Home>>Signaling Pathways>> Cell Cycle/Checkpoint>> ROCK>>GSK269962A

GSK269962A (Synonyms: GSK269962A, GSK269962B)

Catalog No.GC17936

ROCK inhibitor

Products are for research use only. Not for human use. We do not sell to patients.

GSK269962A Chemical Structure

Cas No.: 850664-21-0

Size Price Stock Qty
10mg
$111.00
In stock
50mg
$506.00
In stock

Tel:(909) 407-4943 Email: sales@glpbio.com

Customer Reviews

Based on customer reviews.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Kinase experiment:

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].

Animal experiment:

Rats[1] Male Sprague-Dawley rats (350-400g) are anesthetized with 5% isoflurane in O2 and killed by exsanguination. Aortic rings, approximately 2 to 3 mm in length, are suspended by two 0.1-mm diameter tungsten wire hooks in 10 mL tissue baths containing Krebs of the following composition: 112 mM NaCl, 4.7 mM KCl, 2.5 mM CaCl2, 1.2 mM KH2PO2, 1.2 mM MgSO4, 25 mM NaHCO3, 11.0 mM dextrose, 0.01 mM indomethacin, and 0.01 mM L-NAME. Krebs is maintained at 37°C and aerated with 95% O2, 5% CO2, pH 7.4,. Changes in isometric force are measured under optimal resting tension (1 g) using FT03 force-displacement transducers coupled to model 7D polygraphs. After a 60-min equilibration period, the vessels are treated with standard concentrations of KCl (60 mM) and phenylephrine (1 μM). Cumulative concentration-response curves to phenylephrine are obtained for each tissue by dosing at 0.5-log unit intervals (1 nM to 10 μM). After several washes, each vessel is contracted to equilibrium with an EC80 concentration of phenylephrine, and tone is reversed by adding cumulative amounts of either GSK269962A or SB-772077-B at 0.5-log unit intervals (0.1 nM to 1 μM). Responses are expressed as percentage reversal of the tone established with phenylephrine.

References:

[1]. Doe C, et al. Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98.

Background

GSK269962A is a potent ROCK inhibitor with IC50s of 1.6 and 4 nM for recombinant human ROCK1 and ROCK2 respectively.

GSK269962A IC50 values of 1.6 nM toward recombinant human ROCK1. GSK269962A also exhibits more than 30-fold selectivity against a panel of serine/threonine kinases. GSK269962A induces vasorelaxation in preconstricted rat aorta with an IC50 of 35 nM. Both are highly potent toward human ROCK1 with IC50 of 1.6 nM for GSK269962A. On the other hand, GSK269962A has a significantly improved kinase selectivity profile with at least >30-fold selectivity against the panel of protein kinase tested[1].

Oral administration of GSK269965A (0.3, 1, and 3 mg/kg) induces a dose-dependent reduction in blood pressure in spontaneously hypertensive rat (SHR). The reduction of blood pressure is acute and substantial. The maximal effect on blood pressure is observed approximately 2 h after oral gavages for both compounds. Under a similar setting, oral administration of Y-27632 (10 and 30 mg/kg) also induced a dose-dependent decrease of blood pressure. For all three Rho kinase inhibitors, the reduction of blood pressure is accompanied by an acute, dose-dependent increase in heart rate, presumably due to the activation of baroreflex mechanism[1].

References:
[1]. Doe C, et al. Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities. J Pharmacol Exp Ther. 2007 Jan;320(1):89-98.

Chemical Properties

Cas No. 850664-21-0 SDF
Synonyms GSK269962A, GSK269962B
Chemical Name N-[3-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethylimidazo[4,5-c]pyridin-6-yl]oxyphenyl]-4-(2-morpholin-4-ylethoxy)benzamide
Canonical SMILES CCN1C2=CC(=NC=C2N=C1C3=NON=C3N)OC4=CC=CC(=C4)NC(=O)C5=CC=C(C=C5)OCCN6CCOCC6
Formula C29H30N8O5 M.Wt 570.6
Solubility DMF: 16 mg/ml,DMF:PBS(pH7.2) (1:2): 0.3 mg/ml,DMSO: 14 mg/ml Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Reviews

Review for GSK269962A

Average Rating: 5 ★★★★★ (Based on Reviews and 8 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for GSK269962A

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.