FTX-6746

Material and The PPARG inhibitor FTX-6746 was evaluated in UC cell lines including UMUC9 (PPARG amplification) and HT1197 (RXRA-S427F hotspot mutation), which activate PPARG by different genetic mechanisms... These collective results suggest that PPARG is a lineage-defining transcription factor in UC and small molecule PPARG inhibition will be an effective therapy for patients with advanced urothelial cancer harboring the luminal subtype. Model Dose (mg/kg) Schedule %Tumor Growth Inhibition %Target Gene Suppression (D2) UMUC9 3 BID*20 59 16 UMUC9 10 BID*20 70 ND UMUC9 30 BID*20 83 73 UMUC9 30 BID*21 105 80 UMUC9 60 BID*21 108 ND HT1197 30 BID*42 85 46 HT1197 60 BID*42 112 59