Figure 2.

Representation of the pharmacological tools to modulate GPCR heteromers. Currently available pharmacological tools to modulate the generation and/or signaling of receptor heteromers could represent new therapeutic strategies for ASD. (A) Bivalent ligands are composed of two functional pharmacophores, linked by a spacer, that interact with each of the protomers of the heteromers and activate/block its cellular signaling cascade(s). (B) Allosteric modulators bind to distinct binding sites from the endogenous ligands in one of the protomers and can alter its structure (producing a conformational change), dynamics, and function, which will in turn alter the whole heteromer’s functionality. (C) Interference peptides are synthetic peptides harboring the same amino acid sequence as the interacting transmembrane (TM) domains between the two receptors that compose the heteromer: they get inserted into TM domains and disrupt the receptor heteromer by preventing binding between the two receptor protomers.