(±)-Nutlin-3
(Synonyms: REL-4-[[(4R,5S)-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) 目录号 : GC14154
A racemic mixture of (?)-nutlin-3 and (+)-nutlin-3
Cas No.:548472-68-0
Sample solution is provided at 25 µL, 10mM.
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(±)-Nutlin-3 is a potent and selective MDM2 antagonist with IC50 value of 0.09 μM [1].
Mouse double minute 2 homolog (MDM2) is an important negative regulator of p53, a tumor suppressor. Disruption of the p53-MDM2 interaction can lead to the activation of p53 and tumor growth inhibition [1].
(±)-Nutlin-3 is a potent and selective MDM2 antagonist. In both normal and leukemic B cells, Nutlin-3 induced accumulation of p53 protein in a dose-dependent way. In B-CLL cells, Nutlin-3 also induced cell death with IC50 value of 10.4 μM and induced the transcription of p53 target genes, such as PCNA, CDKN1A/p21, GDF15, TNFRSF10B/TRAIL-R2, TP53I3/PIG3, GADD45, and DDB1 [2].
In mice bearing subcutaneous human cancer xenografts (SJSA-1), Nutlin-3 (200 mg/kg) orally treated twice a day for 20 days inhibited tumor growth by 90% [1]. In mice with established UKF-NB-3rDOX20 xenografts, Nutlin-3 (200 mg/kg) increased caspase-3 activity and induced apoptosis [3].
References:
[1].Shinohara T, Uesugi M. In-vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Tanpakushitsu Kakusan Koso. 2007 Oct;52(13 Suppl):1816-7.
[2].Secchiero P, Barbarotto E, Tiribelli M, et al. Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2006 May 15;107(10):4122-9.
[3].Van Maerken T, Ferdinande L, Taildeman J, et al. Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53. J Natl Cancer Inst. 2009 Nov 18;101(22):1562-74.
Cell experiment: | Human non-small-cell lung carcinoma wild type p53-containing H460 and A549, human non-small-cell lung carcinoma p53-null H1299, and human colon cancer HCT116 (p53+/+ and p53-/-) cells are used. Cells (1.5×105) are plated into 6-well plates, and incubated at 37°C overnight. After treatment of Inauhzin and Nutlin 3 at the indicated concentrations for 48 h, cells are harvested, fixed in 70% ice-cold ethanol overnight at -20°C, resuspended in propidium iodide-solution (50 µg/mL PI, 0.1 mg/mL RNase A, 0.05% Tritin X-100 in PBS) for 40 min at 37°C, then analyzed for DNA content using a flow cytometer and proprietary software[2]. |
Animal experiment: | Mice[2] Five-week-old female SCID mice are used. Mice are subcutaneously inoculated with 3×106 HCT116p53+/+ cells in the right flank and tumor growth is monitored with calipers. After the mean tumor volume reaches 50-100 mm3, animals are administered Inauhzin intraperitoneally (IP), Nutlin 3 orally, or vehicles (4% DMSO for Inauhzin, EtOH: Tween: 5% Glucose=5:5:90 for Nutlin 3). Tumor volume is measured every other day, and inhibition of tumor growth (T/C) is calculated on the last day of treatment. |
References: [1]. Yu Z, et al. Design, synthesis and biological evaluation of sulfamide and triazole benzodiazepines as novel p53-MDM2 inhibitors. Int J Mol Sci. 2014 Sep 5;15(9):15741-53. | |
| Cas No. | 548472-68-0 | SDF | |
| 别名 | REL-4-[[(4R,5S)-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 | ||
| 化学名 | 4-(4,5-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one | ||
| Canonical SMILES | ClC1=CC=C(C=C1)C2N(C(N(C3)CCNC3=O)=O)C(C(C=CC(OC)=C4)=C4OC(C)C)=NC2C(C=C5)=CC=C5Cl | ||
| 分子式 | C30H30Cl2N4O4 | 分子量 | 581.49 |
| 溶解度 | DMSO : ≥ 50 mg/mL (85.99 mM) Water : < 0.1 mg/mL (insoluble) | 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 | 8.5986 mL | 17.1972 mL |
| 5 mM | 0.3439 mL | 1.7197 mL | 3.4394 mL |
| 10 mM | 0.172 mL | 0.8599 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: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet