Advances in developing noncovalent small molecules targeting Keap1
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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Advances in developing noncovalent small molecules targeting Keap1. / Barreca, Marilia; Qin, Yuting; Hélène Cadot, Marie Elodie; Barraja, Paola; Bach, Anders.
I: Drug Discovery Today, Bind 28, Nr. 12, 103800, 2023.Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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TY - JOUR
T1 - Advances in developing noncovalent small molecules targeting Keap1
AU - Barreca, Marilia
AU - Qin, Yuting
AU - Hélène Cadot, Marie Elodie
AU - Barraja, Paola
AU - Bach, Anders
N1 - Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1016/j.drudis.2023.103800
DO - 10.1016/j.drudis.2023.103800
M3 - Review
C2 - 37852355
VL - 28
JO - Drug Discovery Today: BIOSILICO
JF - Drug Discovery Today: BIOSILICO
SN - 1359-6446
IS - 12
M1 - 103800
ER -
ID: 370663219