ArticleNature communications2023
Development of cyclopeptide inhibitors of cGAS targeting protein-DNA interaction and phase separation.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 42 citations in OpenAlex.
- Dataset of RNA-seq profiles from THP-1-derived macrophages pretreated with AZD7648 and stimulated with CT DNA.Data in brief · 2026Article
- [Mechanisms of cGAS-STING-mediated chronic inflammation and targeted interventions in brain aging].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- Reprogramming innate immunity through viral interference: A double-edged strategy for enhancing and containing gene therapies.Molecular therapy. Nucleic acids · 2026Review
- A designed peptide disrupting viral protease cleavage restores cGAS-DNA phase separation and type I interferon responses.PLoS pathogens · 2026Article
- Roles of the cGAS-STING signaling pathway in viral latency.Journal of virology · 2026Review
- Peptide Coacervates Promote Cytosolic Delivery of STING Agonists for Cancer Immunotherapy.Vaccines · 2026Article
- Graph-based deep learning approach for high-throughput protein-DNA interaction scoring.Acta pharmacologica Sinica · 2026Article
- Machine Learning-Guided Engineering of Protein Phase Separation Properties in Immune Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Prasugrel inhibits TLR7-driven autoimmunity in systemic lupus erythematosus by acetylating cGAS.Nature communications · 2026Article
- Article
- PRRs-Dependent and Independent Mechanisms of STING Signaling in Inflammatory and Autoimmune Diseases.Biomedicines · 2025Review
- Membraneless Organelles and Phase Separation in Tumours: Mechanisms and Prospects.Cell proliferation · 2025Review
- De novo design of protein condensation inhibitors by targeting an allosteric site of cGAS.Nature communications · 2025Article
- cGAS, an innate dsDNA sensor with multifaceted functions.Cell insight · 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
- The CGAS-STING1 Pathway as a Mediator of Innate Immune Response in Cardiovascular Disease.JACC. Asia · 2025Review
- The cGAS-STING pathway in cancer immunity: dual roles, therapeutic strategies, and clinical challenges.Essays in biochemistry · 2025Review
- The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer's disease.Molecular neurodegeneration · 2025Review
- Microglial cGAS Deletion Preserves Intercellular Communication and Alleviates Amyloid-β-Induced Pathogenesis of Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Innate Immune Sensor Zbp1 Mediates Central Nervous System Inflammation Induced by Angiostrongylus Cantonensis by Promoting Macrophage Inflammatory Phenotypes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclic GMP-AMP synthase (cGAS) is an essential sensor of aberrant cytosolic DNA for initiating innate immunity upon invading pathogens and cellular stress, which is considered as a potential drug target for autoimmune and autoinflammatory diseases. Here, we report the discovery of a class of cyclopeptide inhibitors of cGAS identified by an in vitro screening assay from a focused library of cyclic peptides. These cyclopeptides specifically bind to the DNA binding site of cGAS and block the binding of dsDNA with cGAS, subsequently inhibit dsDNA-induced liquid phase condensation and activation of cGAS. The specificity and potency of one optimal lead XQ2B were characterized in cellular assays. Concordantly, XQ2B inhibited herpes simplex virus-1 (HSV-1)-induced antiviral immune responses and enhanced HSV-1 infection in vitro and in vivo. Furthermore, XQ2B significantly suppressed the elevated levels of type I interferon and proinflammatory cytokines in primary macrophages from Trex1
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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.