切换导航

GSK461364

现货
Catalog No.
A8441
Plk1抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL Ethanol)
¥ 1,300.00
现货
10mg
¥ 1,500.00
现货
50mg
¥ 4,800.00
Ship with 10-15 days
500mg
¥ 18,000.00
Ship with 10-15 days

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

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.

文献引用

1. Velpurisiva P, Rai P. "Synergistic Action of Gefitinib and GSK41364A Simultaneously Loaded in Ratiometrically-Engineered Polymeric Nanoparticles for Glioblastoma Multiforme." J Clin Med. 2019 Mar 15;8(3). pii: E367. PMID:30875975
2. Velpurisiva P, Piel BP, et al. "GSK461364A, a Polo-Like Kinase-1 Inhibitor Encapsulated in Polymeric Nanoparticles for the Treatment of Glioblastoma Multiforme (GBM)." Bioengineering (Basel). 2018 Oct 9;5(4). pii: E83. PMID:30304810
3. Higuchi F, Fink AL, et al. "PLK1 inhibition targets Myc-activated malignant glioma cells irrespective of mismatch repair deficiency-mediated acquired resistance to temozolomide." Mol Cancer Ther. 2018 Sep 14. pii: molcanther.0177.2018. PMID:30217967

Chemical Properties

StorageStore at -20°C
M.Wt543.6
Cas No.929095-18-1
FormulaC27H28F3N5O2S
Solubility≥15.65mg/mL in Ethanol
Chemical Name5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide
SDFDownload SDF
Canonical SMILESCC(C1=CC=CC=C1C(F)(F)F)OC2=C(SC(=C2)N3C=NC4=C3C=C(C=C4)CN5CCN(CC5)C)C(=O)N
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

胶质母细胞瘤成人T98G细胞系和儿童SF188细胞系

溶解方法

在DMSO中的溶解度大于15.65 mg/mL。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

75,150和300 nM,72 h

应用

GSK461364处理72小时后,胶质瘤T98G细胞和SF188细胞的增殖显著降低。

临床实验[2]:

临床模型

18岁以上的确诊为晚期实体瘤的无有效治疗方法的患者

剂量

静脉输注,50mg一周一次或25mg每周两次,随着治疗提高剂量

应用

4小时输液结束后,GSK461364的血浆浓度呈双指数下降。GSK461364最初快速分布,血浆浓度在输注停止8小时内降至Cmax的约15%-20%。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

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.

生物活性

Description GSK461364是PIK1的抑制剂,其Ki值为2.2 nM。
靶点 PLK1          
IC50 2.2 nM(Ki)          

质量控制

化学结构

GSK461364

相关生物数据

GSK461364

相关生物数据

GSK461364

相关生物数据

GSK461364