BQU57
目录号 : GC10612
An inhibitor of RalA and RalB
Cas No.:1637739-82-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| 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. | |
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.
| Cas No. | 1637739-82-2 | SDF | |
| 化学名 | 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 | ||
| 分子式 | C16H13F3N4O | 分子量 | 334.30 |
| 溶解度 | ≥ 16.55mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。