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Published on: July 17, 2020
Targeting spleen tyrosine kinase (SYK): structure, mechanisms and drug discovery
Shuangqian Zhang1, Lilin Wang2, Yingying Lu1
1Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Abstract:
Spleen tyrosine kinase (SYK) is a crucial non-receptor tyrosine kinase involved in signaling pathways that regulate various cellular processes. It is primarily expressed in hematopoietic cells and myeloid cells, which are crucial for B-cell development, maturation and antibody production, and it is a key therapeutic target for autoimmune and allergic diseases. Overexpression of SYK is also associated with cancer and cardiovascular, cerebrovascular and neurodegenerative diseases, contributing to their initiation and progression. SYK is a promising target for drug development, and several inhibitors have already been reported. This review covers the structure and regulatory pathways of SYK, as well as its links to various diseases. It also highlights key small-molecule SYK inhibitors, their design strategies and their potential therapeutic benefits, aiming to enhance our understanding and aid in the discovery of more-effective SYK inhibitors.
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