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Allosteric ligands for CB1 are capable of modulating orthosteric ligand (agonist) activity. A, Schematic representation of the CB1 receptor TMD bundle illustrating the topographic distinction between allosteric and orthosteric binding sites. B, Structures of representative allosteric modulators for CB1 including ORG27569, PSNCBAM-1, lipoxin A4, RTI371, and LDK1256 and LDK1258 (also referred to as compounds 12d and 12f from Ref. 46).
