Figure 4. GPCR isoforms of drug targets.
a, Number of receptors categorized by the number of tissue expression signatures for all GPCRs (grey) and for those which belong to the 111 targets of 474 FDA-approved drugs (in green). b, Filtering based on structural and expression considerations identifies non-reference isoforms with extracellular structural changes and tissue distribution that is different from the reference isoform, potentially allowing the development of ligands that specifically target them. c, Tissue distribution of the reference and isoform 1 of GPR35. BRET signals were monitored after treatment of HEK-293T cells with varying concentrations of lodoxamide, pamoic acid, and zaprinast using a GPR35-Gα13 SPASM sensor (upper panel; n=3) or eYFP-tagged GPR35 isoforms and β-arrestin 2 tagged with Nanoluciferase (lower panel; n=3, see Methods for further details).