Development and Therapeutic Potential of NUAKs Inhibitors
Development and Therapeutic Potential of NUAKs Inhibitors
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DOI：
10.1021/acs.jmedchem.0c00533
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发表时间：
2021-01-14
影响因子：
7.3
通讯作者：
Lee, So Ha
中科院分区：
文献类型：
--
作者：
Faisal, Muhammad;Kim, Jae Ho;Lee, So Ha
NUAK亚型NUAK 1（ARK 5）和NUAK 2（SNARK）是AMPK蛋白激酶家族的重要成员。它们参与广泛的生理和细胞事件，有时它们的生物学作用会重叠。NUAK同种型失调与许多病理性疾病相关，包括神经变性、转移性癌症和糖尿病。因此，它们是代谢疾病和癌症中有希望的治疗靶标;因此，已经公开了各种NUAK靶向抑制剂。本文的第一部分包括一个简短的讨论NUAK亚型的同源性，表达，结构和特点。第二部分着重于NUAK亚型参与关键的生物学操作，包括机制发现，强调它们的异常功能如何有助于疾病进展和生活质量。第三部分总结了靶向NUAK亚型治疗多种癌症和神经退行性疾病的关键发现和应用。最后一部分系统地提出了一个批判性的审查和分析的文献NUAK异构体抑制通过小分子。
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.