Zhang Shuangqian, Wang Lilin, Lu Yingying, Guo Chuanxin, Zhang Tongtong, Zhang Lan
Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
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.
Drug Discov Today. 2025 Jan;30(1):104257. doi: 10.1016/j.drudis.2024.104257. Epub 2024 Dec 7.
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.
脾酪氨酸激酶（SYK）是一种关键的非受体酪氨酸激酶，参与调节各种细胞过程的信号通路。它主要在造血细胞和髓细胞中表达，这些细胞对B细胞的发育、成熟和抗体产生至关重要，并且它是自身免疫性疾病和过敏性疾病的关键治疗靶点。SYK的过表达还与癌症以及心血管、脑血管和神经退行性疾病相关，促进这些疾病的发生和发展。SYK是药物开发的一个有前景的靶点，并且已经报道了几种抑制剂。本综述涵盖了SYK的结构和调节途径，以及它与各种疾病的联系。它还重点介绍了关键的小分子SYK抑制剂、它们的设计策略及其潜在的治疗益处，旨在增进我们的理解并有助于发现更有效的SYK抑制剂。
