Therapeutic potential for inhibiting TBK1 in autoimmune diseases and interferonopathies

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 immune system, cell survival and proliferation, TBK1 activity is tightly regulated. Dysregulation of TBK1 activity is 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 will summarize these effort in recent years on the pharmacological inhibition of TBK1 in various autoimmune diseases and interferonopathies