GSK180736A

GSK180736A is a G protein-coupled receptor kinase 2 (GRK2) inhibitor with an IC50 of 0.77 μM.

Signaling Pathways >> Cell Cycle/DNA Damage >> ROCK

Signaling Pathways >> Stem Cell/Wnt >> ROCK

Signaling Pathways >> TGF-beta/Smad >> ROCK

Research Areas >> Cardiovascular Disease

ROCK1:100 nM (IC50)

GRK2:770 nM (IC50)

GSK180736A is a compound structurally similar to paroxetine that is developed as a ROCK inhibitor, is shown to be an even more potent and selective inhibitor of GRK2 with an IC50 of 0.77 μM and more than 100-fold selectivity over other GRKs. ROCK1 is a potential therapeutic target in the treatment of cardiovascular diseases such as hypertension. GSK180736A is a weak inhibitor of PKA with an IC50 of 30 μM, but highly potent against ROCK1 (IC50=100 nM)[1].

Cardiac myocytes are isolated from LV free wall and septum of C57/Bl6 mice. Cells are treated with isoproterenol (0.5 μM) for 2 min for the recording of contraction, with pretreatment of either PBS as vehicle or paroxetine (10 μM), 215022 (0.1, 0.5, 1, 10 μM), 215023 (0.1, 0.5, 1, 10 μM), 224064 (0.1, 0.5, 1, 10 μM), and GSK180736A ( 0.5, 1 μM), for 10 min[1].

[1]. Waldschmidt HV, et al. Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors. J Med Chem. 2016 Apr 28;59(8):3793-807.

Y-27632 2HCl | Fasudil Hydrochloride | KD025(SLx-2119) | Narciclasine | Y-39983 HCl | Thiazovivin | GSK429286A | GSK 269962 | SR-3677 | TC-S 7001 | K-115 | RKI-1447 | LX7101 | Chroman 1 | H-1152 (dihydrochloride)