Fig. 20.

a Five allosteric binding sites in the transmembrane domain outside 7TMD of GPCRs and the corresponding small-molecule allosteric modulators. Stick models of small-molecule ligands are mapped to representative members of outside 7TMD (I–III) (P2Y₁, PDB: 4XNV), outside 7TMD (II–IV) (CB1R, PDB: 6KQI), outside 7TMD (III and V) (C5aR1, PDB: 6C1R), outside 7TMD (V and VI) (CXCR3, PDB: 8HNN), and outside 7TMD (I, VI, and VII) (A1R, PDB: 7LD3) GPCRs. For each pocket, the number of unique modulators is indicated in boldface type, and the number of GPCRs containing the pocket is provided in parentheses. b 2D chemical structures of synthetic small-molecule allosteric ligands targeting the transmembrane domain outside 7TMD of GPCRs. c Extracellular view of the five allosteric sites