Fig. 13.

Three extracellular allosteric binding sites in GPCRs and the corresponding small-molecule allosteric modulators. Stick models of small-molecule ligands are mapped to representative members of outside 7TMD (I and II) (GLP-1R, PDB: 6VCB), outside 7TMD (II and III) (GPR101, PDB: 8W8S), and within 7TMD (M4R, PDB: 7V68) GPCRs. The position of an orthosteric ligand of M4R (shown in gray and sphere-and-stick representation) is mapped onto the overview of allosteric modulators for comparison. For each pocket, the number of unique modulators is indicated in boldface type, and the number of GPCRs containing the pocket is indicated in parentheses