| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
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| Targets |
ROCK1 14.5 nM (IC50) ROCK2 6.2 nM (IC50) Apoptosis
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|---|---|
| ln Vitro |
In human cancer cells, RKI 1447 inhibits the phosphorylation of the ROCK substrates MLC-2 and MYPT-1, but at doses as high as 10 μM, it had no influence on the phosphorylation levels of AKT, MEK, and S6 kinase[1]. (0.003-10 μM) is effective in preventing human cancer cells' phosphorylation of the ROCK substrates MLC-2 and MYPT-1[1]. Effective anticancer efficacy against colorectal carcinoma (CRC) is demonstrated by RKI 1447. HCT-8 and HCT-116 cell growth is significantly suppressed by RKI 1447 (10-320 μM; 24 hours)[2]. A dose-dependent manner of inducing apoptosis is observed with RKI 1447 (20-80 μM; 24 hours)[2].
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| ln Vivo |
The growth of breast tumors is inhibited in vivo by RKI 1447 (200 mg/kg; intraperitoneal; daily for 14 days)[1]. On CRC in vivo, RKI 1447 (100 mg/kg; ip; once every 3 days; for 14 days) exhibits anticancer efficacy. The mice are not physiologically harmed by RKI 1447[2].
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: CRC cell lines HCT-8 and HCT-116 cells Tested Concentrations: 0, 10, 20, 40, 80, 160, 320 μM Incubation Duration: 24 hrs (hours) Experimental Results: HCT-8 and HCT-116 viability was drastically diminished in a dose-dependent manner. Apoptosis Analysis[2] Cell Types: CRC cell lines HCT-8 and HCT-116 cells Tested Concentrations: 0, 20, 40, 80 μM Incubation Duration: 24 hrs (hours) Experimental Results: Treatment promoted apoptosis. Western Blot Analysis[1] Cell Types: MDA-MB-231 human breast cancer cells Tested Concentrations: 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3,10 μM Incubation Duration: Experimental Results: diminished the levels of P-MLC-2, but not total MLC-2, in a concentration-dependent manner with significant effects starting at 100 nM. |
| Animal Protocol |
Animal/Disease Models: MMTV/neu transgenic mice [FVB/N-Tg (MMTVneu) 202 Mul/J][1]
Doses: 200 mg/kg Route of Administration: Treated ip daily for 14 days Experimental Results: Tumors from mice treated with vehicle increased in size with an average percent change in tumor volume of 68.3%. In contrast, tumors from mice treated with the RKI-1447 increased in size with an average percent change in tumor volume of only 8.8%. Thus, RKI-1447 inhibited mammary tumor growth by 87%. Animal/Disease Models: 5weeks old Male BALB/C nude mice[2] Doses: 100 mg/kg Route of Administration: intraperitoneally (ip) injected; once every 3 days; for 14 days Experimental Results: Efficiently blocked CRC tumor growth in vivo. |
| References |
[1]. Ronil A Patel, 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 Oct 1;72(19):5025-34.
[2]. Liyi Li, et al. RKI-1447 Suppresses Colorectal Carcinoma Cell Growth via Disrupting Cellular Bioenergetics and Mitochondrial Dynamics. J Cell Physiol. 2020 Jan;235(1):254-266. |
| Molecular Formula |
C16H16CL2N4O2S
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|---|---|
| Molecular Weight |
399.29
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| CAS # |
1782109-09-4
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| Related CAS # |
RKI-1447;1342278-01-6
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| SMILES |
Cl.Cl.S1C=C(C2C=CN=CC=2)N=C1NC(NCC1C=CC=C(C=1)O)=O
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| Solubility (In Vitro) |
DMSO : 50 mg/mL (125.22 mM)
H2O : < 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5044 mL | 12.5222 mL | 25.0445 mL | |
| 5 mM | 0.5009 mL | 2.5044 mL | 5.0089 mL | |
| 10 mM | 0.2504 mL | 1.2522 mL | 2.5044 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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