Advances in developing noncovalent small molecules targeting Keap1.
Drug Discov Today
; 28(12): 103800, 2023 Dec.
Article
in En
| MEDLINE
| ID: mdl-37852355
ABSTRACT
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 on their pharmacological effects, to examine the therapeutic potential for this compound class.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxidative Stress
/
NF-E2-Related Factor 2
Language:
En
Journal:
Drug Discov Today
Year:
2023
Document type:
Article