Targeting spleen tyrosine kinase (SYK): structure, mechanisms and drug discovery.

Autor: Zhang S; Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China., Wang L; Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China; Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China., Lu Y; Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China., Guo C; Nucleic Acid Division, Shanghai Cell Therapy Group, Shanghai 201805, China. Electronic address: guocx@shcell.com., Zhang T; Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China; The Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu 610031, China. Electronic address: 163zttong@163.com., Zhang L; Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China. Electronic address: zhanglanx_9@126.com.
Jazyk: angličtina
Zdroj: Drug discovery today [Drug Discov Today] 2024 Dec 07; Vol. 30 (1), pp. 104257. Date of Electronic Publication: 2024 Dec 07.
DOI: 10.1016/j.drudis.2024.104257
Abstrakt: 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.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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