@article{APS9729,
author = {Mao-rong ZHU and Dao-hai DU and Jun-chi HU and Lian-chun LI and Jing-qiu LIU and Hong DING and Xiang-qian KONG and Hua-liang JIANG and Kai-xian CHEN and Cheng LUO},
title = {Development of a high-throughput fluorescence polarization assay for the discovery of EZH2-EED interaction inhibitors},
journal = {Acta Pharmacologica Sinica},
volume = {39},
number = {2},
year = {2018},
keywords = {},
abstract = {Abstract
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.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9729}
}