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Int J Mol Sci. 2019 Sep 10;20(18). pii: E4445. doi: 10.3390/ijms20184445.

Emerging Screening Approaches in the Development of Nrf2-Keap1 Protein-Protein Interaction Inhibitors.

Author information

1
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. duncanleung@um.edu.mo.
2
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. mb75834@connect.um.edu.mo.
3
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. yb67509@umac.mo.
4
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong 999077, China. yjhxliuhao@163.com.
5
College of International Education, School of Continuing Education, Hong Kong Baptist University, Shek Mun, Hong Kong 999077, China. simonhan@hkbu.edu.hk.
6
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong 999077, China. edmondma@hkbu.edu.hk.

Abstract

Due to role of the Keap1-Nrf2 protein-protein interaction (PPI) in protecting cells from oxidative stress, the development of small molecule inhibitors that inhibit this interaction has arisen as a viable approach to combat maladies caused by oxidative stress, such as cancers, neurodegenerative disease and diabetes. To obtain specific and genuine Keap1-Nrf2 inhibitors, many efforts have been made towards developing new screening approaches. However, there is no inhibitor for this target entering the clinic for the treatment of human diseases. New strategies to identify novel bioactive compounds from large molecular databases and accelerate the developmental process of the clinical application of Keap1-Nrf2 protein-protein interaction inhibitors are greatly needed. In this review, we have summarized virtual screening and other methods for discovering new lead compounds against the Keap1-Nrf2 protein-protein interaction. We also discuss the advantages and limitations of different strategies, and the potential of this PPI as a drug target in disease therapy.

KEYWORDS:

Keap1–Nrf2; inhibitors; oxidative stress; protein–protein interaction; virtual screening

PMID:
31509940
DOI:
10.3390/ijms20184445
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