CCT251545
目录号 : GC17606
An orally bioavailable inhibitor of Wnt signaling
Cas No.:1661839-45-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
APC mutant human colorectal cancer cell line (COLO205-F1756 clone 4) |
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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 |
0.035 μM |
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Applications |
In COLO205-F1756 clone 4, CCT251545 potently inhibited WNT pathway activity, with the IC50 value of 0.035 μM. Moreover, CCT251545 did not affect endogenous levels of TCF1 or TCF4. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing COLO205-F1756 clone 4 xenografts |
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Dosage form |
70 mg/kg; p.o.; b.i.d., for 9 days |
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Applications |
In mice bearing COLO205-F1756 clone 4 xenografts, CCT251545 (70 mg/kg; p.o.; b.i.d., for 9 days) substantially inhibited WNT signaling and reduced tumor weights by 37.5%. |
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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, Crumpler S, Pichowicz M, et al. Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen. J Med Chem, 2015, 58(4): 1717-1735. | |
CCT251545 is an orally bioavailable and potent inhibitor of WNT signaling with IC50 value of 5 nM [1].
The WNT signaling network controls cellular functions such as proliferation and differentiation, and is a major regulator of mammalian development. WNT signaling is frequently deregulated in malignancy, especially in colon cancer, and plays an important role in the generation and maintenance of cancer stem cells [1].
CCT251545 is an orally bioavailable and potent WNT signaling inhibitor discovered through high-throughput cell-based screening. CCT251545 is also a potent and selective chemical probe for the human Mediator complex-associated protein kinases CDK8 and CDK19. CCT251545 changed gene expression regulated by WNT pathway and other on-target effects of modulating CDK8 and CDK19, including expression of genes regulated by STAT1 [2]. CCT251545 also inhibited GSK3α and -β with IC50 values of 0.462 and 0.690 μM. In APC mutant human colorectal cancer cell line (COLO205-F1756 clone 4), CCT251545 inhibited WNT pathway activity with IC50 value of 0.035 nM [1].
In both mouse and rat, CCT251545 exhibited moderate clearance with moderate to high oral bioavailability. In mice bearing COLO205-F1756 clone 4 tumor xenografts, CCT251545 (70 mg/kg po bid for 9 days) significantly inhibited WNT signaling and reduced tumor weights by 37.5% [1].
References:
[1]. Mallinger A, Crumpler S, Pichowicz M, et al. Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen. J Med Chem, 2015, 58(4): 1717-1735.
[2]. Dale T, Clarke PA, Esdar C, et al. A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. Nat Chem Biol, 2015, 11(12): 973-980.
| Cas No. | 1661839-45-7 | SDF | |
| 化学名 | 8-(3-chloro-5-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decan-1-one | ||
| Canonical SMILES | O=C(NCC1)C1(CC2)CCN2C3=C(C4=CC=C(C5=CN(C)N=C5)C=C4)C=NC=C3Cl | ||
| 分子式 | C23H24ClN5O | 分子量 | 421.92 |
| 溶解度 | ≥ 42.2mg/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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3701 mL | 11.8506 mL | 23.7012 mL |
| 5 mM | 0.474 mL | 2.3701 mL | 4.7402 mL |
| 10 mM | 0.237 mL | 1.1851 mL | 2.3701 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。