Search Site
Related Products
GSK429286ASelective ROCK1/ROCK2 inhibitor

GSK429286A

Catalog No. A5611
Size Price Stock Qty
10mM (in 1mL DMSO) $88.00 In stock
5mg $80.00 In stock
25mg $240.00 In stock
100mg $600.00 In stock

Tel: +1-832-696-8203

Email: sales@apexbt.com

Worldwide Distributors

Sample solution is provided at 25 µL, 10mM.

Quality Control

Quality Control & MSDS

View current batch:

Chemical structure

GSK429286A

Biological Activity

Description GSK429286A is a selective inhibitor of ROCK1 and ROCK2 with IC50 values of 14 nM and 63 nM, respectively.
Targets ROCK1 ROCK2        
IC50 14 nM 63 nM        

Protocol

Cell experiment: [1]

Cell lines

MDA-MB-231 (TRPM7 shRNA) cells and MCF7 (TRPM7 shRNA) cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reacting condition

1 μM, 24 hours

Applications

GSK429286A caused Rho-kinase inhibition restored serum-induced transwell migration of TRPM7 knockdown cells without affecting MDA-MB-231 control cell migration. Likewise, gap-closure speed of MFC7 TRPM7 shRNA cells was rescued by Rho-kinase inhibition. In contrast to MDA- MB-231 cells, low concentrations of GSK429286A significantly increased gap-closure speed of MCF7 control cells.

Animal experiment: [2]

Animal models

Male Sprague-Dawley rats

Dosage form

Oral gavage, 30 mg/kg

Application

GSK429286A with 61% oral bioavailability, dramatically reduced mean arterial pressure in spontaneously hypertensive rats after oral administration dose-dependently. A maximum decrease of 50 mmHg was observed approximately 2 h after oral administration at 30 mg/kg.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Middelbeek J, Kuipers A J, Henneman L, et al. TRPM7 is required for breast tumor cell metastasis. Cancer research, 2012, 72(16): 4250-4261.

[2] Goodman K B, Cui H, Dowdell S E, et al. Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors. Journal of medicinal chemistry, 2007, 50(1): 6-9.

GSK429286A Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

GSK429286A Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Chemical Properties

Cas No. 864082-47-3 SDF Download SDF
Chemical Name N-(6-fluoro-1H-indazol-5-yl)-6-methyl-2-oxo-4-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-pyridine-5-carboxamide
Canonical SMILES CC1=C(C(CC(=O)N1)C2=CC=C(C=C2)C(F)(F)F)C(=O)NC3=C(C=C4C(=C3)C=NN4)F
Formula C21H16F4N4O2 M.Wt 432.37
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Background

GSK429286A is a selective inhibitor of ROCK1 and ROCK2 with IC50 value of 14 nM and 63 nM, respectively [1].

Rho-kinase (ROCK) is a member of AGC (protein kinase A, protein kinase G and protein kinase C) family and plays an important role in promoting actin-myosin-mediated contractile force generation [2].

GSK429286A is a potent ROCK inhibitor and has a different activity with the reported ROCK inhibitor Y27632. Using GST method, it is shown that GSK429286A treatment (10 μM) increased MYPT phosphrylation at Thr850 via inhibiting ROCK which mediated this phosphorylation process [3].

In male Sprague-Dawley rat model with spontaneously hypertensive, oral administration of GSK429286A (30 mg/kg) marks reduced mean arterial pressure and the maximum decreased was as 50 mmHg after nearly 2 h treatment [4].

References:
[1].  Nichols, R.J., et al., Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease. Biochem J, 2009. 424(1): p. 47-60.
[2].  Shi, J., et al., Distinct roles for ROCK1 and ROCK2 in the regulation of cell detachment. Cell Death Dis, 2013. 4: p. e483.
[3].  Davis, D.A., et al., Increased therapeutic potential of an experimental anti-mitotic inhibitor SB715992 by genistein in PC-3 human prostate cancer cell line. BMC Cancer, 2006. 6: p. 22.
[4].   Goodman, K.B., et al., Development of dihydropyridone indazole amides as selective Rho-kinase inhibitors. J Med Chem, 2007. 50(1): p. 6-9.