Researchers from Flare Therapeutics Inc. presented the discovery of a first-in-class covalent peroxisome proliferator-activated receptor γ (PPARγ) inverse agonist, FX-909, being developed for the treatment of urothelial cancer (UC). Synthesis and optimization of covalent lead series of agonists of the PPARγ lineage transcription factor led to the discovery of FX-909 as the lead covalent PPARγ inverse agonist with powerful repressive conformational biasing activity.