CTX1
目录号 : GC32911
CTX1是一种新型小分子p53激活剂。
Cas No.:501935-96-2
Sample solution is provided at 25 µL, 10mM.
CTX1 is a novel small molecule p53 activator.
CTX1 induces significant p53-dependent cell death preferentially in HdmX-expressing cells as compare to cells in which p53 is inactivated by Hdm2 overexpression or p53 is knocked down using p53 targeting shRNA. CTX1 can induce p53 protein levels in the p53 mutant cell line, HT29. It is also found that CTX1 exhibits potent activity (LD50 ~1 μM) as a single agent on primary AML patient samples in a similar fashion to AML cell lines. After 16 hr of treatment with CTX1 in HCT116 p53-wild-type cells there is a decrease in S phase from 23% to 3% while HCT116 p53-null cells exhibit a reduction in S phase from 34% to 28%. The combination of low doses of CTX1 and nutlin-3 leads to a significant enhancement of apoptosis in p53-wildtype, but not p53-null cells[1].
CTX1 even as a single agent significantly enhances the survival of mice in this model system. Mice treated with CTX1 alone or in combination with nutlin-3 has a significantly increased survival time (p<0.0001)[1].
[1]. Karan G, et al. Identification of a Small Molecule That Overcomes HdmX-Mediated Suppression of p53. Mol Cancer Ther. 2016 Apr;15(4):574-582.
Kinase experiment: | Exponentially growing OCI cells cultures are treated with 3 μM CTX1, 8 μM Nutlin and or 15 μM RO-5963 for 4.5 hrs. Whole-cell extracts are generated using modified RIPA lysis buffer 25 mM Tris (pH 8.0), 100 mM NaCl, 0.5 mM EDTA, 0.50% NP-40 and complete protease mixture tablet. Protein extracts (~750 μg) are precleared and immune precipitation is performed using a kit according to the manufacturer's protocol. For the immunoprecipitation, mouse monoclonal anti-p53 and rabbit polyclonal anti-HDMX are used. Immune complexes are then collected, proteins are eluted and subjected to Western blotting with the indicated antibodies[1]. |
Animal experiment: | 6 week old female NOD/SCID/IL2Rγ−/− mice are injected into the tail vein with 5×106 cells primary human AML cells (n=5 per group). Drug treatment is started 2 days after tumor cell injection. Nutlin-3 is given by oral gavage (200 mg/kg) and CTX1 is injected i.p. (30 mg/kg) five days a week for 3 weeks. Flow cytometry is performed on bone marrow cells isolated from the mouse femur using a human specific CD45PE antibody using a cytometer to confirm AML infiltration into the bone marrow[1]. |
References: [1]. Karan G, et al. Identification of a Small Molecule That Overcomes HdmX-Mediated Suppression of p53. Mol Cancer Ther. 2016 Apr;15(4):574-582. | |
| Cas No. | 501935-96-2 | SDF | |
| Canonical SMILES | N#CC1=C(C=CC(N)=C2)C2=NC3=CC(N)=CC=C31 | ||
| 分子式 | C14H10N4 | 分子量 | 234.26 |
| 溶解度 | Soluble 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 | 4.2688 mL | 21.3438 mL | 42.6876 mL |
| 5 mM | 0.8538 mL | 4.2688 mL | 8.5375 mL |
| 10 mM | 0.4269 mL | 2.1344 mL | 4.2688 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。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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