KEAP1 is a BTB-Kelch family E3 ligase that ubiquitinates NRF2 to control oxidative cellular stress and is therefore an important therapeutic target. The Bullock group was happy to host PhD student Yuting Qin from the lab of Anders Bach (University of Copenhagen) as she visited CMD to complete her study of tetrahydroisoquinoline-based inhibitors of KEAP1. This series of compounds binds non-covalently to the Kelch domain of KEAP1 with potencies up to Ki = 13 nM. The work is now published in J Med Chem with the title “Structure-Guided Conformational Restriction Leading to High-Affinity, Selective, and Cell-Active Tetrahydroisoquinoline-Based Noncovalent Keap1-Nrf2 Inhibitors”.
