Title:Role of TBK1 Inhibition in Targeted Therapy of Cancer
Volume: 24
Issue: 10
Author(s): Xueqing Yang and Zongliang Liu*
Affiliation:
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry
of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of
Shandong, Yantai University, Yantai, China
Keywords:
TBK1, signaling pathways, cancer, immune, metabolic, inflammatory, inhibitors.
Abstract: TANK-binding kinase 1 (TBK1) is a serine/threonine protein that plays a crucial role in
various biological processes like immunity, autophagy, cell survival, and proliferation. The level
and kinase activity of the TBK1 protein is regulated through post-translational modifications
(PTMs). TBK1 mainly mediates the activation of IRF3/7 and NF-κB signaling pathways while also
participating in the regulation of cellular activities such as autophagy, mitochondrial metabolism,
and cell proliferation. TBK1 regulates immune, metabolic, inflammatory, and tumor occurrence and
development within the body through these cellular activities. TBK1 kinase has emerged as a promising
therapeutic target for tumor immunity. However, its molecular mechanism of action remains
largely unknown. The identification of selective TBK1 small molecule inhibitors can serve as valuable
tools for investigating the biological function of TBK1 protein and also as potential drug candidates
for tumor immunotherapy. The current research progress indicates that some TBK1 inhibitors
(compounds 15,16 and 21) exhibit certain antitumor effects in vitro culture systems. Here, we summarize
the mechanism of action of TBK1 in tumors in recent years and the progress of small molecule
inhibitors of TBK1.
