Advances in developing noncovalent small molecules targeting Keap1
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Kelch-like ECH-associated protein 1 (Keap1) is a drug target for diseases involving oxidative stress and inflammation. There are three covalent Keap1-binding drugs on the market, but noncovalent compounds that inhibit the interaction between Keap1 and nuclear factor erythroid 2-related factor 2 (Nrf2) represent an attractive alternative. Both compound types prevent degradation of Nrf2, leading to the expression of antioxidant and antiinflammatory proteins. However, their off-target profiles differ as do their exact pharmacodynamic effects. Here, we discuss the opportunities and challenges of targeting Keap1 with covalent versus noncovalent inhibitors. We then provide a comprehensive overview of current noncovalent Keap1-Nrf2 inhibitors, with a focus their on pharmacological effects, to examine the therapeutic potential for this compound class.
Original language | English |
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Article number | 103800 |
Journal | Drug Discovery Today |
Volume | 28 |
Issue number | 12 |
Number of pages | 25 |
ISSN | 1359-6446 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
ID: 370663219