TY - JOUR AU - ZHU Mao-rong AU - DU Dao-hai AU - HU Jun-chi AU - LI Lian-chun AU - LIU Jing-qiu AU - DING Hong AU - KONG Xiang-qian AU - JIANG Hua-liang AU - CHEN Kai-xian AU - LUO Cheng PY - 2018 TI - Development of a high-throughput fluorescence polarization assay for the discovery of EZH2-EED interaction inhibitors JF - Acta Pharmacologica Sinica; Vol 39, No 2 (February 2018): Acta Pharmacologica Sinica Y2 - 2018 KW - N2 - 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. UR - http://www.chinaphar.com/article/view/9729