THZ2
目录号 : GC13511
A Cdk7 inhibitor
Cas No.:1604810-84-5
Sample solution is provided at 25 µL, 10mM.
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THZ2 is a potent and selective CDK7 inhibitor (IC50=13.9 nM).
Cyclin-dependent kinase (CDK) is a group of serine/threonine kinases. It is activated by binding to cyclin and participates in the regulation of cell cycle.
THZ2 selectively targets CDK7 and potently blocks the proliferation of triple-negative breast cancer (TNBC) cells and induces apoptotic cell death without causing alteration in cell cycle. The low nanomolar dose of THZ2 also inhibits the clonogenic growth of TNBC cells with IC50 of 10 nM.
THZ2 is well tolerant in mice as 10 mg/kg intraperitoneal treatment of THZ2 twice daily does not cause weight loss or behavioral changes. THZ2 treatment also significantly reduces the tumor growth rate mice. In addition, both acute (50 hr) or chronic (25 days) exposure to THZ markedly decreases CTD phosphorylation of RNAPII at all three phosphorylation sites as indication of CDk7 being efficiently targeted.
Reference:
1. Wang Y, Zhang T, Kwiatkowski N et al. CDK7-dependent transcriptional addiction in triple-negative breast cancer. Cell. 2015 Sep 24;163(1):174-86.
| Cell experiment [1]: | |
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Cell lines |
TNBC cells |
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Preparation method |
The solubility of this compound in DMSO is > 28.3 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
0.1 ~ 10000 nM; 7 days |
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Applications |
At low nanomolar doses, THZ2 efficiently suppressed the cell growth of TNBC cells (IC50 = ~ 10 nM). Besides, THZ2 also induced apoptotic cell death in triple-negative, but not ER/PR+, breast cancer cells or normal human cells. Meanwhile, THZ2 did not elicit an obvious alteration in cell cycle. |
| Animal experiment [2]: | |
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Animal models |
Nude mice bearing triple-negative breast tumors |
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Dosage form |
10 mg/kg; i.p.; 50 hrs or 25 days |
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Applications |
In nude mice bearing triple-negative breast tumors, THZ2 significantly reduced the growth rate of tumors without affecting body weight. Moreover, both acute (50 hrs) and chronic exposure (25 days) to THZ2 substantially reduced CTD phosphorylation of RNAPII at all 3 phosphorylation sites (i.e. S2, S5 and S7), which indicated that CDK7 was efficiently inhibited in the tumor cells. According to the immunostaining analysis results of tumor tissues isolated from mice treated with THZ2, reduced proliferation and increased apoptosis were observed. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Wang Y, Zhang T, Kwiatkowski N et al. CDK7-dependent transcriptional addiction in triple-negative breast cancer. Cell. 2015 Sep 24;163(1):174-86. | |
| Cas No. | 1604810-84-5 | SDF | |
| 化学名 | (Z)-N-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-3-((Z)-((E)-4-(dimethylamino)-1-hydroxybut-2-en-1-ylidene)amino)benzimidic acid | ||
| Canonical SMILES | CN(C/C([H])=C([H])/C(O)=N/C1=CC=CC(/C(O)=N/C2=CC(NC3=NC=C(Cl)C(C4=CNC5=CC=CC=C45)=N3)=CC=C2)=C1)C | ||
| 分子式 | C31H28ClN7O2 | 分子量 | 566.05 |
| 溶解度 | ≥ 28.3mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
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 |
| 10 mM | 0.1767 mL | 0.8833 mL | 1.7666 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet