RK-33 |
| Catalog No.GC17781 |
DDX3 (a RNA helicase) inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1070773-09-9
Sample solution is provided at 25 µL, 10mM.
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IC50: 4.4-8.4 μM for cancer cell lines with high levels of DDX3 expression (A549, H1299, H23, and H460)
RK-33 is a DDX3 inhibitor.
DDX3 has been identified as a RNA helicase that is overexpressed in various cancer types such as lung cancer and is correlated with lower survival in lung cancer patients.
In vitro: RK-33 was reported to bind to DDX3 and abrogated its activity. Inhibition of DDX3 by RK-33 resulted in G1 cell cycle arrest, induced apoptosis, and promoted radiation sensitization in DDX3-overexpressing cells. Moreover, the loss of DDX3 function caused by RK-33 impaired Wnt signaling via disruption of the DDX3-β-catenin axis [1].
In vivo: The effect of RK-33 with a fractional dosing regimen was studied in the Twist1/KrasG12D lung cancer model. Results showed that during the 3 weeks treatment, a modest decrease in tumor growth with radiation and even more so with the combination of RK-33 and radiation. Therefore, these data indicated that RK-33 in combination with hypofractionated radiation was able to decrease lung tumor load effectively in preclinical lung cancer models and performed much better than the commonly used radiosensitizer carboplatin [1].
Clinical trial: Up to now, RK-33 is still in the preclinical development stage.
Reference:
[1] Bol GM et al. Targeting DDX3 with a small molecule inhibitor for lung cancer therapy. EMBO Mol Med. 2015 Mar 27;7(5):648-69.
Cell experiment: | Briefly, 8×102 MCF-7 cells are seeded in a 96-well plate, and treated with different concentrations of RK-33 loaded nanoparticles and unloaded nanoparticles next day. After 72-h incubation, MTS reagent is added to the cells, and the absorbance is measured at 490 nm after 2-h incubation with MTS reagent. The experiment is repeated three independent times. |
Animal experiment: | Mice are randomLy redistributed into four groups of eight according to their tumor growth, which results in an approximately equal distribution of tumor size at the beginning of radiation and RK-33 drug treatment. The four groups of mice are blindly chosen for four different experimental procedures, including control (injection of DMSO only), RK-33 treatment (injection of RK-33 only 50 mg/kg), radiation (one-time radiation of 5 Gy), or radiation and RK-33 treatment (combination of radiation of 5 Gy and RK-33 injection). RK-33 and DMSO are injected intraperitoneally thrice weekly for two weeks. Radiation is performed at the beginning of drug injection using the Small Animal Radiation Research Platform (SARRP) with a circular beam of 1 cm diameter, focusing on the tumor site. Mice of each group are euthanized 0 h and 24 h after radiation and tumors are extracted for γH2AX, cleaved Caspase 3, and Ki67 staining. The remaining mice of each group are imaged with a Xenogen IVIS Spectrum, with injection of D-luciferin 5 minutes before imaging. Mice are euthanized after six weeks of imaging and tumors are extracted for H&E staining, cleaved Caspase 3, and i67 staining. Morphology of the tumors after RK-33 and radiation treatment is assessed by a veterinary pathologist on hematoxylin and eosin stained sections. |
References: [1]. Xie M,et al. RK-33 radiosensitizes prostate cancer cells by blocking the RNA helicase DDX3. Cancer Res. 2016 Sep 12. | |
| Cas No. | 1070773-09-9 | SDF | |
| Chemical Name | 3,7-bis(4-methoxybenzyl)-3,7-dihydro-2H-diimidazo[4,5-d:4',5'-f][1,3]diazepin-2-one | ||
| Canonical SMILES | COC1=CC=C(CN2C=NC3=C2N=CN=C(N4CC5=CC=C(OC)C=C5)C3=NC4=O)C=C1 | ||
| Formula | C23H20N6O3 | M.Wt | 428.44 |
| Solubility | ≥ 21.4mg/mL in DMSO | 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 | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.334 mL | 11.6702 mL | 23.3405 mL |
| 5 mM | 0.4668 mL | 2.334 mL | 4.6681 mL |
| 10 mM | 0.2334 mL | 1.167 mL | 2.334 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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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
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 31 reference(s) in Google Scholar.)
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