1359959-42-4Relevant articles and documents
Highly potent and selective fluorescent antagonists of the human adenosine A3 receptor based on the 1,2,4-triazolo[4,3-a]quinoxalin-1-one scaffold
Vernall, Andrea J.,Stoddart, Leigh A.,Briddon, Stephen J.,Hill, Stephen J.,Kellam, Barrie
, p. 1771 - 1782 (2012/05/04)
The adenosine-A3 receptor (A3AR) is a G protein-coupled receptor that shows promise as a therapeutic target for cancer, glaucoma, and various autoimmune inflammatory disorders, and as such, there is a need for molecular probes to study this receptor. Here, we report a series of fluorescent ligands containing different linkers and fluorophores based around a 1,2,4-triazolo[4,3-a]quinoxalin-1-one antagonist. One of these conjugates (19) displayed high affinity for the A3AR (pKD = 9.36 ± 0.12) and is >650-fold selective over other adenosine receptor subtypes. Confocal microscopy revealed clear, displaceable membrane labeling of CHO-A 3 cells with 19, with no detectable labeling of CHO-A1 cells under identical conditions. This fluorescent ligand was also able to specifically label the A3AR in HEK293T cells containing a mixed adenosine receptor population. The subtype specificity, along with its excellent imaging properties, make 19 an ideal tool for studying A3AR distribution and organization, particularly in the presence of other adenosine receptor subtypes.
