Nutlin-3
(Synonyms: 4-[[4,5-双(4-氯苯基)-4,5-二氢-2-[4-甲氧基-2-(1-甲基乙氧基)苯基]-1H-咪唑-1-基]羰基]-2-哌嗪酮,Nutlin 3,MDM2 Antagonist) 目录号 : GC16051
A racemic mixture of (?)-nutlin-3 and (+)-nutlin-3
Cas No.:890090-75-2
Sample solution is provided at 25 µL, 10mM.
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Nutlin-3, a tetra-substituted imidazoline, is a potent and selective small-molecule antagonist of murine double minute 2 (MDM2), which occupies the binding site of p53 in MDM2 and consequently prevent MDM2 binding to p53 leading to the disruption of the autoregulator feedback loop and the fostering of the p53 tumor suppressor network. It also binds to murine double minute 4 (MDM4), which is another component of the p35 tumor surveillance pathway. Nutlin-3 is being investigated as an antitumor agent for its antiangiogenic activity in cells through inhibiting endothelial cell migration, inducing cell cycle arrest, and increasing apoptotic tendency in endothelial cells.
Reference
[1].Bernd R. Binder. A novel application for murine double minute 2 antagonists: the p53 tumor suppressor network also controls angiogenesis. Circ Res. 2007; 100: 13-14
| Kinase experiment [1]: | |
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Biacore studies |
Competition assays are performed on a Biacore S51. A Series S Sensor chip CM5 is derivatized for immobilization of a PentaHis antibody for capture of the His-tagged p53. The level of capture is ~ 200 response units. The concentration of MDM2 protein is kept constant at 300 nM. Test compounds are dissolved in DMSO at 10 mM and further diluted to make a concentration series of inhibitor in each MDM2 test sample. The assays are run at 25 °C in running buffer (10 mM Hepes, 0.15 M NaCl, 2% DMSO). MDM2-p53 binding in the presence of inhibitor is calculated as a percentage of binding in the absence of inhibitor and IC50 is calculated using Microsoft Excel. |
| Cell experiment [2]: | |
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Cell lines |
Gastric cancer cell lines with wild-type p53 (MKN-45, NUGC-4, and SUN-1 cells) |
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Preparation method |
The solubility of this compound in DMSO is >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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Reacting condition |
0.2, 1, 5, 10, and 20 μM for 3 days |
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Applications |
Nutlin-3 (10 μM, and 20 μM) suppressed the growth and induced apoptosis of gastric cancer cells with wild-type p53. |
| Animal experiment [2, 3]: | |
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Animal models |
SMMC7721/As orthotopic hepatic tumor model; Xenograft model of MKN-45 cells injected s.c. into the right flank of mice under anesthesia. |
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Dosage form |
200 mg/kg, p.o., twice a day, for 28 days; or 40 mg/kg, i.p., every 2 days for 2 weeks |
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Applications |
Nutlin-3 potentiated the antitumor effects of arsenic trioxide in an orthotopic hepatic tumor model and inhibited the metastasis to lung. Moreover, nutlin-3 (40 mg/kg) showed antitumor activity in a xenograft model of a gastric cancer cell line (MKN-45) with wild-type p53 and amplified human homolog of murine double minute 2 (MDM2). |
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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. Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., Fotouhi, N. and Liu, E. A. (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 303, 844-8482 2. Endo, S., Yamato, K., Hirai, S., Moriwaki, T., Fukuda, K., Suzuki, H., Abei, M., Nakagawa, I. and Hyodo, I. (2011) Potent in vitro and in vivo antitumor effects of MDM2 inhibitor nutlin-3 in gastric cancer cells. Cancer Sci. 102, 605-613 3. Zheng, T., Yin, D., Lu, Z., Wang, J., Li, Y., Chen, X., Liang, Y., Song, X., Qi, S., Sun, B., Xie, C., Meng, X., Pan, S., Liu, J., Jiang, H. and Liu, L. (2014) Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in Hepatocellular Carcinoma. Mol Cancer. 13, 133 |
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| Cas No. | 890090-75-2 | SDF | |
| 别名 | 4-[[4,5-双(4-氯苯基)-4,5-二氢-2-[4-甲氧基-2-(1-甲基乙氧基)苯基]-1H-咪唑-1-基]羰基]-2-哌嗪酮,Nutlin 3,MDM2 Antagonist | ||
| 化学名 | 4-[4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one | ||
| Canonical SMILES | CC(C)OC1=C(C=CC(=C1)OC)C2=NC(C(N2C(=O)N3CCNC(=O)C3)C4=CC=C(C=C4)Cl)C5=CC=C(C=C5)Cl | ||
| 分子式 | C30H30Cl2N4O4 | 分子量 | 581.5 |
| 溶解度 | ≥ 58.2 mg/mL in DMSO, ≥ 5.69 mg/mL in EtOH with ultrasonic | 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 | 1.7197 mL | 8.5985 mL | 17.1969 mL |
| 5 mM | 0.3439 mL | 1.7197 mL | 3.4394 mL |
| 10 mM | 0.172 mL | 0.8598 mL | 1.7197 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
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet