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.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Zhu MR,Du DH,Hu JC,Li LC,Liu JQ,Ding H,Kong XQ,Jiang HL,Chen KX,Luo Cdoi
10.1038/aps.2017.59subject
Has Abstractpub_date
2018-02-01 00:00:00pages
302-310issue
2eissn
1671-4083issn
1745-7254pii
aps201759journal_volume
39pub_type
杂志文章abstract:AIM:Ischemia/reperfusion is an initial triggering event that leads to gut-induced acute lung injury (ALI). In this study, we investigated whether hypoxia inducible factor-1α (HIF-1α) played a role in the pathogenesis of lung injury induced by trauma and hemorrhagic shock (T/HS). METHODS:Male Wistar rats underwent lapa...
journal_title:Acta pharmacologica Sinica
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abstract:AIM:The aim of this study was to evaluate the relative contributions of the ipsilateral and contralateral cerebellum to the acquisition of unilateral classical eyeblink conditioning (EBCC). METHODS:The unilateral EBCC was achieved using a binaural tone conditioned stimulus (CS) paired with a left airpuff unconditioned...
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pub_type: 杂志文章,评审
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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journal_title:Acta pharmacologica Sinica
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doi:
更新日期:2001-07-01 00:00:00
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更新日期:2020-01-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2016.134
更新日期:2017-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/aps.2016.72
更新日期:2016-09-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2011.86
更新日期:2011-09-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00162.x
更新日期:2005-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/s41401-020-0460-0
更新日期:2020-07-09 00:00:00
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pub_type: 杂志文章
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更新日期:2012-10-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1038/aps.2017.195
更新日期:2018-05-01 00:00:00
abstract:AIM:To simultaneously investigate the contribution of the alpha 1 chain of collagen type 1 (COL1A1) and alpha2-HS-glycoprotein (AHSG) genes to the variation of bone geometric parameters in both Caucasians and Chinese. METHODS:Six hundred and five Caucasian individuals from 157 nuclear families and 1228 Chinese subject...
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pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00522.x
更新日期:2007-03-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00306.x
更新日期:2006-05-01 00:00:00
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更新日期:2008-03-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2013.200
更新日期:2014-05-01 00:00:00
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doi:
更新日期:2003-08-01 00:00:00
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doi:
更新日期:2000-09-01 00:00:00
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journal_title:Acta pharmacologica Sinica
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doi:
更新日期:2003-09-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00294.x
更新日期:2006-04-01 00:00:00
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doi:
更新日期:2004-04-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.96
更新日期:2013-12-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.88
更新日期:2016-12-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00331.x
更新日期:2006-08-01 00:00:00