Development and Therapeutic Potential of NUAKs Inhibitors

NUAK isoforms, NUAK1 (ARK5) and NUAK2 (SNARK), are important members of the AMPK family of protein kinases. They are involved in a broad spectrum of physiological and cellular events, and sometimes their biological roles overlap. NUAK isoform dysregulation is associated with numerous pathological di...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2021-01, Vol.64 (1), p.2-25
Main Authors: Faisal, Muhammad, Kim, Jae Ho, Yoo, Kyung Ho, Roh, Eun Joo, Hong, Soon Sun, Lee, So Ha
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Apoptosis
Cell Survival
Disease Progression
Homeostasis
Humans
Isoenzymes - metabolism
Mice
Mice, Knockout
Protein Kinase Inhibitors - chemistry
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Protein Kinases - metabolism
Quality of Life
Sequence Homology, Amino Acid
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Summary:NUAK isoforms, NUAK1 (ARK5) and NUAK2 (SNARK), are important members of the AMPK family of protein kinases. They are involved in a broad spectrum of physiological and cellular events, and sometimes their biological roles overlap. NUAK isoform dysregulation is associated with numerous pathological disorders, including neurodegeneration, metastatic cancer, and diabetes. Therefore, they are promising therapeutic targets in metabolic diseases and cancers; consequently, various NUAK-targeted inhibitors have been disclosed. The first part of this review comprises a brief discussion of the homology, expression, structure, and characteristics of NUAK isoforms. The second part focuses on NUAK isoforms' involvement in crucial biological operations, including mechanistic findings, highlighting how their abnormal functioning contributes to disease progression and quality of life. The third part summarizes the key findings and applications of targeting NUAK isoforms for treating multiple cancers and neurodegenerative disorders. The final part systematically presents a critical review and analysis of the literature on NUAK isoform inhibitions through small molecules.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.0c00533