AMG232
(Synonyms: 2-((3R,5R,6S)-5-(3-氯苯基)-6-(4-氯苯基)-1-((S)-1-(异丙基磺酰基)-3-甲基丁烷-2-基)-3-甲基-2-氧代哌啶-3-基)乙酸,AMG 232;AMG-232) 目录号 : GC15828
An inhibitor of the MDM2 and p53 interaction
Cas No.:1352066-68-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1,2]: | |
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Cell lines |
SJSA-1, HCT116, and ACHN tumor cell lines |
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Preparation method |
Soluble in DMSO. 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 |
0.1, 1, or 10 μmol/L, 24 hours |
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Applications |
AMG 232 induced p53 signaling with an IC50 of 0.6 ± 0.4 nmol/L. AMG 232 inhibits cell proliferation in p53 WT cell lines. AMG 232 treatment inhibited the growth of cells with IC50 values ranging from 0.1 to 1 μmol/L. AMG 232 caused a dose-dependent accumulation of p53 and increased p21, MDM2, and PUMA proteins in both MDM2-amplified SJSA-1 cells and non–MDM2-amplified HCT116 cells. AMG 232 potently inhibited proliferation of non-MDM2-amplified HCT116 colorectal cells. |
| Animal experiment [1,2]: | |
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Animal models |
Female athymic nude mice bearing SJSA-1 cells and HCT116 cells |
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Dosage form |
10 mg/kg, 25 mg/kg, 75 mg/kg; once per day by oral gavage, |
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Application |
AMG 232 (10 mg/kg, 25 mg/kg, 75 mg/kg, 6 hours) treatment resulted in time- and dose-dependent induction of p21 mRNA in SJSA-1 tumor. AMG 232 treatment also caused a dose-dependent induction of p21, MDM2, and PUMA mRNA in HCT116 tumors. AMG 232 (100 mg/kg, 4 days) treatment caused cell-cycle arrest and induced apoptosis in mice bearing SJSA-1 or HCT116 tumors. AMG 232 (orally once daily) enhanced the antitumor activity of DNA-damaging cytotoxics. AMG 232 displayed robust tumor growth inhibition with an ED50 of 9.1 mg/kg q.d. AMG 232 caused a dose-dependent tumor growth inhibition with an ED50 of 16 mg/kg. |
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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]. Canon J, Osgood T, Olson S H, et al. The MDM2 inhibitor AMG 232 demonstrates robust anti-tumor efficacy and potentiates the activity of p53-inducing cytotoxic agents[J]. Molecular cancer therapeutics, 2015: molcanther. 0710.2014. [2]. Rew Y, Sun D. Discovery of a small molecule MDM2 inhibitor (AMG 232) for treating cancer[J]. 2014. |
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AMG-232 is a novel inhibitor of p53-MDM2 with IC50 value of 9.2 nM [1].
Tumor protein p53 (p53) is a very unstable protein with a half-life ranging from 5 to 30 min and participates in a variety of anticancer processes, such as inducing cell apoptosis and inhibiting angiogenesis. Mouse double minute 2 homolog (MDM2), also named as E3 ubiquitin-protein ligase Mdm2, involves in mediating p53 tumor suppressor. It has been conclusively demonstrated p53 is under-expressed in tumor cells [2].
AMG-232 is a potent p53-MDM2 interaction inhibitor and is regarded as a promising drug in clinic. When tested with SJSA-1 tumor cell line, AMG-232 treatment resulted in cell-cycle arrest and inhibition of tumor cell proliferation via binding to MDM2 protein and robustly inducing p53 activity. It was shown that p53-MDM2 bond rang from a Kd of 60 to 700 nM Depending on the length of p53 peptide [3].
In mouse model with SJSA-1 tumor cells subcutaneous xenograft, co-administration of AMG-232 and chemotherapies induced DNA damage and p53 activity which resulted in significantly superior antitumor efficacy and regression through arresting cell growth and inducting apoptosis [3].
References:
[1]. Rew, Y., et al., Discovery of AM-7209, a potent and selective 4-amidobenzoic acid inhibitor of the MDM2-p53 interaction. J Med Chem, 2014. 57(24): p. 10499-511.
[2]. Moll, U.M. and O. Petrenko, The MDM2-p53 interaction. Mol Cancer Res, 2003. 1(14): p. 1001-8.
[3]. Canon, J., et al., The MDM2 Inhibitor AMG 232 Demonstrates Robust Antitumor Efficacy and Potentiates the Activity of p53-Inducing Cytotoxic Agents. Mol Cancer Ther, 2015. 14(3): p. 649-58.
| Cas No. | 1352066-68-2 | SDF | |
| 别名 | 2-((3R,5R,6S)-5-(3-氯苯基)-6-(4-氯苯基)-1-((S)-1-(异丙基磺酰基)-3-甲基丁烷-2-基)-3-甲基-2-氧代哌啶-3-基)乙酸,AMG 232;AMG-232 | ||
| 化学名 | 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid | ||
| Canonical SMILES | CC(S(C[C@@H](N([C@H](C1=CC=C(Cl)C=C1)[C@@H](C2=CC=CC(Cl)=C2)C[C@]3(C)CC(O)=O)C3=O)C(C)C)(=O)=O)C | ||
| 分子式 | C28H35Cl2NO5S | 分子量 | 568.55 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 mg/ml,Ethanol:PBS (pH 7.2)(1:2): 0.33 mg/ml | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
| 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 | 1.7589 mL | 8.7943 mL | 17.5886 mL |
| 5 mM | 0.3518 mL | 1.7589 mL | 3.5177 mL |
| 10 mM | 0.1759 mL | 0.8794 mL | 1.7589 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。