ArticleCellular and molecular life sciences : CMLS2023
Development of VHL-recruiting STING PROTACs that suppress innate immunity.
Article in Cellular and molecular life sciences : CMLS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- STING: An Attractive Target for Autoimmune and Inflammatory Diseases.Medicinal research reviews · 2026Review
- Adult-onset STING-associated vasculopathy.Journal of human immunity · 2026Article
- Therapeutic targeting of the cGAS-STING pathway in human disease.The Journal of clinical investigation · 2026Review
- Therapeutic targeting of neuroimmune mechanisms in neurodegeneration.Nature reviews. Drug discovery · 2026Review
- RSK4 promotes the metastasis of clear cell renal cell carcinoma by activating RUNX1-mediated angiogenesis.Cancer biology & therapy · 2025Article
- PRRs-Dependent and Independent Mechanisms of STING Signaling in Inflammatory and Autoimmune Diseases.Biomedicines · 2025Review
- Macromolecular Diamidobenzimidazole Conjugates Can Activate Stimulator of Interferon Genes.Journal of the American Chemical Society · 2025Article
- Targeting the cGAS-STING Pathway to Modulate Immune Inflammation in Diabetes and Cardiovascular Complications: Mechanisms and Therapeutic Insights.Current issues in molecular biology · 2025Review
- Conjugated STING agonists.Molecular therapy. Nucleic acids · 2025Review
- Design, synthesis, and evaluation of thiazolecarboxamide derivatives as stimulator of interferon gene inhibitors.Molecular diversity · 2025Article
- STING-targeting PROTACs: emerging therapeutic tools for enhanced immunotherapy in inflammatory diseases.Frontiers in immunology · 2025Review
- Gene Expression Dysregulation in Whole Blood of Patients withInternational journal of molecular sciences · 2024Article
- cGAS/STING signalling pathway in senescence and oncogenesis.Seminars in cancer biology · 2024Review
- The balance of STING signaling orchestrates immunity in cancer.Nature immunology · 2024Review
- Review
- At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
STING acts as a cytosolic nucleotide sensor to trigger host defense upon viral or bacterial infection. While STING hyperactivation can exert anti-tumor effects by increasing T cell filtrates, in other contexts hyperactivation of STING can contribute to autoimmune and neuroinflammatory diseases. Several STING targeting agonists and a smaller subset of antagonists have been developed, yet STING targeted degraders, or PROTACs, remain largely underexplored. Here, we report a series of STING-agonist derived PROTACs that promote STING degradation in renal cell carcinoma (RCC) cells. We show that our STING PROTACs activate STING and target activated/phospho-STING for degradation. Locking STING on the endoplasmic reticulum via site-directed mutagenesis disables STING translocation to the proteasome and resultingly blocks STING degradation. We also demonstrate that PROTAC treatment blocks downstream innate immune signaling events and attenuates the anti-viral response. Interestingly, we find that VHL acts as a bona fide E3 ligase for STING in RCC; thus, VHL-recruiting STING PROTACs further promote VHL-dependent STING degradation. Our study reveals the design and biological assessment of VHL-recruiting agonist-derived STING PROTACs, as well as demonstrates an example of hijacking a physiological E3 ligase to enhance target protein degradation via distinct mechanisms.
Indexed as
Identifiers
What OpenQuestion holds
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.