BQU57 |
| Catalog No.GC10612 |
BQU57 muestra una inhibiciÓn selectiva de Ral en relaciÓn con Ras o Rho e inhibe el crecimiento tumoral del xenoinjerto de manera similar al agotamiento de Ral por siRNA. El IC50 para BQU57 de 2,0 μM en H2122 y 1,3 μM en H358.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1637739-82-2
Sample solution is provided at 25 µL, 10mM.
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BQU57 is a derivative of RBC8. It show selectivity for Ral relative to the GTPases Ras and RhoA and inhibit tumour xenograft growth. The binding of BQU57 to RalB–GDP was with a dissociation constant (Kd) of 7.760.6 mM by using isothermal titration calorimetry (ITC). It was similar to the results from surface plasmon resonance (SPR), which had a Kd value of 4.761.5 mM 1.
RBC8 or BQU57 can effectively inhibited the colony formation in soft agar of the Ral-dependent lines H2122 and H358, but not H460 or Calu-6. The IC50 value of RBC8 was 3.5 mM in H2122 cells and 3.4 mM in H358 cells; and the IC50 value of BQU57 was 2.0 mM in H2122 cells and 1.3 mM in H358 cells. RBC8 or BQU57 treatment showed no further inhibition of colony formation after RAL knockdown 1.
RBC8 and BQU57 acted specifically through the GDP-bound form of Ral proteins. RBC8 and BQU57 inhibited both Ral A and Ral B activation in both the H2122 and H358 cell lines by a Ral pull-down assay using RALBP1-bound agarose beads 1.
The inhibition of Ral activity and tumour growth by these compounds were evaluated in human lung cancer xenografts in mice. RBC8 and BQU57 showed good properties in vivo. RBC8 and BQU57 entry into tumour tissue 3 h after dosing, and were detectable in tumour tissue 1. BQU57 (10, 20 and 50mg per kg bodyweight) was intraperitoneal injected into H2122 tumour xenografts, and the activation of Ral in tumour extracts was analysed in RALBP1 pull-down assays. Both RalA and RalB were inhibited by RBC8 and BQU57. But no inhibition of Ras or RhoA activity was happened 1.
References:
1. Yan C, Liu D, Li L et al. Discovery and characterization of small molecules that target the GTPase Ral. Nature. 2014 Nov 20;515(7527):443-7.
| Kinase experiment [1]: | |
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RalA ELISA. |
This assay used J82 human bladder cancer cells that stably expressed Flag-tagged RalA. The Flag epitope tag greatly increased the sensitivity and dynamic range of the assay compared with using Ral-specific antibodies for detection. Cells were treated with each of the 88 compounds (tested at 50 mM), and then extracts were prepared. The binding of Flag–RalA to recombinant RALBP1 that had been immobilized in 96-well plates was quantified. In this assay, RalA binding reflects Ral’s GTP loading and capacity for effector activation. |
| Cell experiment [1]: | |
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Cell lines |
Human lung cancer cell lines (H2122, H358) |
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Preparation method |
Soluble in DMSO > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
2-4 weeks at 37oC |
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Applications |
BQU57 acts specifically through the GDP-bound form of Ral proteins. Ral-dependent lines H2122 and H358 are sensitive to treatment with BQU57. BQU57 treatment exhibits no further inhibition of colony formation after RAL knockdown. |
| Animal experiment [1]: | |
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Animal models |
H2122 tumor xenografts (median size, 250 mm3) |
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Dosage form |
Single intraperitoneal injection of BQU57 (10, 20 and 50 mg per kg body weight) |
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Applications |
BQU57 shows a dose-dependent (10, 20 and 50 mg per kg body weight per day) growth inhibition in the mice. Both RalA and RalB were blocked by BQU57. |
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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. Yan C, Liu D, Li L et al. Discovery and characterization of small molecules that target the GTPase Ral. Nature. 2014 Nov 20;515(7527):443-7. | |
| Cas No. | 1637739-82-2 | SDF | |
| Chemical Name | 6-amino-1,3-dimethyl-4-(4-(trifluoromethyl)phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile | ||
| Canonical SMILES | CC1=NN(C)C(OC(N)=C2C#N)=C1C2C3=CC=C(C(F)(F)F)C=C3 | ||
| Formula | C16H13F3N4O | M.Wt | 334.3 |
| Solubility | ≥ 16.55mg/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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9913 mL | 14.9566 mL | 29.9133 mL |
| 5 mM | 0.5983 mL | 2.9913 mL | 5.9827 mL |
| 10 mM | 0.2991 mL | 1.4957 mL | 2.9913 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
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
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 15 reference(s) in Google Scholar.)
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