College of Pharmacy, Dongguk University-Seoul, Goyang, Republic of Korea.
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):1574-1602. doi: 10.1080/14756366.2021.1937143.
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.
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、细胞黏附、运动、增殖和分化等多种细胞过程中发挥着重要作用。Lck 被报道为调节 T 细胞功能的关键因素，包括 TCR 信号的启动、T 细胞的发育以及 T 细胞的稳态。Lck 的表达和活性改变会导致许多疾病，如癌症、哮喘、糖尿病、类风湿关节炎、动脉粥样硬化和神经疾病。因此，Lck 已成为针对不同疾病的新型靶标。本文汇集了过去十年中文献和药物专利中的研究成果，以开发新的 Lck 抑制剂。此外，还对这些新抑制剂在 Lck 活性部位的构效关系研究（SAR）和对接模型进行了展示，深入了解了它们在识别更有效、更选择性和更安全的 Lck 抑制剂方面的不同结合模式。
