A Small Molecule Couples PPARα/γ Agonism with Allosteric Enhancement of FXR Activity in Liver cells and MAFLD Model

Supporting materials including: predicted binding mode of RT206 into PPARγ and PPARα (Figure S1), transactivation screening data (Table S1), MM-GBSA binding free-energy estimates (Table S2), HepG2 viability assays (Figure S2), RT-qPCR gene-expression analyses under OCA/RT206 treatments (Figure S3), GCI kinetic binding data for FXR ligands (Figure S4), SiteMap pocket analyses (Figure S5 and Table S3), GG dose–response curves on full-length FXR and FXR chimera in comparison with full agonists CDCA and GW4064 (Figure S7), computational docking/MD evidence for S2-site engagement (Figures S6, S8–S9; Table S4), RMSD stability analyses across apo and ligand-bound FXR systems (Figure S10)