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Role of TBK1 Inhibition in Targeted Therapy of Cancer

Xueqing Yang1, Zongliang Liu1

  • 1School 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.

Mini Reviews in Medicinal Chemistry
|February 5, 2024
PubMed

Insights

TANK-binding kinase 1 (TBK1) is vital for immunity and cell processes. TBK1 inhibitors show promise as antitumor agents, aiding tumor immunotherapy research.

Area of Science:

  • Molecular Biology
  • Immunology
  • Oncology

Background:

  • TANK-binding kinase 1 (TBK1) is a serine/threonine kinase regulating immunity, autophagy, cell survival, and proliferation.
  • TBK1 modulates IRF3/7 and NF-κB signaling pathways, impacting cellular activities and contributing to tumor development.
  • TBK1 kinase is a potential therapeutic target for tumor immunotherapy, but its mechanisms require further elucidation.

Purpose of the Study:

  • To review the recent understanding of TBK1's role in tumors.
  • To summarize the development of small molecule inhibitors targeting TBK1.
  • To highlight TBK1 inhibitors as tools for biological investigation and potential cancer therapeutics.

Main Methods:

  • Literature review of TBK1's molecular mechanisms in cancer.
  • Analysis of recent advancements in TBK1 small molecule inhibitor development.
  • Summary of in vitro studies on TBK1 inhibitors' antitumor effects.

Main Results:

  • TBK1 regulates key cellular processes relevant to cancer, including immune response and proliferation.
  • Several TBK1 inhibitors have demonstrated antitumor effects in preclinical in vitro models.
  • Compounds 15, 16, and 21 are examples of TBK1 inhibitors with observed anticancer activity.

Conclusions:

  • TBK1 plays a significant role in tumor biology and immune evasion.
  • Selective TBK1 inhibitors are valuable tools for studying TBK1 function and represent promising candidates for tumor immunotherapy.
  • Further research into TBK1's mechanism and inhibitor development is crucial for advancing cancer treatment.
Keywords:
TBK1cancerimmuneinflammatoryinhibitors.metabolicsignaling pathways

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