Article

Discovery and characterization of FX-909, a covalent inverse agonist of PPARG rationally designed to impose a powerful repressive bias in PPARG for the treatment of PPARG/RXRA-activated muscle-invasive urothelial cancers

2025-05-10

Abstract excerpt

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. We utilized studies into tumor-associated mutations in both PPARG and RXRA, as well as a combination of structure-based drug design merged with insights from biochemic...

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Literature Corpus work: 0a527a53-9aae-55f0-841a-3b8413deb860
DOI: 10.1101/2025.05.08.652848

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Discovery and characterization of FX-909, a covalent inverse agonist of PPARG rationally designed to impose a powerful repressive bias in PPARG for the treatment of PPARG/RXRA-activated muscle-invasive urothelial cancersDOI 10.1101/2025.05.08.652848Read

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