    储备液配制方法 : mg 药物溶于 μL  DMSO(母液浓度为 mg/mL)。
    您所需的储备液浓度超过该产品的实测溶解度,以下方案仅供参考,如有需要,请与 MCE 中国技术支持联系。
    动物实验体内工作液的配制方法 : 取 μL DMSO 储备液,加入 μL  μL ,混合均匀至澄清,再加 μL Tween 80,混合均匀至澄清,再加 μL 生理盐水
    连续给药周期超过半月以上,请谨慎选择该方案。
    请确保第一步储备液溶解至澄清状态,从左到右依次添加助溶剂。您可采用超声加热 (超声清洗仪,建议频次 20-40 kHz),涡旋吹打等方式辅助溶解。
    纯度 & 产品资料

    纯度: 99.84%

    参考文献
    Cell Assay
    [1]

    Jurkat, Loucy, KOPTK1, and DND-41 cell lines are seeded in 384-well microplates at 15% confluency in medium. Cells are treated with THZ1 (2, 10, 50, 250, 1250, and 6250 nM) or DMSO for 72 hrs and cell viability is determined using resazurin[1].

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

    Animal Administration
    [1]

    Mice[1]
    Thirty-two NOD-SCIDIL2Rcγnull (NSG) 9-week old female mice are divided into treatment groups based on mean BLI as follows: THZ1 10 mg/kg qD, THZ1 10 mg/kg BID, and vehicle (10% DMSO in D5W) BID (n=10 for all groups). Two mice are excluded, one with the highest and one with the lowest BLI. All treatments are administered via IV injection in the lateral tail vein in a volume of 3.3 μL/g (non-blinded). Mice are imaged and weighed every 3-5 days. Mice are treated for four weeks and on the final day mice are imaged, dosed and sacrificed approximately 5-6 hrs post dose. Upon sacrifice, blood is collected via cardiac puncture in EDTA tubes; a portion (300 uL) is processed for plasma. Liver and spleen tissues are collected from each mouse with half of each sample flash frozen and half of each sample fixed. Blood plasma and liver samples are processed for pharmacokinetics analysis of THZ1. Spleen tissues are homogenized and lysed and processed for pharmacodynamics analysis of THZ1 target engagement.

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

    参考文献

    THZ1 相关分类

    完整储备液配制表

    * 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
    储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month。-80°C储存时,请在6个月内使用,-20°C储存时,请在1个月内使用。

    可选溶剂 浓度 溶剂体积 质量 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 1.7666 mL 8.8331 mL 17.6663 mL 44.1657 mL
    5 mM 0.3533 mL 1.7666 mL 3.5333 mL 8.8331 mL
    10 mM 0.1767 mL 0.8833 mL 1.7666 mL 4.4166 mL
    15 mM 0.1178 mL 0.5889 mL 1.1778 mL 2.9444 mL
    20 mM 0.0883 mL 0.4417 mL 0.8833 mL 2.2083 mL
    25 mM 0.0707 mL 0.3533 mL 0.7067 mL 1.7666 mL
    30 mM 0.0589 mL 0.2944 mL 0.5889 mL 1.4722 mL
    40 mM 0.0442 mL 0.2208 mL 0.4417 mL 1.1041 mL
    50 mM 0.0353 mL 0.1767 mL 0.3533 mL 0.8833 mL
    60 mM 0.0294 mL 0.1472 mL 0.2944 mL 0.7361 mL
    80 mM 0.0221 mL 0.1104 mL 0.2208 mL 0.5521 mL
    100 mM 0.0177 mL 0.0883 mL 0.1767 mL 0.4417 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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    产品名称:
    THZ1
    目录号:
    HY-80013
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