{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE298nnn/GSE298628/"]},"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=GSE298628"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Genome-wide occupancy of PPARG and RXRA after treatment with PPARG inverse agonist","description":"We report our mechanistic investigation into the conformationally-driven activation bias of PPARG in muscle-invasive urothelial cancer (MIUC) and our efforts to pharmacologically reverse this activation bias through covalent PPARG inverse agonism. Studies into tumor-associated mutations in both PPARG and RXRA were integrated with structure-based drug design as well as insights from biochemical mechanistic studies to discover FX-909, a first-in-class clinical PPARG inverse agonist that robustly enforces a conformationally repressive state of PPARG, even in highly activated biological contexts. FX-909 is a potent, highly selective, and powerful suppressor of PPARG transcriptional activity through enhancement of PPARG-NCOR (Nuclear Co-Repressor) binding affinity. Treatment with FX-909 resulted in selective growth inhibition in PPARG-activated MIUC cell lines. Further, FX-909 achieved durable regressions in xenograft models of MIUC. FX-909 is the first chemical tool that is capable of recapitulating PPARG genetic knockout in vivo and is currently in clinical development for the treatment of intractable MIUC.","dates":{"publication":"2026/05/28"},"accession":"GSE298628","cross_references":{"GSM":["GSM9019641","GSM9019640","GSM9019643","GSM9019642","GSM9019645","GSM9019644","GSM9019647","GSM9019646","GSM9019649","GSM9019648"],"GPL":["20795"],"GSE":["298628"],"taxon":["Homo sapiens"]}}