{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE298nnn/GSE298581/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298581"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Global gene expression response to PPARG inhibition in three urothelial cancer cell lines","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":"GSE298581","cross_references":{"GSM":["GSM9017839","GSM9017881","GSM9017880","GSM9017861","GSM9017883","GSM9017882","GSM9017860","GSM9017841","GSM9017885","GSM9017863","GSM9017884","GSM9017862","GSM9017840","GSM9017865","GSM9017843","GSM9017864","GSM9017842","GSM9017886","GSM9017867","GSM9017845","GSM9017844","GSM9017866","GSM9017847","GSM9017869","GSM9017868","GSM9017846","GSM9017849","GSM9017848","GSM9017870","GSM9017850","GSM9017872","GSM9017871","GSM9017874","GSM9017852","GSM9017873","GSM9017851","GSM9017876","GSM9017854","GSM9017875","GSM9017853","GSM9017878","GSM9017856","GSM9017855","GSM9017877","GSM9017858","GSM9017879","GSM9017857","GSM9017859"],"GPL":["34284"],"GSE":["298581"],"taxon":["Homo sapiens"]}}