ArticleNature communications2024
Small molecule induced STING degradation facilitated by the HECT ligase HERC4.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- STING: An Attractive Target for Autoimmune and Inflammatory Diseases.Medicinal research reviews · 2026Review
- A molecular glue induces aberrant STING oligomerization and inhibits autoinflammatory diseases.Signal transduction and targeted therapy · 2026Article
- Article
- Evaluation of Novel Cloxyquin Analogs for KArchiv der Pharmazie · 2026Article
- Therapeutic targeting of the cGAS-STING pathway in human disease.The Journal of clinical investigation · 2026Review
- Interstitial lung disease and the STING pathway.The Journal of clinical investigation · 2026Review
- HECT ubiquitin ligases as regulators of inflammatory signalling.Cell death and differentiation · 2026Review
- IFIT3 stabilizes STING via USP18 to drive M1 macrophage polarization and early inflammation in acute lung injury.Cellular and molecular life sciences : CMLS · 2026Article
- A Novel Paradigm for Targeting Challenging Targets: Advancing Technologies and Future Directions of Molecular Glue Degraders.Molecules (Basel, Switzerland) · 2026Review
- Stenotrophomonas promotes gastrointestinal tumor progression via STING degradation in tumour cells and mitigated immune response.Nature communications · 2026Article
- Role of dual specificity phosphatase 1 in influencing inflammatory pathways in macrophages modulated byFrontiers in immunology · 2026Article
- eVGeMdb: a manually curated database for experimentally validated genetic modifiers of neurodegenerative disorders.NAR molecular medicine · 2026Article
- Nucleic Acid Diversity in cGAS-STING Pathway Activation and Immune Dysregulation.Biomedicines · 2025Review
- Role of Dual Specificity Phosphatase 1 (DUSP1) in influencing inflammatory pathways in macrophages modulated bybioRxiv : the preprint server for biology · 2025Article
- STING-targeting PROTACs: emerging therapeutic tools for enhanced immunotherapy in inflammatory diseases.Frontiers in immunology · 2025Review
- Autoinflammatory patients with Golgi-trapped CDC42 exhibit intracellular trafficking defects leading to STING hyperactivation and ER stress.Nature communications · 2024Article
- cGAS/STING signalling pathway in senescence and oncogenesis.Seminars in cancer biology · 2024Review
- Targeted Protein Degradation: Current and Emerging Approaches for E3 Ligase Deconvolution.Journal of medicinal chemistry · 2024Review
Corrections and comments
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Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stimulator of interferon genes (STING) is a central component of the cytosolic nucleic acids sensing pathway and as such master regulator of the type I interferon response. Due to its critical role in physiology and its' involvement in a variety of diseases, STING has been a focus for drug discovery. Targeted protein degradation (TPD) has emerged as a promising pharmacology for targeting previously considered undruggable proteins by hijacking the cellular ubiquitin proteasome system (UPS) with small molecules. Here, we identify AK59 as a STING degrader leveraging HERC4, a HECT-domain E3 ligase. Additionally, our data reveals that AK59 is effective on the common pathological STING mutations, suggesting a potential clinical application of this mechanism. Thus, these findings introduce HERC4 to the fields of TPD and of compound-induced degradation of STING, suggesting potential therapeutic applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.