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 language | English (US) |
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Pages (from-to) | 1121-1126 |
Number of pages | 6 |
Journal | Journal of medicinal chemistry |
Volume | 57 |
Issue number | 3 |
DOIs | |
State | Published - Feb 13 2014 |