Targeting kelch-like (KLHL) proteins: achievements, challenges and perspectives.

Yangguo Zhou, Qiong Zhang, Ziquan Zhao, Xiuqi Hu, Qidong You, Zhengyu Jiang

European journal of medicinal chemistry 2024 Apr 05

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Kelch-like proteins (KLHLs) are a large family of BTB-containing proteins. KLHLs function as the substrate adaptor of Cullin 3-RING ligases (CRL3) to recognize substrates. KLHLs play pivotal roles in regulating various physiological and pathological processes by modulating the ubiquitination of their respective substrates. Mounting evidence indicates that mutations or abnormal expression of KLHLs are associated with various human diseases. Targeting KLHLs is a viable strategy for deciphering the KLHLs-related pathways and devising therapies for associated diseases. Here, we comprehensively review the known KLHLs inhibitors to date and the brilliant ideas underlying their development. Copyright © 2024 Elsevier Masson SAS. All rights reserved.

Citation

Yangguo Zhou, Qiong Zhang, Ziquan Zhao, Xiuqi Hu, Qidong You, Zhengyu Jiang. Targeting kelch-like (KLHL) proteins: achievements, challenges and perspectives. European journal of medicinal chemistry. 2024 Apr 05;269:116270