GSK429286A |
| カタログ番号GC18119 |
GSK429286A は、14 nM の IC50 値を持つ ROCK1 の選択的阻害剤です。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 864082-47-3
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment: [1] | |
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Cell lines |
MDA-MB-231 (TRPM7 shRNA) cells and MCF7 (TRPM7 shRNA) cells |
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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. |
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Reaction Conditions |
1 μM, 24 hours |
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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] | |
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Animal models |
Male Sprague-Dawley rats |
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Dosage form |
Oral gavage, 30 mg/kg |
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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. |
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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. |
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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. | |
| Cas No. | 864082-47-3 | SDF | |
| Chemical Name | N-(6-fluoro-1H-indazol-5-yl)-6-methyl-2-oxo-4-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1H-pyridine-5-carboxamide | ||
| 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 | ||
| Formula | C21H16F4N4O2 | M.Wt | 432.37 |
| 溶解度 | ≥ 21.6mg/mL in DMSO, ≥ 2.73 mg/mL in EtOH with ultrasonic and warming | 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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3128 mL | 11.5642 mL | 23.1283 mL |
| 5 mM | 0.4626 mL | 2.3128 mL | 4.6257 mL |
| 10 mM | 0.2313 mL | 1.1564 mL | 2.3128 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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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.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 11 reference(s) in Google Scholar.)
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