GSK-923295
(Synonyms: 3-氯-N-{(1S)-2-[(N,N-二甲基甘氨酰)氨基]-1-[(4-{8-[(1S)-1-羟基乙基]咪唑并[1,2-A]吡啶-2-基}苯基)甲基]乙基}-4-[(1-甲基乙基)氧基]苯甲酰胺,GSK 923295;GSK923295) 目录号 : GC15659
An inhibitor of CENP-E
Cas No.:1088965-37-0
Sample solution is provided at 25 µL, 10mM.
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GSK923295 is a specific inhibitor of CENP-E kinesin motor with IC50 value of 3.2 nM [1].
Centromere-associated protein E (CENP-E) is a mitotic kinesin, which is the connect of mitosis process with the mitotic checkpoint signaling. It Interacts with spindle microtubules and contribute to the chromosome alignment, and thus it regulates the cell-cycle transition from metaphase to anaphase.
When asynchronous cultured cells were exposed to GSK923295, the penetrant cell-cycle delay in mitosis was observed, which accompanied with morphological changes similar to RNAi-mediated knockdown of CENP-E mRNA. It indicated a significant inhibition of CENP-E by GSK923295. In the presence of GSK9232195, CENP-E microtubule (MT)-stimulated ATPase showed a dramatic slowing of release of ADP and Pi, where the ATP-bound form was stabilized and the activity of CENP-E was inhibited. This observation suggested GSK923295 inhibited CENP-E via the suppression of MT-stimulated ATPase [1].
In mouse model, mice bearing xenografts of the Colo205 colon tumor cell line were administered with GSK923295 of 125 mg/kg. The result showed GSK923295-induced cell-cycle changes of tumor cells and increased scattered apoptosis body. Additionally, long-term study via measuring tumor volume revealed significant antitumor activity of GSK923295, in a manner of dose-dependent [1].
Reference:
[1] Wood K W et al. , Antitumor activity of an allosteric inhibitor of centromere-associated protein-E. 2010, 107 (13): 5839-5844.
| Kinase experiment [1]: | |
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Enzymology |
Kinesin motor domains were expressed in Escherichia coli BL21 (DE3) and purified. CENP-E proteins included residues 2 ~ 340 with a carboxyl-terminal 6-his tag. All studies using MT were conducted in PEM25 buffer [25 mM PipesK+ (pH 6.8), 2 mM MgCl2, 1 mM EGTA] supplemented with 10 μM Paclitaxel. The IC50 for steady-state inhibition was determined at 500 μM ATP, 5 μM MT and 1 nM CENP-E in PEM25 buffer. |
| Cell experiment [1]: | |
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Cell lines |
Tumor cell lines |
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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℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
~ 10 μM; 72 hrs |
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Applications |
In 237 tumor cell lines, GSK92329 potently inhibited tumor cell growth, with an average GI50 of 253 nM and a median GI50 of 32 nM. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing Colo205 xenografts |
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Dosage form |
125 mg/kg; i.p.; 2 cycles of 3 daily injections separated by 1 week |
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Applications |
GSK923295 exhibited robust and dose-dependent antitumor activity against Colo205 xenografts, including partial and complete regressions at the dose of 125 mg. |
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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]. Wood K W et al. , Antitumor activity of an allosteric inhibitor of centromere-associated protein-E. 2010, 107 (13): 5839-5844. | |
| Cas No. | 1088965-37-0 | SDF | |
| 别名 | 3-氯-N-{(1S)-2-[(N,N-二甲基甘氨酰)氨基]-1-[(4-{8-[(1S)-1-羟基乙基]咪唑并[1,2-A]吡啶-2-基}苯基)甲基]乙基}-4-[(1-甲基乙基)氧基]苯甲酰胺,GSK 923295;GSK923295 | ||
| 化学名 | 3-chloro-N-[(2S)-1-[[2-(dimethylamino)acetyl]amino]-3-[4-[8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl]phenyl]propan-2-yl]-4-propan-2-yloxybenzamide | ||
| Canonical SMILES | CC(C)OC1=C(C=C(C=C1)C(=O)NC(CC2=CC=C(C=C2)C3=CN4C=CC=C(C4=N3)C(C)O)CNC(=O)CN(C)C)Cl | ||
| 分子式 | C32H38ClN5O4 | 分子量 | 592.14 |
| 溶解度 | ≥ 29.6mg/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 | 1.6888 mL | 8.4439 mL | 16.8879 mL |
| 5 mM | 0.3378 mL | 1.6888 mL | 3.3776 mL |
| 10 mM | 0.1689 mL | 0.8444 mL | 1.6888 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