GSK429286A|Selective ROCK1/ROCK2 inhibitor|CAS# 864082-47-3

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Size	Price	Stock
10mM (in 1mL DMSO)	$88.00	In stock
5mg	$80.00	In stock
25mg	$240.00	In stock
100mg	$600.00	In stock

Publications citing ApexBio Products

Nature.
2017 Jan 19;541(7637):417-420.

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2016 Apr 21;532(7599):398-401.

Science.
2016 Aug 5;353(6299)594-8

Nature Biotechnology.
2017 Jun;35(6):569-576

Cell.
2017 Apr 6;169(2):286-300.

Cell.
2015 Aug 27;162(5):987-1002.

Cell.
2015 Feb 12;160(4):729-44.

Nature Medicine.
2017 Apr;23(4):493-500.

Cancer Cell.
2017 May 8;31(5):635-652.e6.

Immunity.
2016 Jan 19;44(1):88-102

Nat Cell Biol.
2015 May;17(5):627-38.

Nat Immunol.
2017 Jun;18(6):654-664.

Nat Neurosci.
2015 Oct;18(10):1464-73.

Cell Res.
2016 Sep;26(9):1007-20.

Mol Cell.
2017 May 18;66(4):546-557.

Mol Cell.
2017 Jun 1;66(5):698-710.

Mol Cell.
2017 Mar 2;65(5):941-955.e8.

Nat Commun.
2016 Feb 1;7:10492.

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2016 Apr 11;213(1):109-25.

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2016 Jul 13;20(1):13-24.

Proc Natl Acad Sci U S A.
2016 Mar 8;113(10):2585-90.

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2015 Jun 30;112(26):E3365-73.

Proc Natl Acad Sci U S A.
2015 Jul 28;112(30):9412-7.

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2016 Jul 2;12(7):1129-52.

Cancer Res canres.
2946.2015.

Elife.
2016 Jan 14;5. pii: e12203.

Nucleic Acids Res.
2016 Feb 18;44(3):e2.

EMBO Rep.
2015 Sep;16(9):1114-30.

Oncogene.
2016 Mar 21.

Cell Rep.
2015 Sep 29;12(12):1986-96.

Cell Death Differ.
2016 Jun;23(6):1026-37.

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Quality Control

Quality Control & MSDS

View current batch:

Purity = 99.10%

Chemical structure

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.
Reaction Conditions	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
Applications	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.

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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	>21.6mg/mL in DMSO	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.