Item no. |
S1474-50 |
Manufacturer |
Selleckchem
|
CASRN |
864082-47-3 |
Amount |
50 mg |
Category |
|
Type |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
RHO-15 |
Similar products |
GSK429286A |
Available |
|
Administration |
Oral gavage |
Animal Models |
Male spontaneously hypertensive rats (SHRs) |
Chemical Name |
N-(6-fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-4-(4-(trifluoromethyl)phenyl)-1, 4, 5, 6-tetrahydropyridine-3-carboxamide |
Description |
GSK429286A is a selective inhibitor of ROCK1 and ROCK2 with IC50 of 14 nM and 63 nM, respectively. |
Dosages |
ca.30 mg/kg |
Features |
More selective than Y-27632. |
Formulation |
Formulated in 6% Hydroxypropyl-beta-Cyclodextrin (pH4.0) and 5% DMSO solution |
IC50 |
14 nM [1], 14 nM [1], 14 nM [1], 14 nM [1], 14 nM [1], 14 nM [1] |
In vitro |
GSK429286A slightly inhibits RSK and p70S6K with IC50 of 0.78 uM and 1.94 uM, respectively. GSK429286A significantly inhibits rat aortic ring dilation with IC50 of 190 nM. [1] GSK429286A at 1 uM 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 ca.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 uM (500-fold higher than IC50 of inhibition of ROCK2). Like GSK269962A but not sunitinib, GSK429286A treatment at 10 uM ablates basal or G14V-Rho mutant induced phosphorylation of MYPT at Thr850 in HEK-293 cells to a similar extent as H-1152 and Y-27632, consistent with ROCK mediating this phosphorylation, whereas GSK429286A does not inhibit ERM protein phosphorylation either in the presence or absence of G14V-Rho. [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] |
Kinase Assay |
ROCK1 kinase assays, GSK429286A is dissolved at 10 mM in 100% DMSO, with subsequent serial dilution in 100% DMSO. ROCK1 inhibitor activity is determined using human recombinant His-tag ROCK1 kinase domain (amino acid 2-543) expressed in Sf9 cells. Assays of ROCK1 activity are performed in opaque, white walled, 384 well plates, in a total assay volume of 20 uL. The assays contain: 1 nM hROCK1, 1 uM biotinylated peptide (biotin-Ahx-AKRRRLSSLRA-CONH2), 1 uM ATP, 1.85 kBq per well ATP(gamma-33P), 25 mM Hepes pH 7.4, 15 mM MgCl2, 0.015% BSA, increasing concentrations of GSK429286A ranging from 50 uM to 0.8 nM. The reactions are incubated at 22C for 120 minutes, and then terminated by the addition of a 50 uL solution containing 60 mM EDTA and streptavidin PVT SPA beads. The SPA beads are added to a concentration of 0.14 mg per well. The plates are allowed to incubate at 22C for 10 minutes before centrifugation at 1500 rpm for 1 minute. P33 incorporation is quantified by scintillation counting in a Packard TopCount. IC50 value is calculated by bespoke curve fitting software. |
Molecular Weight (MW) |
432, 37 |
Picture ChemicalStructure Description |
GSK429286A Chemical Structure |
Solubility (25C) |
DMSO 87 mg/mL, Water <1 mg/mL, Ethanol 4 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.
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