Design, Synthesis and Evaluation of Novel Small Molecules Acting As Keap1-Nrf2 Protein-protein Interaction Inhibitors

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2022 Sep 21

PMID 36128875

Authors

Yunfeng Sun

Lulu Zheng

Bo Yang

Shuyu Ge

Qiang Li

Mingwan Zhang

Shenghui Shen

Yin Ying

Affiliations

Soon will be listed here.

Abstract

Direct interference with Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 protein-protein interaction (PPI) has recently been introduced as an attractive approach to control life-threatening diseases like myocarditis. The present study aimed to investigate the potential application in myocarditis of a series of novel non-naphthalene derivatives as potential Keap1-Nrf2 PPI inhibitors. Our results indicated that the optimal compound displayed the highest metabolic stability and showed notable Keap1-Nrf2 PPI inhibitory activities . effectively triggered Nrf2 activation and increased the protein and mRNA expression of Nrf2-regulated genes in H9c2 cells. Moreover, pre-treatment with was shown to mitigate LPS-induced damage to H9c2 cells, causing a marked decrease in the levels of inflammatory factors as well as reactive oxygen species (ROS). Furthermore, was also shown to be non-mutagenic in the Ames test. Overall, our findings suggest that may be a promising drug lead as a Keap1-Nrf2 PPI inhibitor for myocarditis treatment.

Citing Articles

The role of Keap1-Nrf2 signaling pathway in the treatment of respiratory diseases and the research progress on targeted drugs.

Zhang M, Wang J, Liu R, Wang Q, Qin S, Chen Y Heliyon. 2024; 10(18):e37326.

PMID: 39309822 PMC: 11414506. DOI: 10.1016/j.heliyon.2024.e37326.

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