GSK461364
(Synonyms: GSK461364A) 目录号 : GC12335
A reversible inhibitor of Plk1
Cas No.:929095-18-1
Sample solution is provided at 25 µL, 10mM.
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GSK461364 is a potent and reversible ATP competitive Plk1 inhibitor. Polo-like kinases (Plk) are a family of serine threonine kinases that are critical regulators of DNA damage response and cell cycle progression.
In vitro: GSK461364 showed at least 390-fold greater selectivity for Plk1 than for Plk2 and Plk3 and 1,000-fold greater than for 48 other kinases. The drug showed antiproliferative activity against multiple (>120) tumor cell lines and potently inhibited the proliferation of greater than 83% and 91% of these cell lines [1].
In vivo: Intraperitoneal administration of GSK461364 caused regression or tumor growth delay in different xenograft models. In vivo suppression of Plk1 by using GSK461364 resulted in mitotic arrest with aberrant mitotic figures consisting of monopolar or collapsed mitotic spindles [1].
Clinical trial: The final recommended phase II dose for GSK461364 was 225 mg administered intravenously. Moreover, GSK461364 was suggested to involve coadministration of prophylactic anticoagulation for further clinical evaluation [1].
Reference:
[1] Olmos D, Barker D, Sharma R, Brunetto AT, Yap TA, Taegtmeyer AB, Barriuso J, Medani H, Degenhardt YY, Allred AJ, Smith DA, Murray SC, Lampkin TA, Dar MM, Wilson R, de Bono JS, Blagden SP. Phase I study of GSK461364, a specific and competitive Polo-like kinase 1 inhibitor, in patients with advanced solid malignancies. Clin Cancer Res. 2011 May 15;17(10):3420-30.
| Cell experiment [1]: | |
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Cell lines |
Human adult glioblastoma T98G cell lines and pediatric SF188 cell lines |
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Preparation method |
The solubility of this compound in DMSO is > 15.65 mg/mL. 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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Reacting condition |
75, 150 and 300 nM, 72 h, |
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Applications |
After 72 h treatment, GSK461364 caused a significant decrease of proliferation in GBM T98G cells and SF188 cells. |
| Clinical experiment [2]: | |
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Animal models |
18 years or older patients with a confirmed diagnosis of advanced solid tumor for which no effective treatment was available. |
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Dosage form |
Intravenous infusion, 50 mg, once a week or 25 mg, twice a week, dose was escalated with treatment |
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Application |
After the end of the 4-hour infusion, GSK461364 plasma concentrations declined bi-exponentially. Distribution of GSK461364 was initially rapid and plasma concentrations decreased to approximately 15% to 20% of the Cmax within 8 hours of cessation of infusion. |
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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]. Pezuk J A, Brassesco M S, Morales A G, et al. Polo-like kinase 1 inhibition causes decreased proliferation by cell cycle arrest, leading to cell death in glioblastoma[J]. Cancer gene therapy, 2013, 20(9): 499-506. [2]. Olmos D, Barker D, Sharma R, et al. Phase I study of GSK461364, a specific and competitive Polo-like kinase 1 inhibitor, in patients with advanced solid malignancies[J]. Clinical Cancer Research, 2011, 17(10): 3420-3430. | |
| Cas No. | 929095-18-1 | SDF | |
| 别名 | GSK461364A | ||
| 化学名 | 5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide | ||
| Canonical SMILES | CC(C1=CC=CC=C1C(F)(F)F)OC2=C(SC(=C2)N3C=NC4=C3C=C(C=C4)CN5CCN(CC5)C)C(=O)N | ||
| 分子式 | C27H28F3N5O2S | 分子量 | 543.6 |
| 溶解度 | ≥ 15.65mg/mL in Ethanol | 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.8396 mL | 9.1979 mL | 18.3959 mL |
| 5 mM | 0.3679 mL | 1.8396 mL | 3.6792 mL |
| 10 mM | 0.184 mL | 0.9198 mL | 1.8396 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