RKI-1447Potent ROCK1/ROCK2 inhibitor CAS# 1342278-01-6 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1342278-01-6 | SDF | Download SDF |
| PubChem ID | 60138149 | Appearance | Powder |
| Formula | C16H14N4O2S | M.Wt | 326.37 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 50 mg/mL (153.20 mM) H2O : < 0.1 mg/mL (insoluble) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 1-[(3-hydroxyphenyl)methyl]-3-(4-pyridin-4-yl-1,3-thiazol-2-yl)urea | ||
| SMILES | C1=CC(=CC(=C1)O)CNC(=O)NC2=NC(=CS2)C3=CC=NC=C3 | ||
| Standard InChIKey | GDVRVPIXWXOKQO-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C16H14N4O2S/c21-13-3-1-2-11(8-13)9-18-15(22)20-16-19-14(10-23-16)12-4-6-17-7-5-12/h1-8,10,21H,9H2,(H2,18,19,20,22) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | RKI-1447 is a potent inhibitor of ROCK1 and ROCK2 with IC50 values of 14.5 nM and 6.2 nM, respectively. | |||||
| Targets | ROCK1 | ROCK2 | ||||
| IC50 | 14.5 nM | 6.2 nM | ||||
RKI-1447 Dilution Calculator
RKI-1447 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 3.064 mL | 15.32 mL | 30.6401 mL | 61.2801 mL | 76.6002 mL |
| 5 mM | 0.6128 mL | 3.064 mL | 6.128 mL | 12.256 mL | 15.32 mL |
| 10 mM | 0.3064 mL | 1.532 mL | 3.064 mL | 6.128 mL | 7.66 mL |
| 50 mM | 0.0613 mL | 0.3064 mL | 0.6128 mL | 1.2256 mL | 1.532 mL |
| 100 mM | 0.0306 mL | 0.1532 mL | 0.3064 mL | 0.6128 mL | 0.766 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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RKI-1447 is a potent inhibitor of ROCK 1 and 2 (Rho-associated protein kinase 1 and 2).
ROCK is a serine-threonine kinase, which regulates cell shape and movement via acting on cytoskeleton.
RKI-1447 specifically and dose-dependently inhibits ROCK1 and ROCK2. RKI-1447 inhibited the phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human cancer cells. However, it does not affect the phosphorylation of the AKT, MEK, and S6 kinase at a high concentrations of 10 μmol/L. It indicated a high specificity. Additionally, it was also observed that RKI-1447 selectively suppressed ROCK-mediated cytoskeleton re-organization following LPA stimulation, but does not affect PAK-meditated lamellipodia and filopodia formation following PDGF and Bradykinin stimulation. RKI-1447 inhibited migration, invasion and anchorage-independent tumor growth of breast cancer cells [1]
In mouse model, tumors were monitored at the time of tumor onset and the beginning of treatment (once a day for 14 days) with vehicle (20% HPCD) or RKI-1447 (200 mg/kg/day), when tumor volumes reached 75 to 2,300 mm3. Tumors from mice treated with vehicle increased in average tumor volume of 68.3% but tumors from mice treated with the RKI-1447 increased in average tumor volume of only 8.8%. Thus, RKI-1447 inhibited mammary tumor growth by 87% [1].
Reference:
[1] Patel R A et al. , RKI-1447 Is a Potent Inhibitor of the Rho-Associated ROCK Kinases with Anti-Invasive and Antitumor Activities in Breast Cancer. Cancer Res, 2012, 72(19): 5025-5034.
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RKI-1447 is a potent inhibitor of the Rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer.[Pubmed:22846914]
Cancer Res. 2012 Oct 1;72(19):5025-34.
The Rho-associated kinases ROCK1 and ROCK2 are critical for cancer cell migration and invasion, suggesting they may be useful therapeutic targets. In this study, we describe the discovery and development of RKI-1447, a potent small molecule inhibitor of ROCK1 and ROCK2. Crystal structures of the RKI-1447/ROCK1 complex revealed that RKI-1447 is a Type I kinase inhibitor that binds the ATP binding site through interactions with the hinge region and the DFG motif. RKI-1447 suppressed phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human cancer cells, but had no effect on the phosphorylation levels of the AKT, MEK, and S6 kinase at concentrations as high as 10 mumol/L. RKI-1447 was also highly selective at inhibiting ROCK-mediated cytoskeleton re-organization (actin stress fiber formation) following LPA stimulation, but does not affect PAK-meditated lamellipodia and filopodia formation following PDGF and Bradykinin stimulation, respectively. RKI-1447 inhibited migration, invasion and anchorage-independent tumor growth of breast cancer cells. In contrast, RKI-1313, a much weaker analog in vitro, had little effect on the phosphorylation levels of ROCK substrates, migration, invasion or anchorage-independent growth. Finally, RKI-1447 was highly effective at inhibiting the outgrowth of mammary tumors in a transgenic mouse model. In summary, our findings establish RKI-1447 as a potent and selective ROCK inhibitor with significant anti-invasive and antitumor activities and offer a preclinical proof-of-concept that justify further examination of RKI-1447 suitability as a potential clinical candidate.
