GSK180736A

Description: GSK180736A was developed as a novel and potent Rho-associated, coiled-coil-containing protein kinase (ROCK) inhibitor which binds to GRK2 (G protein-coupled receptor kinase 2) with IC50 of 0.77 uM; G protein-coupled receptors (GPCRs) are central to many physiological processes. Regulation of this superfamily of receptors is controlled by GPCR kinases (GRKs), some of which have been implicated in heart failure. GSK180736A shows >=400-fold selectivity for GRK2 over both GRK1 and GRK5. GSK180736A is structurally similar to paroxetine. 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 uM, but highly potent against ROCK1 with IC50 of 100 nM.

References: ACS Chem Biol. 2015 ; 10:310-9; J Biol Chem. 2015; 290:20649-59; J Med Chem. 2016; 59(8):3793-807.