Chemical biology-based approaches to study adenosine A_2A − dopamine D₂ receptor heteromers

Increasingly, evidence shows G protein-coupled receptors (GPCRs) exist not only as receptor monomers, but also homo- and heteromeric complexes. The interplay between different co-expressed GPCRs contributes to complex signalling profiles when targeting individual receptors [1]. The discovery of adenosine A2A receptor subtype (A2AR) heteromeric complexes with the dopamine D2 receptor (D2R) [2,3,4] has led to the development of A2AR-D2R heterobivalent ligands to simultaneously target both receptors in the complex [5, 6]. Heterobivalent ligands targeting A2AR-D2R complexes provides new opportunities to enhance our understanding of GPCR function using various molecular pharmacology and structural biology approaches [7, 8] and support drug discovery efforts for potential novel treatments for Parkinson’s disease [9, 10] and schizophrenia [11].