GSK429286A

GSK429286A is a selective inhibitor of ROCK1 with an IC50 value of 14 nM.

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

Signaling Pathways >> Stem Cell/Wnt >> ROCK

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

Research Areas >> Cancer

ROCK1:14 nM (IC50)

RSK:780 nM (IC50)

p70S6K:1940 nM (IC50)

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].

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].

Rats: Spontaneously hypertensive rats (SHRs) are treated with GSK429286A to establish its effect on mean arterial pressure. Compound is administered by single dose oral gavage (3, 10, 30 mg/kg)[1].

[1]. Goodman KB et al Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors. J Med Chem. 2007 Jan 11;50(1):6-9.

[2]. Nichols RJ et al Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease. Biochem J. 2009 Oct 23;424(1):47-60.

Y-27632 2HCl | Fasudil Hydrochloride | KD025(SLx-2119) | Narciclasine | Y-39983 HCl | Thiazovivin | GSK180736A | GSK 269962 | SR-3677 | TC-S 7001 | K-115 | RKI-1447 | LX7101 | Chroman 1 | H-1152 (dihydrochloride)