GPBAR1 and Pruritus: In 2017, Xiao et al. reported a series of novel bile acids featuring various modifications on the A‐ring and side chain of OCA, with the aim to reduce adverse effects (e.g., pruritus and increased LDL levels) potentially associated with dual activity on GPBAR1.[125] The best lead identified in this study, compound 44 (Figure 4), characterized by a 3,5‐disubstituted isoxazole moiety, bearing a hydroxyl group at the 3‐position, demonstrated high efficacy on FXR (EC50 = 0.03 μM, efficacy = 121%), with a potency six times greater than that of OCA and an EC50 ratio of 17 between FXR and GPBAR1.