ArticleNature chemical biology2014
Hydrolysis of 2'3'-cGAMP by ENPP1 and design of nonhydrolyzable analogs.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 272 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
272 citing papers in PubMed, 500 citations in OpenAlex.
- ENPP3 drives ccRCC progression by cGAMP hydrolysis and STING-IFN suppression.Cancer biology & therapy · 2026Article
- Rational design of next-generation vaccine adjuvants: From molecular mechanisms to hybrid delivery platforms.Human vaccines & immunotherapeutics · 2026Review
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- STING agonist profiling by nucleotide library defines structural determinants of cyclic dinucleotide recognition.iScience · 2026Article
- The DNA damage response and cancer immunotherapy.Nature reviews. Cancer · 2026Review
- STING: An Attractive Target for Autoimmune and Inflammatory Diseases.Medicinal research reviews · 2026Review
- Chemically Regulated STING-Activating Prodrugs of Deoxyribose Cyclic Dinucleotides Elicit Robust Immune Activation and Durable Antitumor Immunity.Angewandte Chemie (International ed. in English) · 2026Article
- The cGAS-STING pathway in inflammaging and neuroinflammation.Science China. Life sciences · 2026Review
- The cGAS/STING pathway in cancer: translating innate DNA sensing into therapeutic potential.The Journal of clinical investigation · 2026Review
- Molecular mechanisms regulating cGAS/STING activation in health and disease.The Journal of clinical investigation · 2026Review
- Viral capsid delivery of cGAMP enhances STING-dependent antitumor immune response.bioRxiv : the preprint server for biology · 2026Article
- Review
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Structural genomics sheds light on protein functions and remote homologs across the insect tree of life.Cell research · 2026Article
- A direct, real-time, spectrophotometric assay for measuring ENPP1-catalyzed cGAMP hydrolysis.The Journal of biological chemistry · 2026Article
- Dual-targeted manganese-doped carbon dots activate the cGAS-STING pathway and immunogenic cell death for potent glioblastoma immunotherapy.Materials today. Bio · 2026Article
- Nano-Enabled Systemic Delivery of STING Agonist by Engineered Silicasome for Potent Antitumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Expanding roles of cGAS-STING signaling in neuroinflammation.The Journal of clinical investigation · 2026Review
- Polyamine sequestration of 2'3'-cGAMP constrains intercellular transmission and STING engagement to subvert antitumor immunity.The Journal of clinical investigation · 2026Article
- Extracellular cGAMP in health and disease.Molecular biomedicine · 2026Review
212 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Agonists of mouse STING (TMEM173) shrink and even cure solid tumors by activating innate immunity; human STING (hSTING) agonists are needed to test this therapeutic hypothesis in humans. The endogenous STING agonist is 2'3'-cGAMP, a second messenger that signals the presence of cytosolic double-stranded DNA. We report activity-guided partial purification and identification of ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP1) to be the dominant 2'3'-cGAMP hydrolyzing activity in cultured cells. The hydrolysis activity of ENPP1 was confirmed using recombinant protein and was depleted in tissue extracts and plasma from Enpp1(-/-) mice. We synthesized a hydrolysis-resistant bisphosphothioate analog of 2'3'-cGAMP (2'3'-cG(s)A(s)MP) that has similar affinity for hSTING in vitro and is ten times more potent at inducing IFN-β secretion from human THP1 monocytes. Studies in mouse Enpp1(-/-) lung fibroblasts indicate that resistance to hydrolysis contributes substantially to its higher potency. 2'3'-cG(s)A(s)MP is therefore improved over natural 2'3'-cGAMP as a model agonist and has potential as a vaccine adjuvant and cancer therapeutic.
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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.