ArticleCell chemical biology2023
Arabinose- and xylose-modified analogs of 2',3'-cGAMP act as STING agonists.
Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- STING agonist profiling by nucleotide library defines structural determinants of cyclic dinucleotide recognition.iScience · 2026Article
- Structural and biochemical insights into the inhibition ofRSC chemical biology · 2026Article
- Extracellular cGAMP in health and disease.Molecular biomedicine · 2026Review
- Activation of stimulator of interferon genes (STING) and inhibition of vascular endothelial growth factor receptor (VEGFR) by telatinib induce antitumor activity.The Journal of biological chemistry · 2026Article
- Precision targeting of STING: Challenges, innovations, and clinical outlook for cancer therapy.Innovation (Cambridge (Mass.)) · 2026Review
- In Silico Prediction of Potential pTLR7/pSTING Dual-Targeting Ligands via Virtual Screening and Molecular Dynamics Simulation.International journal of molecular sciences · 2025Article
- PDE-stable 2'3'-cGAMP analogues, containing 5'-S-phosphorothioester linkage, as STING agonists.RSC medicinal chemistry · 2024Article
- Exploration of the Binding Mechanism of Cyclic Dinucleotide Analogs to Stimulating Factor Proteins and the Implications for Subsequent Analog Drug Design.Biomolecules · 2024Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Stimulator of interferon genes (STING) agonists are promising candidates for vaccine adjuvants and antitumor immune stimulants. The most potent natural agonist of STING, 2',3'-cyclic GMP-AMP (2',3'-cGAMP), is subject to nuclease-mediated inherent metabolic instability, thereby placing limits on its clinical efficacy. Here, we report on a new class of chemically synthesized sugar-modified analogs of 2',3'-cGAMP containing arabinose and xylose sugar derivatives that bind mouse and human STING alleles with high affinity. The co-crystal structures demonstrate that such analogs act as 2',3'-cGAMP mimetics that induce the "closed" conformation of human STING. These analogs show significant resistance to hydrolysis mediated by ENPP1 and increased stability in human serum, while retaining similar potency as 2',3'-cGAMP at inducing IFN-β secretion from human THP1 cells. The arabinose- and xylose-modified 2',3'-cGAMP analogs open a new strategy for overcoming the inherent nuclease-mediated vulnerability of natural ribose cyclic nucleotides, with the additional benefit of high translational potential as cancer therapeutics and vaccine adjuvants.
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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.