JNJ-7706621
(Synonyms: JNJ7706621, JNJ 7706621) 目录号 : GC12612
A dual inhibitor of CDKs and Aurora kinases
Cas No.:443797-96-4
Sample solution is provided at 25 µL, 10mM.
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JNJ-7706621 is a dual inhibitor of cyclin-dependent kinases (CDK) and Aurora kinases that potently inhibits CDK1, CDK2, CDK3, CDK4, CDK6, Aurora-A, and Aurora-B in vitro with 50% inhibition concentration IC50 values of 0.009, 0.004, 0.003, 0.058, 0.253, 0.175, 0.011 and 0.015 μmol/L respectively. JNJ-7706621 selectively inhibits proliferation of both normal human cells and tumor cells of various origins, where the efficacy of JNJ-7706621 is 10-fold greater in tumor cells (IC50 range of 0.112 to 0.514 μmol/L) than normal cells (IC50 range of 3.67 to 5.42 μmol/L). JNJ-7706621 has been found to induce apoptosis, suppress colony formation and inhibit cell growth regardless of p53, retinoblastoma or P-glycoprotein status in human cancer cells.
Reference
[1].Stuart Emanuel, Catherine A. Rugg, Robert H. Gruninger, Ronghui Lin, Angel Fuentes-Pesquera, Peter J. Connolly, Steven K. Wetter, Beth Hollister, Walter W. Kruger, Cheryl Napier, Linda Jolliffe, and Steven A. Middleton. The In vitro and In vivo Effects of JNJ-7706621: A Dual Inhibitor of Cyclin-Dependent Kinases and Aurora Kinases. Cancer Res 2005;65:9038-9046
| Kinase experiment [1]: | |
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In vitro kinase assay for CDK1 and Aurora kinases |
To identify compounds that inhibited CDK1 kinase activity, a screening method was developed using the CDK1/cyclin B complex purified from baculovirus to phosphorylate a biotinylated peptide substrate containing the consensus phosphorylation site for histone H1, which is phosphorylated in vivo by CDK1. Inhibition of CDK1 activity was measured by observing a reduced amount of 33P-γ-ATP incorporation into the immobilized substrate in streptavidin-coated 96-well scintillating microplates. CDK1 enzyme was diluted in 50 mM Tris-HCl (pH 8), 10 mM MgCl2, 0.1 mM Na3VO4, 1 mM DTT, 1% DMSO, 0.25 μM peptide, 0.1 μCi per well 33P-γ-ATP, and 5 μM ATP in the presence or absence of various concentrations of JNJ-7706621 and incubated at 30 °C for 1 hr. The reaction was terminated by washing with PBS containing 100 mM EDTA and plates were counted in a scintillation counter. Linear regression analysis of the percent inhibition by JNJ-7706621 was used to determine IC50 values. |
| Cell experiment [1]: | |
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Cell lines |
U937 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. 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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Reaction Conditions |
0, 0.5, 1, 2, 3 or 4 μM; 24 hrs |
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Applications |
In U937 cells, JNJ-7706621 time- and dose-dependently induced cell apoptosis. |
| Animal experiment [1]: | |
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Animal models |
Mouse xenograft model of A375 melanoma human tumor |
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Dosage form |
100 or 125 mg/kg; p.o. or i.p. |
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Applications |
In mouse xenograft model of A375 melanoma human tumor, JNJ-7706621 at the dose of 100 or 125 mg/kg caused tumor regression. |
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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]. Stuart Emanuel, Catherine A. Rugg, Robert H. Gruninger, Ronghui Lin, Angel Fuentes-Pesquera, Peter J. Connolly, Steven K. Wetter, Beth Hollister, Walter W. Kruger, Cheryl Napier, Linda Jolliffe, and Steven A. Middleton. The In vitro and In vivo Effects of JNJ-7706621: A Dual Inhibitor of Cyclin-Dependent Kinases and Aurora Kinases. Cancer Res 2005;65:9038-9046. | |
| Cas No. | 443797-96-4 | SDF | |
| 别名 | JNJ7706621, JNJ 7706621 | ||
| 化学名 | 4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide | ||
| Canonical SMILES | C1=CC(=C(C(=C1)F)C(=O)N2C(=NC(=N2)NC3=CC=C(C=C3)S(=O)(=O)N)N)F | ||
| 分子式 | C15H12F2N6O3S | 分子量 | 394.36 |
| 溶解度 | ≥ 19.7 mg/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 | 2.5358 mL | 12.6788 mL | 25.3575 mL |
| 5 mM | 0.5072 mL | 2.5358 mL | 5.0715 mL |
| 10 mM | 0.2536 mL | 1.2679 mL | 2.5358 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