TBK1的结构以及小分子抑制剂

Structure of TBK1 and Small Molecule Inhibitors

坦克结合激酶1(Tank-Binding Kinase 1, TBK1)是天然免疫过程的重要调节因子,通过磷酸化干扰素调节因子3(Interferon Regurlartory Factor 3, IRF3)和干扰素调节因子7(Interferon Regurlartory Factor 7, IRF7)可诱导型干扰素和其他促炎细胞因子的产生。TBK1稳态的失调则会导致许多疾病如炎症、自身免疫性疾病、代谢性疾病和癌症的发展。因此,基于TBK1靶点开发新型高效抑制剂可进一步加深我们对于该靶点的认知,并确认其作为药物靶点的有效性。本文就TBK1蛋白结构以及一些有潜力的药物小分子进行综述。

Tank-Binding Kinase 1 (TBK1) is an important regulator of the natural immune process, inducing the production of interferon and other pro-inflammatory cytokines through phosphorylation of interferon regurlartory factor 3 (IRF3) and interferon regurlartory factor 7 (IRF7). Dysregulation of TBK1 homeostasis leads to the development of many diseases such as inflammatory/autoim- mune diseases, metabolic diseases and cancer. Therefore, the development of novel potent inhibitors based on the TBK1 target could further enhance our understanding of this target. Our knowledge of this target and its effectiveness as a drug target can be further enhanced. In this paper, we review the structure of TBK1 protein and some promising drug small molecules.