GSK269962A HCl

Catalog No.S7687 Batch:S768701

Technical Data

Formula	C₂₉H₃₀N₈O₅.HCl
Molecular Weight	607.06	CAS No.	2095432-71-4
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (164.72 mM)
		Ethanol	6 mg/mL (9.88 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

GSK269962A HCl is a selective ROCK(Rho-associated protein kinase) inhibitor with IC50 values of 1.6 and 4 nM for ROCK1 and ROCK2, respectively.

Targets

ROCK1 ^[1] (Cell-free assay)	ROCK2 ^[1] (Cell-free assay)	MSK1 ^[1] (Cell-free assay)	RSK1 ^[1] (Cell-free assay)
1.6 nM	4 nM	49 nM	132 nM

In vitro

GSK269962A completely abolished the actin stress fiber formation induced by angiotensin II in human smooth muscles. Such suppressive effect on actin fiber formation was observed beginning at around 1 μM GSK269962A. GSK269962A induced vasorelaxation in preconstricted rat aorta(tissue baths) with an IC50 of 35 nM. the relaxation induced by GSK269962A is reversible. GSK269962A suppressed IL-6 mRNA transcription and reduced LPS-induced IL-6 and TNF-α protein production in macrophages^[1].

In vivo

Oral administration of GSK269962A produced a profound dose-dependent reduction of systemic blood pressure in spontaneously hypertensive rats. The reduction of blood pressure was acute and substantial. The maximal effect on blood pressure was observed approximately 2 h after oral gavages. The reduction of blood pressure was accompanied by an acute, dose-dependent increase in heart rate, presumably due to the activation of baroreflex mechanism^[1]. ROCK inhibition with the use of GSK 269962 in the 10 mg/kg dose, in turn, triggered an increase in VV(voided volume), PVR(post-void residual), VT(volume threshold), VE(voiding efficiency), ICI(intercontraction interval), BC(bladder compliance), and VTNVC(volume threshold to elicit NVC). The inhibition of the ROCK pathway through GSK 269962 appeared to have no effect on either HR(heart rate), SBP(systolic blood pressure), MBP(systolic blood pressure), or DBP(diastolic blood pressure)^[2]. NVC:nonvoiding contractions.

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Human primary smooth muscle cells Concentrations 3 μM Incubation Time 150 min Method Human primary smooth muscle cells were serum-starved(cells were grown on coverslips, and at approximately 50% confluence, they were serum-starved overnight) and stimulated with AngII (100 nM) for 2 h. ROCK inhibitors (3 μM for SB-772077-B or GSK269962A) were added 30 min before AngII stimulation, and cells were fixed and stained with rhodamine phalloidin. Confocal images of actin stain were obtained.
Animal Study:^{^[2]}	Animal Models female Wistar rats Dosages 5 or 10 mg/kg Administration intra-arterially

Cell Assay:^{^[1]}

Cell lines
Human primary smooth muscle cells
Concentrations
3 μM
Incubation Time
150 min
Method
Human primary smooth muscle cells were serum-starved(cells were grown on coverslips, and at approximately 50% confluence, they were serum-starved overnight) and stimulated with AngII (100 nM) for 2 h. ROCK inhibitors (3 μM for SB-772077-B or GSK269962A) were added 30 min before AngII stimulation, and cells were fixed and stained with rhodamine phalloidin. Confocal images of actin stain were obtained.

Animal Study:^{^[2]}

Animal Models
female Wistar rats
Dosages
5 or 10 mg/kg
Administration
intra-arterially

References

Selleck's GSK269962A HCl has been cited by 6 publications

Keratin isoform shifts modulate motility signals during wound healing [ bioRxiv, 2023, 2023.05.04.538989]	PubMed: 37205459
The Meningioma Enhancer Landscape Delineates Novel Subgroups and Drives Druggable Dependencies [ Cancer Discov, 2020, CD-20-0160]	PubMed: 32703768
Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration [ Elife, 2020, 9:e58165]	PubMed: 32705984
Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications. [ Nat Commun, 2019, 10(1):1333]	PubMed: 30902996
B. anthracis Lethal Toxin but not Edema Toxin, Increases Pulmonary Artery Pressure and Permeability in Isolated Perfused Rat Lungs [Cui X Am J Physiol Heart Circ Physiol, 2019, 10.1152/ajpheart.00685.2018]	PubMed: 30767685
CTGF/VEGFA-activated Fibroblasts Promote Tumor Migration Through Micro-environmental Modulation [ Mol Cell Proteomics, 2018, 17(8):1502-1514]	PubMed: 29669735

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SHIPPING AND STORAGE
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