TANK-binding kinase 1 (TBK1) (TBK1)

TANK-binding kinase 1 (TBK1) is a multi-functional serine/threonine kinase that serves as a central integrator of innate immune signaling and cellular homeostasis [4, 13]. It is primarily known for its role in the cGAS-STING and TLR pathways, where it phosphorylates interferon regulatory factors (IRF3/7) to induce type I interferon production in response to cytosolic DNA or viral infection [2, 5, 14]. In the context of oncology, TBK1 has emerged as a critical survival factor in KRAS-mutant cancers and a mediator of immune evasion, making it an attractive target for small-molecule inhibitors [4, 8, 15, 17]. Additionally, TBK1 regulates selective autophagy and its dysfunction is genetically linked to neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS) [5, 10, 13]. While several inhibitors like amlexanox and momelotinib have been studied, therapeutic development must balance the need for potent inhibition with the risk of systemic inflammatory side effects and potential hepatotoxicity [4, 11, 15, 16]. The term 'TBK1 phosphorylation cascade' refers to the signaling pathway mediated by this kinase rather than a single molecular target.

Other names

T2KNAKNF-kappa-B-activating kinaseFLJ11330

Inhibition of TBK1 kinase activity, which prevents the phosphorylation of downstream substrates such as IRF3, IRF7, and STING, thereby blocking the production of type I interferons and pro-survival NF-κB signaling [2, 4, 14].