ArticlePloS one2017
Discovery of PF-06928215 as a high affinity inhibitor of cGAS enabled by a novel fluorescence polarization assay.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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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.
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Who cites it
102 citing papers in PubMed, 159 citations in OpenAlex.
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- cGAS-STING axis: A central regulator of neural homeostasis and neuroinflammatory pathogenesis.Neural regeneration research · 2026Article
- A sinomenine derivative protects life-threatening inflammatory injuries via covalently binding to a novel allosteric inhibition site of IRF3.Acta pharmacologica Sinica · 2026Article
- Targeting Nipah virus replication: A fluorescence polarization assay for high-throughput modulators screening against the NThe Journal of biological chemistry · 2026Article
- ELISA-Based Enzyme Kinetics Assay for Measuring cGAS Activity.Bio-protocol · 2026Article
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- The cGAS-STING pathway at the crossroads of neuroimmunology: bridging innate immunity to aging and neurodegeneration.Biomarker research · 2026Review
- The cGAS-STING pathway in fibroblast microenvironment: from molecular mechanisms to targeted therapies.Apoptosis : an international journal on programmed cell death · 2026Review
- Lipid nanoparticle-formulated DNA acts as a potent immune modulator for cancer immunotherapy through interferon signaling pathways.Theranostics · 2026Article
- The cGAS-STING pathway in tumor immunity: dual roles, regulatory mechanisms, and precision therapeutic strategies.Frontiers in pharmacology · 2026Review
- Research progress on the mechanisms of cGAS-STING signaling in immune cell infiltration associated with vascular remodeling.Journal of translational medicine · 2025Review
- The cGAS-STING Pathway in Pulmonary Diseases: Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Synthesis and biological evaluation of pyrano and furano fused ring isoflavene derivatives.RSC advances · 2025Article
- PRRs-Dependent and Independent Mechanisms of STING Signaling in Inflammatory and Autoimmune Diseases.Biomedicines · 2025Review
- Targeting the cGAS-STING Pathway to Modulate Immune Inflammation in Diabetes and Cardiovascular Complications: Mechanisms and Therapeutic Insights.Current issues in molecular biology · 2025Review
- Damage-associated molecular patterns (DAMPs) in diseases: implications for therapy.Molecular biomedicine · 2025Review
- Emerging role of the cGAS-STING pathway in cardiovascular diseases: biologic function, mechanisms and targeted therapy.Molecular medicine (Cambridge, Mass.) · 2025Review
- De novo design of protein condensation inhibitors by targeting an allosteric site of cGAS.Nature communications · 2025Article
- cGAS-STING: mechanisms and therapeutic opportunities.Science China. Life sciences · 2025Review
- Identification and development of cGAS inhibitors and their uses to treat Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
41 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclic GMP-AMP synthase (cGAS) initiates the innate immune system in response to cytosolic dsDNA. After binding and activation from dsDNA, cGAS uses ATP and GTP to synthesize 2', 3' -cGAMP (cGAMP), a cyclic dinucleotide second messenger with mixed 2'-5' and 3'-5' phosphodiester bonds. Inappropriate stimulation of cGAS has been implicated in autoimmune disease such as systemic lupus erythematosus, thus inhibition of cGAS may be of therapeutic benefit in some diseases; however, the size and polarity of the cGAS active site makes it a challenging target for the development of conventional substrate-competitive inhibitors. We report here the development of a high affinity (KD = 200 nM) inhibitor from a low affinity fragment hit with supporting biochemical and structural data showing these molecules bind to the cGAS active site. We also report a new high throughput cGAS fluorescence polarization (FP)-based assay to enable the rapid identification and optimization of cGAS inhibitors. This FP assay uses Cy5-labelled cGAMP in combination with a novel high affinity monoclonal antibody that specifically recognizes cGAMP with no cross reactivity to cAMP, cGMP, ATP, or GTP. Given its role in the innate immune response, cGAS is a promising therapeutic target for autoinflammatory disease. Our results demonstrate its druggability, provide a high affinity tool compound, and establish a high throughput assay for the identification of next generation cGAS inhibitors.
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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.