Tropifexor, LJN452, is a nonbile acid FXR agonist with subnanomolar activity due to a special bicyclic nortropine-substituted benzothiazole carboxylic acid moiety that has been optimized for improved fit into the ligand-binding domain of FXR.79 In rodent models of non-alcoholic steatohepatitis (NASH)79,80 and cholestasis,81 tropifexor shown greater effectiveness than OCA and effectively regulated FXR-target genes in the intestine and liver. Here, NR1H4 is linked to metabolic dysfunction-associated steatohepatitis.