CCT251545 analogue, Compound 51
目录号 : GC18051
Potent, Selective, orally bioavailable CDK 8/19 Inhibitor
Sample solution is provided at 25 µL, 10mM.
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CCT251545 analogue, Compound 51 is a potent and selective CDK8/19 inhibitor with IC50 values of 5.1 nM and 5.6 nM, respectively [1].
Mediator complex-associated kinases CDK8 and CDK19 are involved in the regulation of multiple transcription pathways. CDK8 plays as an oncogene in gastric and colorectal cancers through activation of WNT signaling [1].
CCT251545 analogue, Compound 51 is a potent and selective CDK8/19 inhibitor. In SW620 human colorectal carcinoma cells harbouring activating APC-mutation, Compound 51 inhibited phospho-STAT1SER727 with IC50 value of 17.9 nM, a biomarker of CDK8 inhibition [1].
In vivo mouse and rat PK experiments, Compound 51 demonstrated medium in vivo clearance and Vd but low bioavailability in mice. In a SW620 colorectal carcinoma human tumor xenograft model, Compound 51 (5 mg/kg po dose) inhibited phospho-STAT1SER727 in a time-dependent way. Compound 51 is an advanced chemical tool to further explore the efficacy, safety and tolerability of dual CDK8/19 ligands [1].
Reference:
[1].Mallinger A, Schiemann K, Rink C, et al. 2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19. ACS Med Chem Lett. 2016 Mar 28;7(6):573-8.
| Cell experiment [1]: | |
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Cell lines |
SW620 cells |
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Preparation method |
This compound is soluble in DMSO. 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 |
N/A |
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Applications |
In human colorectal carcinoma SW620 cells harboring an activating APC-mutation, CCT251545 analogue, Compound 51 potently inhibited phospho-STAT1SER727. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing human colorectal carcinoma SW620 cells |
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Dosage form |
5 mg/kg; p.o.; b.i.d. |
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Applications |
In mice bearing human colorectal carcinoma SW620 cells, CCT251545 analogue, Compound 51, reduced phospho-STAT1SER727 level in a time-dependent manner. At the dose of 5 mg/kg, a b.i.d. schedule would be required in order to achieve the maximal inhibitory effect. |
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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]. Mallinger A, Schiemann K, Rink C, et al. 2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19. ACS Med Chem Lett. 2016 Mar 28;7(6):573-8. | |
| Cas No. | N/A | SDF | |
| 化学名 | (5-amino-8-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)-1,6-naphthyridin-2-yl)(3-methoxyazetidin-1-yl)methanone | ||
| Canonical SMILES | NC1=C2C(N=C(C(N3CC(OC)C3)=O)C=C2)=C(C4=CC=C(C5=CN(C)N=C5)C=C4)C=N1 | ||
| 分子式 | C23H22N6O2 | 分子量 | 414.46 |
| 溶解度 | ≥ 20.7mg/mL in DMSO with gentle warming | 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4128 mL | 12.0639 mL | 24.1278 mL |
| 5 mM | 0.4826 mL | 2.4128 mL | 4.8256 mL |
| 10 mM | 0.2413 mL | 1.2064 mL | 2.4128 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet