Discovery of Novel Polo-Like Kinase 1 Polo-Box Domain Inhibitors to   Induce Mitotic Arrest in Tumor Cells

doi:10.1021/acs.jmedchem.6b00261

CORC > 北京大学 > 化学与分子工程学院

	Discovery of Novel Polo-Like Kinase 1 Polo-Box Domain Inhibitors to Induce Mitotic Arrest in Tumor Cells
	Qin, Tan ; Chen, Fangjin ; Zhuo, Xiaolong ; Guo, Xiao ; Yun, Taikangxiang ; Liu, Ying ; Zhang, Chuanmao ; Lai, Luhua
刊名	JOURNAL OF MEDICINAL CHEMISTRY
	2016
关键词	ADVANCED SOLID MALIGNANCIES GROWTH IN-VIVO PHASE-I CELLULAR UPTAKE PLK1 POLO-LIKE-KINASE-1 CANCER PHOSPHOPEPTIDES IDENTIFICATION RECOGNITION
DOI	10.1021/acs.jmedchem.6b00261
英文摘要	Polo-like kinase 1(Plk1) is vital for cell mitosis and has been identified as anticancer target. Its polo-box domain (PBD) mediates substrate binding, blocking of which may offer selective Plk1 inhibition compared to kinase domain inhibitors. Although several PBD inhibitors were reported, most of them suffer from low cell activity. Here, we report the discovery of novel inhibitors to induce mitotic arrest in HeLa cells by virtual screening with Plk1 PBD and cellular activity testing. Of the 81 compounds tested in the cell assay, 10 molecules with diverse chemical scaffolds are potent to induce mitotic arrest of HeLa at low micromolar concentrations. The best compound induces mitotic arrest of HeLa cells with an EC50 of 4.4 mu M. The cellular active inhibitors showed binding to Plk1 PBD and compete with PBD substrate in microscale thermophoresis analysis.; Ministry of Science and Technology of China [2015CB910300, 2016YFA0502303]; National Natural Science Foundation of China [31430051, 91313302]; SCI(E); PubMed; ARTICLE; zhangcm@pku.edu.cn; lhlai@pku.edu.cn; 15; 7089-7096; 59
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/491612]
专题	化学与分子工程学院生命科学学院
推荐引用方式 GB/T 7714	Qin, Tan,Chen, Fangjin,Zhuo, Xiaolong,et al. Discovery of Novel Polo-Like Kinase 1 Polo-Box Domain Inhibitors to Induce Mitotic Arrest in Tumor Cells[J]. JOURNAL OF MEDICINAL CHEMISTRY,2016.
APA	Qin, Tan.,Chen, Fangjin.,Zhuo, Xiaolong.,Guo, Xiao.,Yun, Taikangxiang.,...&Lai, Luhua.(2016).Discovery of Novel Polo-Like Kinase 1 Polo-Box Domain Inhibitors to Induce Mitotic Arrest in Tumor Cells.JOURNAL OF MEDICINAL CHEMISTRY.
MLA	Qin, Tan,et al."Discovery of Novel Polo-Like Kinase 1 Polo-Box Domain Inhibitors to Induce Mitotic Arrest in Tumor Cells".JOURNAL OF MEDICINAL CHEMISTRY (2016).