1. Cell Cycle/DNA Damage
    TGF-beta/Smad
    Stem Cell/Wnt
  2. ROCK

GSK269962A (Synonyms: GSK 269962)

Cat. No.: HY-15556 Purity: 98.01%
Handling Instructions

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

For research use only. We do not sell to patients.

GSK269962A Chemical Structure

GSK269962A Chemical Structure

CAS No. : 850664-21-0

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 121 In-stock
Estimated Time of Arrival: December 31
5 mg USD 96 In-stock
Estimated Time of Arrival: December 31
10 mg USD 180 In-stock
Estimated Time of Arrival: December 31
50 mg USD 720 In-stock
Estimated Time of Arrival: December 31
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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

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

IC50 & Target[1]

ROCK1

1.6 nM (IC50)

ROCK2

4 nM (IC50)

RSK1

132 nM (IC50)

MSK1

49 nM (IC50)

AKT1

955 nM (IC50)

AKT2

1350 nM (IC50)

AKT3

1510 nM (IC50)

CDK2

3500 nM (IC50)

GSK3α

1260 nM (IC50)

In Vitro

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].

In Vivo

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].

Solvent & Solubility
In Vitro: 

DMSO : ≥ 30 mg/mL (52.58 mM)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 1.7525 mL 8.7627 mL 17.5254 mL
5 mM 0.3505 mL 1.7525 mL 3.5051 mL
10 mM 0.1753 mL 0.8763 mL 1.7525 mL
*Please refer to the solubility information to select the appropriate solvent.
References
Kinase Assay
[1]

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

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.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

570.60

Formula

C₂₉H₃₀N₈O₅

CAS No.

850664-21-0

SMILES

CCN1C2=CC(OC3=CC=CC(NC(C4=CC=C(OCCN5CCOCC5)C=C4)=O)=C3)=NC=C2N=C1C6=NON=C6N

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Purity: 98.01%

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Product Name:
GSK269962A
Cat. No.:
HY-15556
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GSK269962A

Cat. No.: HY-15556