GSK429286A
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 432.37 |
| Cas No. | 864082-47-3 |
| Formula | C21H16F4N4O2 |
| Solubility | ≥21.6mg/mL in DMSO, ≥2.73 mg/mL in EtOH with ultrasonic and warming,insoluble in H2O |
| Chemical Name | N-(6-fluoro-1H-indazol-5-yl)-6-methyl-2-oxo-4-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-pyridine-5-carboxamide |
| SDF | Download SDF |
| 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 |
| Shipping Condition | Evaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request. |
| General tips | For obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. |
| 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. |
|
| 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 | ||||
Quality Control & MSDS
- View current batch:
Chemical structure
