ArticleScience China. Life sciences2024
Targeting STING oligomerization with licochalcone D ameliorates STING-driven inflammatory diseases.
Article in Science China. Life sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- The bidirectional immunoregulatory effects of Traditional Chinese Medicine on the cGAS-STING signaling pathway and their translational prospects.Chinese medicine · 2026Review
- The cGAS-STING pathway in inflammaging and neuroinflammation.Science China. Life sciences · 2026Review
- cGAS-STING signaling in aging and age-related diseases: therapeutic promise and precaution.Archives of pharmacal research · 2026Review
- cGAS/STING Signaling in Ulcerative Colitis: Mechanism and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Machine learning-driven prioritization and experimental validation of traditional Chinese medicine-derived STING-inhibitory candidates.Molecular diversity · 2026Article
- Rational design of carbazole-based STING inhibitors for treating cGAS-STING pathway-driven inflammatory disorders.Nature communications · 2026Article
- Dual Covalent Targeting of STING Cysteines 292/309 Disrupts Functional Oligomerization and Enables Potent Antagonist Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Licochalcone D inhibits osteoclast differentiation and postmenopausal osteoporosis by inactivating the NF-κB signaling pathway.Journal of orthopaedic surgery and research · 2025Article
- Carnosic Acid Directly Targets STING C-Terminal Tail to Improve STING-Mediated Inflammatory Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Licochalcone D mitigates intracerebral hemorrhage-induced ferroptosis of neurons through COX2 inhibition.Frontiers in pharmacology · 2025Article
- cGAS-STING pathway as a promising target for digestive diseases: insights from natural plant products.Frontiers in nutrition · 2025Review
- Progress of cGAS-STING signaling pathway-based modulation of immune response by traditional Chinese medicine in clinical diseases.Frontiers in immunology · 2024Review
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Authors and funding
16 authors.
Funding
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Abstract
The development of STING inhibitors for the treatment of STING-related inflammatory diseases continues to encounter significant challenges. The activation of STING is a multi-step process that includes binding with cGAMP, self-oligomerization, and translocation from the endoplasmic reticulum to the Golgi apparatus, ultimately inducing the expression of IRF3 and NF-κB-mediated interferons and inflammatory cytokines. It has been demonstrated that disruption of any of these steps can effectively inhibit STING activation. Traditional structure-based drug screening methodologies generally focus on specific binding sites. In this study, a TransformerCPI model based on protein primary sequences and independent of binding sites is employed to identify compounds capable of binding to the STING protein. The natural product Licochalcone D (LicoD) is identified as a potent and selective STING inhibitor. LicoD does not bind to the classical ligand-binding pocket; instead, it covalently modifies the Cys148 residue of STING. This modification inhibits STING oligomerization, consequently suppressing the recruitment of TBK1 and the nuclear translocation of IRF3 and NF-κB. LicoD treatment ameliorates the inflammatory phenotype in Trex1
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