Given that A3AR is a GPCR with seven-transmembrane helices24 and TMIGD3 i1 preserves a part of the A3AR structure, we questioned whether TMIGD3 i1 could regulate signalling similar to A3AR, which is known to inhibit three major cancer-associated signalling including the NF-κB, β-catenin and Erk pathways (Supplementary Fig. 5a)25, 26. Here, ADORA3 is linked to cancer.