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

THZ1 Hydrochloride 

目录号: HY-80013A 纯度: 98.78%
COA 产品使用指南

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

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THZ1 Hydrochloride Chemical Structure

THZ1 Hydrochloride Chemical Structure

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3.  试用装只面向终端客户

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥994
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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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200 mg   询价  

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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 Hydrochloride 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 Hydrochloride 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 Hydrochloride 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 Hydrochloride 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 Hydrochloride 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 Hydrochloride 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 Hydrochloride 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 Hydrochloride 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 Hydrochloride 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 Hydrochloride 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 Hydrochloride 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 Hydrochloride 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 Hydrochloride is a selective and potent covalent CDK7 inhibitor with an IC50 of 3.2 nM. THZ1 Hydrochloride 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 Hydrochloride 抑制 Jurkat 细胞和 Loucy 细胞,IC50 分别为 50 nM 和 0.55 nM。THZ1 Hydrochloride 在体外表现出对 CDK7 的时间依赖性抑制和细胞内 CDK7 的共价结合。THZ1 Hydrochloride (9、27、83、250、750 和 2500 nM) 抑制 CDK12,但与 CDK7 相比浓度更高。THZ1 Hydrochloride (1 μM) 不可逆地抑制 RNAPII CTD 和 CAK 磷酸化。THZ1 Hydrochloride (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 Hydrochloride (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 Hydrochloride 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 Hydrochloride (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 Hydrochloride (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 Hydrochloride (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

    602.51

    Formula

    C31H29Cl2N7O2

    性状

    固体

    颜色

    White to yellow

    运输条件

    Room temperature in continental US; may vary elsewhere.

    储存方式

    4°C, sealed storage, away from moisture

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

    溶解性数据
    In Vitro: 

    DMSO 中的溶解度 : 22.5 mg/mL (37.34 mM; 超声加热助溶; 吸湿的 DMSO 对产品的溶解度有显著影响,请使用新开封的 DMSO)

    H2O 中的溶解度 : < 0.1 mg/mL (insoluble)

    配制储备液
    浓度 溶剂体积 质量 1 mg 5 mg 10 mg
    1 mM 1.6597 mL 8.2986 mL 16.5972 mL
    5 mM 0.3319 mL 1.6597 mL 3.3194 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 (sealed storage, away from moisture)。-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    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.17 mg/mL (3.60 mM); 澄清溶液

      此方案可获得 ≥ 2.17 mg/mL(饱和度未知)的澄清溶液。

      1 mL 工作液为例,取 100 μL 21.7 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。
    • 方案 二

      请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in Saline)

      Solubility: 2.17 mg/mL (3.60 mM); 悬浊液; 超声助溶

      此方案可获得 2.17 mg/mL的均匀悬浊液,悬浊液可用于口服和腹腔注射。

      1 mL 工作液为例,取 100 μL 21.7 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中,混合均匀。

      20% SBE-β-CD in Saline 的配制(4°C,储存一周):2 g SBE-β-CD(磺丁基醚 β-环糊精)粉末定容于 10 mL 的生理盐水中,完全溶解至澄清透明。
    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)。

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

    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: 98.78%

    参考文献
    Kinase Assay
    [1]

    For kinase assays following immunoprecipitation of FLAG-CDK7 protein from HCT116 or FLAG-CDK12 from 293A cellular lysates, cells are first treated with THZ1, THZ1-R, or DMSO for 4 hrs at 37°C. Cells are then harvested by lysis in 50 mM Tris HCl pH 8.0, 150 mM NaCl, 1% NP-40, 5 mM EDTA, and protease/phosphatase cocktails. Exogenous CDK7 or CDK12 proteins are immunoprecipitated from cellular lysates using FLAG antibody- conjugated agarose beads. Precipitated proteins are washed with lysis buffer 6 times, followed by 2 washes with kinase buffer (40 mM Hepes pH 7.5, 150 mM NaCl, 10 mM MgCl2, 5% glycerol) and subjected to in vitro kinase assays at 30°C for 45 minutes using 1 μg of the large subunit of RNAPII (RPB1) as substrate and 25 μM ATP and 10 μCi of 32P ATP. Note: no additional inhibitors are added to the kinase reaction mixture, therefore any inhibition results from the activity of the compounds that are added directly to cells (ie-intracellular inhibition). This suggests that the inhibitors are either covalently tethered to the kinase or have strong non-covalent character. Kinase assays using recombinant CDK7/TFIIH/MAT1 are conducted in the manner as described above using 25 ng of CAK complex per reaction. For kinase assays designed to test time-dependent inactivation of CDK7 kinase activity, CAK complex is pre-incubated with indicated concentrations of THZ1, THZ1-R, or DMSO in kinase buffer without ATP for 4 hrs at 30°C prior to being subjected to kinase assay conditions[1].

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

    Cell Assay
    [1]

    Jurkat, Loucy, KOPTK1, and DND-41 cell lines are seeded in 384-well microplates at 15% confluency in medium with 5% FBS and penicillin/streptavidin. 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 Hydrochloride 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 (sealed storage, away from moisture)。-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 1.6597 mL 8.2986 mL 16.5972 mL 41.4931 mL
    5 mM 0.3319 mL 1.6597 mL 3.3194 mL 8.2986 mL
    10 mM 0.1660 mL 0.8299 mL 1.6597 mL 4.1493 mL
    15 mM 0.1106 mL 0.5532 mL 1.1065 mL 2.7662 mL
    20 mM 0.0830 mL 0.4149 mL 0.8299 mL 2.0747 mL
    25 mM 0.0664 mL 0.3319 mL 0.6639 mL 1.6597 mL
    30 mM 0.0553 mL 0.2766 mL 0.5532 mL 1.3831 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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