CFI-400945
目录号 : GC13606
orally available, selective inhibitor of polo-like kinase 4 (PLK4)
Cas No.:1338800-06-8
Sample solution is provided at 25 µL, 10mM.
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CFI-400945 is an orally active, potent and selective inhibitor of polo-like kinase 4.
Polo-like kinase 4 (PLK4), a unique member of the Polo-like family of kinases, shares little homology with other polo-like kinases. PLK4 plays an essential role in centriole duplication. Overexpression of PLK4 overrides the centriole licensing mechanism and results in centriole amplification with multiple procentrioles forming around each parental centriole. Depletion of PLK4 by RNAi prevents the formation of abnormal centrioles and microtubule-based structures, causing mitotic defects and in some cell lines it can induce apoptosis [2].
In an assay using recombinant human PLK4, CFI-400945 inhibited PLK4 with an IC50 value of 2.8 ± 1.4 nM in an ATP competitive manner with a Ki value of 0.26 ± 0.1 nM. CFI-400945 inhibited autophosphorylation of PLK4 at serine 305 with an EC50 value of 12.3 nM in cells overexpressing PLK4 [1]. CFI-400945 showed no significant inhibitory activity against other PLK family members (PLK1, PLK2, and PLK3 with the IC50s of > 50 μM. In transfected HCT116 cells with TRKA, TRKB, and Tie2/TEK, the EC50 values were 84 nM, 88 nM, and 117 nM, respectively. CFI-400945 inhibited the activity of AURKA and AURKB with the EC50 value of 510 nM and 102 nM. CFI-400945 (≥ 200 nM) decreased the mean centriole number in asynchronous U2OS cells [1]. CFI-400945 inhibited a panel of breast cancer cell growth with the GI50 of 14-165 nM. In mice, the maximum tolerated dose (MTD) of CFI-400945 for once-daily oral administration was estimated to be 7.5-9.5 mg/kg [1].
References:
[1] Mason J M, Lin D C C, Wei X, et al. Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent[J]. Cancer Cell, 2014, 26(2): 163-176.
[2] Sillibourne J E, Bornens M. Polo-like kinase 4: the odd one out of the family[J]. Cell division, 2010, 5(1): 25.
| Cas No. | 1338800-06-8 | SDF | |
| 化学名 | (1S,2R)-2-[3-[(1E)-2-[4-[[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl]phenyl]ethenyl]-1H-indazol-6-yl]-5'-methoxy-spiro[cyclopropane-1,3'-[3H]indol]-2'(1'H)-one | ||
| Canonical SMILES | C[C@@H]1O[C@H](C)CN(CC2=CC=C(/C=C/C3=NNC4=C3C=CC([C@H]5[C@@]6(C(C=C(OC)C=C7)=C7NC6=O)C5)=C4)C=C2)C1 | ||
| 分子式 | C33H34N4O3 | 分子量 | 534.7 |
| 溶解度 | ≤12mg/ml in ethanol;10mg/ml in DMSO;20mg/ml in dimethyl formamide | 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 | 1.8702 mL | 9.351 mL | 18.7021 mL |
| 5 mM | 0.374 mL | 1.8702 mL | 3.7404 mL |
| 10 mM | 0.187 mL | 0.9351 mL | 1.8702 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