developmentofahighthroughputfluorescencepolarizationassayforthediscoveryofezh2eedinteractioninhibitors

doi:10.1038/aps.2017.59

	developmentofahighthroughputfluorescencepolarizationassayforthediscoveryofezh2eedinteractioninhibitors
	Zhu Maorong 1; Du Daohai 2; Hu Junchi 2; Li Lianchun 2; Liu Jingqiu 2; Ding Hong 2; Kong Xiangqian 2; Jiang Hualiang 2; Chen Kaixian 2; Luo Cheng 2
刊名	actapharmacologicasinica
	2018
卷号	39 期号:2 页码:302
关键词	PRC2 EZH2 EED protein-protein interaction fluorescence polarization high-throughput screening apomorphine hydrochloride oxyphenbutazone nifedipine ergonovine maleate
ISSN号	1671-4083
DOI	10.1038/aps.2017.59
英文摘要	Aberrant activity of enhancer of zeste homolog 2 (EZH2) is associated with a wide range of human cancers. The interaction of EZH2 with embryonic ectoderm development (EED) is required for EZH2's catalytic activity. Inhibition of the EZH2-EED complex thus represents a novel strategy for interfering with the oncogenic potentials of EZH2 by targeting both its catalytic and non-catalytic functions. To date, there have been no reported high-throughput screening (HTS) assays for inhibitors acting at the EZH2-EED interface. In this study, we developed a fluorescence polarization (FP)-based HTS system for the discovery of EZH2-EED interaction inhibitors. The tracer peptide sequences, positions of fluorescein labeling,and a variety of physicochemical conditions were optimized. The high Z' factors (>0.9) at a variety of DMSO concentrations suggested that this system is robust and suitable for HTS. The minimal sequence requirement for the EZH2-EED interaction was determined by using this system. A pilot screening of an in-house compound library containing 1600 FDA-approved drugs identified four compounds (apomorphine hydrochloride, oxyphenbutazone, nifedipine and ergonovine maleate) as potential EZH2-EED interaction inhibitors.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288333]
专题	中国科学院上海药物研究所
作者单位	1.中国科学技术大学 2.中国科学院上海药物研究所
推荐引用方式 GB/T 7714	Zhu Maorong,Du Daohai,Hu Junchi,et al. developmentofahighthroughputfluorescencepolarizationassayforthediscoveryofezh2eedinteractioninhibitors[J]. actapharmacologicasinica,2018,39(2):302.
APA	Zhu Maorong.,Du Daohai.,Hu Junchi.,Li Lianchun.,Liu Jingqiu.,...&Luo Cheng.(2018).developmentofahighthroughputfluorescencepolarizationassayforthediscoveryofezh2eedinteractioninhibitors.actapharmacologicasinica,39(2),302.
MLA	Zhu Maorong,et al."developmentofahighthroughputfluorescencepolarizationassayforthediscoveryofezh2eedinteractioninhibitors".actapharmacologicasinica 39.2(2018):302.