Hasan Maroof, Yan Nan
Autoimmunity, Transplantation and Inflammation, Novartis Institute of Biomedical Research, CH?4056 Basel, Switzerland.
Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; Departments of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Pharmacol Res. 2016 Sep;111:336-342. doi: 10.1016/j.phrs.2016.04.008. Epub 2016 Jun 25.
The serine/threonine protein kinase, TBK1, plays a crucial role as the hub for many innate immune signaling pathways that lead to the induction of type I interferon (IFN) and interferon-stimulated genes (ISGs). Due to its key function in maintaining homeostasis of the immune system, cell survival and proliferation, TBK1 activity is tightly regulated. Dysregulation of TBK1 activity is often associated with autoimmune diseases and cancer, implicating the potential therapeutic benefit for targeting TBK1. Tremendous effort from both academic institutions and private sectors during the past few years has led to the development of many potent and selective TBK1 inhibitors, many of which have shown great promise in disease models in vivo. This review summarizes recent advance on the pharmacological inhibition of TBK1 and its potential for treating autoimmune diseases and interferonopathies.
丝氨酸/苏氨酸蛋白激酶TBK1作为许多先天性免疫信号通路的枢纽发挥着关键作用,这些信号通路可导致I型干扰素(IFN)和干扰素刺激基因(ISG)的诱导。由于其在维持免疫系统稳态、细胞存活和增殖方面的关键功能,TBK1的活性受到严格调控。TBK1活性失调通常与自身免疫性疾病和癌症相关,这表明靶向TBK1具有潜在的治疗益处。在过去几年中,学术机构和私营部门都付出了巨大努力,开发出了许多强效且选择性的TBK1抑制剂,其中许多在体内疾病模型中已显示出巨大潜力。本综述总结了TBK1药理抑制作用的最新进展及其在治疗自身免疫性疾病和干扰素病方面的潜力。