GSK429286A

GSK429286A is a selective inhibitor of ROCK1 with an IC₅₀ value of 14 nM. IC50 & Target:IC50: 14 nM (ROCK1)^[1]. In Vitro:GSK429286A at 1 μM reduces ROCK2 activity over 20-fold, under conditions in which the only other kinase tested that is significantly inhibited is MSK1 whose activity is reduced ~5-fold. GSK429286A is a more selective ROCK2 inhibitor than the widely utilized ROCK inhibitor Y-27632 as assessed on kinase-specificity panel, and does not significantly inhibit LRRK2 even at doses as high as 30 μM (500-fold higher than IC₅₀ of inhibition of ROCK2). GSK429286A slightly inhibits RSK and p70S6K with IC₅₀ of 0.78 μM and 1.94 μM, respectively. GSK429286A significantly inhibits rat aortic ring dilation with IC₅₀ of 190 nM^[2]. In Vivo:GSK429286A has 61% oral bioavailability in male Sprague-Dawley rats. Oral administration of GSK429286A at single doses of 3-30 mg/kg dramatically reduces mean arterial pressure in the spontaneously hypertensive rats (SHRs) in a dose-dependent manner, with a maximum decrease of 50 mmHg after approximately 2 hours treatment at dose of 30 mg/kg^[1].