ArticleCell reports2014
Binding-pocket and lid-region substitutions render human STING sensitive to the species-specific drug DMXAA.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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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
55 citing papers in PubMed, 99 citations in OpenAlex.
- The cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances.Apoptosis : an international journal on programmed cell death · 2026Review
- Purine and pyrimidine-based bacterial cyclic dinucleotides egress the phagosome and activate the innate immune sensor STING.Immunity · 2026Article
- Discovery of MK-2118, a Small-Molecule Agonist of STING.ACS medicinal chemistry letters · 2026Article
- Characterization of a transmembrane-activating STING agonist using genetically humanized mice.Cell reports · 2026Article
- Boosting the immune response and protective efficacy of inactivated PRV vaccine using cGAMP as a mucosal adjuvant.BMC veterinary research · 2026Article
- 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
- Chlorogenic acid promotes mtDNA leakage to enhance cGAS-STING induced anti-tumor immunity via ATF5-mtHSP70-TFAM system.International journal of biological sciences · 2026Article
- Progress Update on STING Agonists as Vaccine Adjuvants.Vaccines · 2025Review
- Targeting cGAS-STING: modulating the immune landscape of hepatic diseases.Frontiers in immunology · 2025Review
- A Purely Biomanufactured System for Delivering Nanoparticles and STING Agonists.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Nanomedicines harnessing cGAS-STING pathway: sparking immune revitalization to transform 'cold' tumors into 'hot' tumors.Molecular cancer · 2024Review
- Design, synthesis, and STING-agonistic activity of benzo[b]thiophene-2-carboxamide derivatives.Molecular diversity · 2024Article
- Agonists and Inhibitors of the cGAS-STING Pathway.Molecules (Basel, Switzerland) · 2024Review
- Structural Evaluations of a Selective Human STINGACS medicinal chemistry letters · 2024Article
- Differential Regulation of the STING Pathway in Human Papillomavirus-Positive and -Negative Head and Neck Cancers.Cancer research communications · 2024Article
- 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a partial STING agonist, competes for human STING activation.Frontiers in immunology · 2024Article
- The Many Ways to Deal with STING.International journal of molecular sciences · 2023Review
- Unlocking STING as a Therapeutic Antiviral Strategy.International journal of molecular sciences · 2023Review
- Discovery of Novel STING Inhibitors Based on the Structure of the Mouse STING Agonist DMXAA.Molecules (Basel, Switzerland) · 2023Article
- cGAMP-activated cGAS-STING signaling: its bacterial origins and evolutionary adaptation by metazoans.Nature structural & molecular biology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The drug DMXAA (5,6-dimethylxanthenone-4-acetic acid) showed therapeutic promise against solid tumors in mouse models but subsequently failed in human clinical trials. DMXAA was later discovered to activate mouse, but not human, STING, an adaptor protein in the cyclic dinucleotide cGAMP-mediated signaling pathway, inducing type I interferon expression. To facilitate the development of compounds that target human STING, we combined structural, biophysical, and cellular assays to study mouse and human chimeric proteins and their interaction with DMXAA. We identified a single substitution (G230I) that enables a DMXAA-induced conformational transition of hSTING from an inactive "open" to an active "closed" state. We also identified a substitution within the binding pocket (Q266I) that cooperates with G230I and the previously identified S162A binding-pocket point substitution, rendering hSTING highly sensitive to DMXAA. These findings should facilitate the reciprocal engineering of DMXAA analogs that bind and stimulate wild-type hSTING and their exploitation for vaccine-adjuvant and anticancer drug development.
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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.