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Review
. 2021 Mar;17(1):85-108.
doi: 10.1007/s11302-020-09753-8. Epub 2020 Dec 12.

Molecular probes for the human adenosine receptors

Xue Yang  1 , Laura H Heitman  1 , Adriaan P IJzerman  1 , Daan van der Es  2
Affiliations
Review

Molecular probes for the human adenosine receptors

Xue Yang et al. Purinergic Signal. 2021 Mar.

Abstract

Adenosine receptors, G protein-coupled receptors (GPCRs) that are activated by the endogenous ligand adenosine, have been considered potential therapeutic targets in several disorders. To date however, only very few adenosine receptor modulators have made it to the market. Increased understanding of these receptors is required to improve the success rate of adenosine receptor drug discovery. To improve our understanding of receptor structure and function, over the past decades, a diverse array of molecular probes has been developed and applied. These probes, including radioactive or fluorescent moieties, have proven invaluable in GPCR research in general. Specifically for adenosine receptors, the development and application of covalent or reversible probes, whether radiolabeled or fluorescent, have been instrumental in the discovery of new chemical entities, the characterization and interrogation of adenosine receptor subtypes, and the study of adenosine receptor behavior in physiological and pathophysiological conditions. This review summarizes these applications, and also serves as an invitation to walk another mile to further improve probe characteristics and develop additional tags that allow the investigation of adenosine receptors and other GPCRs in even finer detail.

Keywords: Adenosine receptors; Chemical biology; Covalent ligands; Fluorescent ligands; GPCR; PET ligands; Probes; Radioligands.

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Conflict of interest statement

X Yang declares that she has no conflict of interest.

L.H. Heitman declares that she has no conflict of interest.

A.P. IJzerman declares that he has no conflict of interest.

D van der Es declares that he has no conflict of interest.

Figures

Fig. 1
Fig. 1
Chemical structures of commonly used AR radioligands for in vitro studies. Unlabeled version was drawn for radioligands with unknown radioisotope position (i.e., [3H]LUF5834 and [3H]BAY 60-6583)
Fig. 2
Fig. 2
Chemical structures of AR radioligand tracers for in vivo studies
Fig. 3
Fig. 3
Chemical structures of recent fluorescent tools for ARs
Fig. 4
Fig. 4
Chemical structures of covalent ligands for A1R. LUF7747 is a reversible control ligand for LUF7746
Fig. 5
Fig. 5
Chemical structures of covalent ligands for A2AR
Fig. 6
Fig. 6
Chemical structures of covalent ligands for A3R. LUF7714 is a reversible control ligand for LUF7602
See this image and copyright information in PMC

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