GRK5/6 Inhibitor (Cmpd 18)

Figure 1. Inhibition of GRK-mediated β2 adrenergic receptor (β2) phosphorylation by GRK5/6 Inhibitor (Cmpd 18). HEK293 ΔGRK3/5/6 (GRK2) or ΔGRK2/5/6 (GRK3) or ΔGRK2/3/6 (GRK5) or ΔGRK2/3/5 (GRK6) stably expressing the β2 were preincubated with increasing concentrations of the  GRK5/6 Inhibitor (Cmpd 18) (30 min, 37°C) prior to treatment with 10 µM isoproterenol (ISO) (30 min, 37°C). Receptor phosphorylation was assessed using the 7TM phosphorylation assay and data were normalized to 10 µM ISO without inhibitor.

Figure 2. Comparison of GRK5 inhibition of GRK-mediated β2 adrenergic receptor (β2) phosphorylation by GRK5/6 Inhibitor (Cmpd 18) or GRK5/6 Inhibitor 2 (Cmpd 19). HEK293 ΔGRK2/3/6 stably expressing the β2 were preincubated with increasing concentrations of the GRK5/6 Inhibitor (Cmpd 18) or GRK5/6 Inhibitor 2 (Cmpd 19) (30 min, 37°C) prior to treatment with 10 µM isoproterenol (ISO) (30 min, 37°C). Receptor phosphorylation was assessed using the 7TM phosphorylation assay and data were normalized to 10 µM ISO without inhibitor.

Figure 3. Comparison of GRK6 inhibition of GRK-mediated β2 adrenergic receptor (β2) phosphorylation by GRK2/3 Inhibitor (Cmpd 8h) or GRK5/6 Inhibitor 2 (Cmpd 19). HEK293 ΔGRK2/3/5 stably expressing the β2 were preincubated with increasing concentrations of the GRK5/6 Inhibitor (Cmpd 18) or GRK5/6 Inhibitor 2 (Cmpd 19) (30 min, 37°C) prior to treatment with 10 µM isoproterenol (ISO) (30 min, 37°C). Receptor phosphorylation was assessed using the 7TM phosphorylation assay and data were normalized to 10 µM ISO without inhibitor.

Figure 4. Chemical Structure of GRK5/6 Inhibitor (Cmpd 18). 

Cell-based and isoform-selective G protein-coupled receptor kinase assays for 
comprehensive inhibitor evaluation

 Nina K Blum, Manuela C Kiefer, Angelika Decker, Laura Klement, Edda S F Matthees, Verena Weitzel, Falko Nagel, Babu Joseph, Julia Drube, David Uehling, Carsten Hoffmann, Stefan Schulz Commun Biol 2026 Jan 16. doi: 10.1038/s42003-026-09568-0. PMID: 41545717