Rapid identification of Keap1-Nrf2 small-molecule inhibitors through structure-based virtual screening and hit-based substructure search

Chunlin Zhuang, Sreekanth Narayanapillai, Wannian Zhang, Yuk Yin Sham, Chengguo Xing

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1121-1126
Number of pages6
JournalJournal of medicinal chemistry
Volume57
Issue number3
DOIs
StatePublished - Feb 13 2014

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