NR1H4 and metabolic dysfunction-associated steatohepatitis: Although significant progress has been made in manipulating the GW4064 scaffold to enhance druggability, no FXR agonist has yet been approved for NASH treatment.[84, 85, 103, 104, 113, 114, 115] Among the synthesized compounds, 34 and 35 (Figure 3) exhibited potent FXR agonistic activities in vitro (EC50 = 45.2 ± 19.5 nM and 36.1 ± 4.7 nM, respectively) and effectively promoted the expression of target genes in vivo.