{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309742/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309742"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Human STING-specific macrocyclic peptide Nano-P1 displays limited toxicity to MEFs and potently suppresses cGAS-STING activation","description":"Suppression of hyperactive STING may provide therapeutic benefits to treat inflammatory diseases. We identified a macrocyclic peptide, named P1, which binds to human STING (hSTING) by a new platform for the discovery of pseudo-natural macrocyclic peptides. Nano-P1, the nanoparticle form to increase P1 cellular membrane permeability, inhibited the 2'3'-cGAMP induced hSTING activation in Mouse Embryonic Fibroblasts (MEFs). In cellular experiments, Nano-P1 effectively blocked the translocation of hSTING from endoplasmic reticulum (ER) to the trans-Golgi network, increasing the accumulation of hSTING on ER, and thus interrupted the downstream STING signaling transduction, which resulted in reduced production of IFN-β and pro-inflammatory cytokines, the major effectors of STING pathway. Furthermore, in vitro data showed a limited toxicity of Nano-P1 toward MEFs, preliminarily supporting its safety profile in most cell types. Overall, Nano-P1 emerges as a safe and potent hSTING inhibitor for potential application in clinical diseases associated with aberrant cGAS-STING activation.","dates":{"publication":"2026/09/10"},"accession":"GSE309742","cross_references":{"GSM":["GSM9278168","GSM9278167","GSM9278166","GSM9278165","GSM9278164","GSM9278163"],"GPL":["24247"],"GSE":["309742"],"taxon":["Mus musculus"],"PMID":["[41290486]"]}}