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Updated: May 21, 2025

Behavioral and Network Pharmacology-Based Analyses for the Traditional Mongolian Medicine Zadi-5 in a Rat Model of Depression
07:58

Behavioral and Network Pharmacology-Based Analyses for the Traditional Mongolian Medicine Zadi-5 in a Rat Model of Depression

Published on: February 24, 2023

438

Development of a TBK1 and ALK dual inhibitor for alleviating depressive behavior via anti-inflammatory effects

Ji Hun Wi1, Hyelim Lee2, Ji Min Park3

  • 1Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|March 21, 2025
PubMed

Polypharmacology offers innovative strategies for treating immune and inflammatory dysregulation in complex diseases. Here, we identified ALS-04, a dual inhibitor of TANK-binding kinase 1 (TBK1) and anaplastic lymphoma kinase (ALK), which are closely linked to stimulator of interferon genes (STING)-mediated immune responses. ALS-04 effectively suppressed 2'3'-cyclic GMP-AMP (cGAMP)- and lipopolysaccharide (LPS)-induced type I interferon and pro-inflammatory responses by targeting the STING-TBK1 and STING-ALK pathways. Furthermore, ALS-04 significantly alleviated depressive symptoms, including anhedonia and behavioral despair, in an LPS-induced mouse model of depression. These findings highlight the therapeutic potential of dual TBK1 and ALK inhibition in depression by modulating immune and inflammatory pathways.

Keywords:
ALKDepressionDual inhibitorInflammationInnate immunityTBK1

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