| Name | GSK269962A |
| Description | GSK269962A (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. |
| Cell Research | 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.(Only for Reference) |
| Kinase Assay | The enzyme activity and kinetics of the purified ROCK1(3-543) are determined using scintillation proximity assay. In this assay, purified ROCK1 is incubated with peptide substrate (Biotin-Ahx-AKRRLSSLRA-CONH2), and 33ATP and the subsequent incorporation of 33P into the peptide is quantified by streptavidin bead capture. For IC50 determination, test compounds are dissolved at 10 mM in 100% DMSO, with subsequent serial dilution in 100% DMSO. Compounds are typically assayed over an 11-point dilution range with a concentration in the assay of 10 μM to 0.2 nM in 3-fold dilutions. For dose-response curves, data are normalized and expressed as percentage inhibition using the formula 100×[(U-C1)/(C2-C1)], where U is the unknown value, C1 is the average of the high signal (0%) control wells, and C2 is the average of the low signal (100%) control wells. Curve fitting is performed The results for each compound are recorded as pIC50 values[1]. |
| 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 |
| 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. 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). |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 6 mg/mL (9.88 mM)
DMSO : 57.1 mg/mL (100 mM)
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| Keywords | anti-inflammatory | ROCK | pressure | blood | GSK269962A | antihypertensive | Rho-associated protein kinase | GSK269962 | Inhibitor | Rho-associated kinase | GSK-269962 | ROK | ROCK2 | inhibit | GSK-269962A | vasodilatory | Rho-kinase | ROCK1 | cardiovascular |
| Inhibitors Related | GSK180736A | SAR407899 hydrochloride | RKI-1447 | Bimiralisib | Belumosudil | Fasudil hydrochloride | Y-27632 dihydrochloride | Tofacitinib | Y-27632 | ROCK-IN-5 | Thiazovivin | Sodium salicylate |
| Related Compound Libraries | Anti-Lung Cancer Compound Library | Bioactive Compound Library | Pain-Related Compound Library | Kinase Inhibitor Library | Inhibitor Library | Anti-Prostate Cancer Compound Library | Anti-Aging Compound Library | Bioactive Compounds Library Max | Anti-Liver Cancer Compound Library | TGF-beta/Smad Compound Library |
United States
