{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE290nnn/GSE290711/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290711"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Pharmacological Activation of Metal Responsive Transcription Factor 1 by Liganding of Nucleophosmin","description":"Metal responsive transcription factor-1 (MTF-1) enacts a pro-protective, homeostatic transcriptional program in response to heavy metal stress. Activation of MTF-1 in model organisms protects against heavy metal toxicity, forestalls neurodegeneration, and extends life, suggesting that pharmacological agents which augment MTF-1 driven transcription may have the potential to ameliorate pathology associated with heavy metals. Here, we report the discovery of sARM518, a small molecule which robustly activates MTF-1 transcriptional activity in human cells and protects against heavy metal and oxidative stress. Chemical proteomics revealed the cellular target of sARM518 to be nucleophosmin (NPM1), a protein that directly associates with zinc-bound MTF-1 in response to sARM518 treatment, promoting a nuclear, transcriptionally active form of MTF-1. This work affords the first pharmacological activator of MTF-1 and establishes NPM1 as a central, druggable regulator of a cellular stress response.","dates":{"publication":"2026/09/30"},"accession":"GSE290711","cross_references":{"GSM":["GSM8819964","GSM8819962","GSM8819963"],"GPL":["30173"],"GSE":["290711"],"taxon":["Homo sapiens"]}}