The front cover picture shows a 3D homology model of the human G protein-coupled bile acid receptor (GPBAR1; carbon atoms in green). The full receptor structure is shown (top right) with the proposed binding site of GPBAR1 agonists indicated (red ellipse). The main picture shows a zoom of this binding site into which taurolithocholic acid (TLCA; carbon atoms in cyan) and a 2-phenoxy-nicotinamide agonist (carbon atoms in magenta) are docked. The alignment of TLCA with our advanced lead compounds enabled the identification of the optimal attachment point for a polar vector, which was critical to improve the physicochemical properties of the series. For more details, see the Communication by Rainer E. Martin et al. on p. 569 ff.