Abstract

Lymphocyte-specific protein tyrosine kinase (Lck), a non-receptor Src family kinase, has a vital role in various cellular processes such as cell cycle control, cell adhesion, motility, proliferation, and differentiation. Lck is reported as a key factor regulating the functions of T-cell including the initiation of TCR signalling, T-cell development, in addition to T-cell homeostasis. Alteration in expression and activity of Lck results in numerous disorders such as cancer, asthma, diabetes, rheumatoid arthritis, atherosclerosis, and neuronal diseases. Accordingly, Lck has emerged as a novel target against different diseases. Herein, we amass the research efforts in literature and pharmaceutical patents during the last decade to develop new Lck inhibitors. Additionally, structure-activity relationship studies (SAR) and docking models of these new inhibitors within the active site of Lck were demonstrated offering deep insights into their different binding modes in a step towards the identification of more potent, selective, and safe Lck inhibitors.

摘要

淋巴细胞特异性蛋白酪氨酸激酶 (Lck) 是一种非受体 Src 家族激酶，在细胞周期控制、细胞粘附、运动、增殖和分化等各种细胞过程中起着至关重要的作用。据报道，Lck 是调节 T 细胞功能的关键因素，包括 TCR 信号传导的启动、T 细胞发育以及 T 细胞稳态。Lck 表达和活性的改变导致多种疾病，例如癌症、哮喘、糖尿病、类风湿性关节炎、动脉粥样硬化和神经元疾病。因此，Lck 已成为针对不同疾病的新靶点。在此，我们在过去十年中积累了文献和药物专利的研究成果，以开发新的 Lck 抑制剂。此外，