PPAR gamma inhibitor FX-909

An orally available inverse agonist and inhibitor of the transcription factor (TF) peroxisome proliferator-activated receptor gamma (PPAR gamma; PPARG), with potential antineoplastic activity. Upon oral administration, PPARG inhibitor FX-909 selectively targets and covalently binds to a region of PPARG that is sequestered from the mutation site. The binding promotes a repressive conformation of PPARG and inhibits the activity of PPARG. This inhibits both basal- and ligand-activated transcription by PPARG and prevents PPARG-mediated transcription of target genes, such as FABP4/Fabp4, AGT/Agt, IVT/Ivd and ARG1/Arg1. This may inhibit proliferation in PPARG-overactivated tumor cells. PPARG, a nuclear receptor, is genetically altered, including amplification, missense mutations, and fusions, in certain tumor cells commonly associated with the luminal lineage subtype.