Rapid Identification of Keap1-Nrf2 Small-Molecule Inhibitors through Structure-Based Virtual Screening and Hit-Based Substructure Search
Rapid Identification of Keap1-Nrf2 Small-Molecule Inhibitors through Structure-Based Virtual Screening and Hit-Based Substructure Search
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DOI：
10.1021/jm4017174
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发表时间：
2014-02-13
影响因子：
7.3
通讯作者：
Xing, Chengguo
中科院分区：
文献类型：
--
作者：
Zhuang, Chunlin;Narayanapillai, Sreekanth;Xing, Chengguo
在本研究中，利用基于快速结构的虚拟筛选和基于命中的子结构搜索来识别破坏Keap1-Nrf2相互作用的小分子。特别强调在经济地建立新型支架的信息结构活性关系（SAR）的同时，最大限度地探索初始命中的化学多样性。我们最有效的非共价抑制剂在Nrf2激活中表现出比迄今为止已知的最活跃的非共价Keap1抑制剂三倍的细胞活化能力。
In this study, rapid structure-based virtual screening and hit-based substructure search were utilized to identify small molecules that disrupt the interaction of Keap1-Nrf2. Special emphasis was placed toward maximizing the exploration of chemical diversity of the initial hits while economically establishing informative structure activity relationship (SAR) of novel scaffolds. Our most potent noncovalent inhibitor exhibits three times improved cellular activation in Nrf2 activation than the most active noncovalent Keap1 inhibitor known to date.