Nutlin-3a chiral
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Nutlin-3是mouse double minute 2(MDM2)的小分子抑制剂,IC50值为0.09 μM[1]。
Nutlin-3与MDM2的TP53结合口袋结合,从而干扰MDM2介导的TP53降解。据报道,在实体瘤和淋巴瘤中,Nutlin-3引起细胞周期停滞、生长抑制和细胞凋亡。在套细胞淋巴瘤(MCL)中,Nutlin-3可以抑制wt-TP53和mt-TP53细胞的生长,诱导细胞凋亡,IC50值分别为1-10 μM和22.5 μM[2]。
在胃癌细胞系中,Nutlin-3也可以影响细胞周期,诱导MKN-45和SNU-1细胞系的G1期停滞。在几个胃癌细胞系中,Nutlin-3可以增强常规化疗剂的抗肿瘤效应。在体内实验中,Nutlin-3显著抑制异种移植肿瘤的生长[3]。
参考文献:
[1] Lyubomir T. Vassilev et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.Science.2004, 303: 844-848.
[2] Yoko Tabe, Denise Sebasigari, Linhua Jin, et al. MDM2 Antagonist Nutlin-3 Displays Antiproliferative andProapoptotic Activity in Mantle Cell Lymphoma. Clin Cancer Res. 2009, 15:933-942.
[3] Shinji Endo,Kenji Yamato,Sachiko Hirai,Toshikazu Moriwaki,Kuniaki Fukuda,Hideo Suzuki,Masato Abei,Ichiro Nakagawa and IchinosukeHyodo. Potent in vitro and in vivo antitumor effects ofMDM2 inhibitor nutlin-3 in gastric cancer cells.Cancer Science. 2011, 102 (3): 605-613.
- 1. Cesar Mendoza-Martinez, Michail Papadourakis, et al. "Energetics of a protein disorder–order transition in small molecule recognition." Chem Sci. 2022 Apr 4;13(18):5220-5229. PMID: 35655546
- 2. Xinzhi Yang, Jiangang Liu, et al. "miR-18a promotes glioblastoma development by down-regulating ALOXE3-mediated ferroptotic and anti-migration activities." Oncogenesis. 2021 Feb 12;10(2):15. PMID: 33579899
- 3. Roscoe I, Parker M, et al. "Human Serum Albumin and the p53-Derived Peptide Fusion Protein Promotes Cytotoxicity Irrespective of p53 Status in Cancer Cells." Mol Pharm. 2018 Oct 10. PMID: 30226785
- 4. Chen R, Zhou J, et al. "A Fusion Protein of the p53 Transaction Domain and the p53-Binding Domain of the Oncoprotein MdmX as an Efficient System for High-Throughput Screening of MdmX Inhibitors." Biochemistry. 2017 Jun 27;56(25):3273-3282. PMID: 28581721
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 581.49 |
Cas No. | 675576-98-4 |
Formula | C30H30Cl2N4O4 |
Synonyms | Nutlin-3a;Nutlin 3a |
Solubility | ≥29.07 mg/mL in DMSO; insoluble in H2O; ≥104.4 mg/mL in EtOH |
Chemical Name | 4-[(4S,5R)-4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one |
SDF | Download SDF |
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 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
激酶实验 [1]: | |
Biacore研究 |
在Biacore S51上进行竞争分析。使用固定PentaHis抗体的Series S Sensor chip CM5捕获His标记的p53。捕获水平约为200个响应单元(1个响应单元相当于每平方毫米21 pg蛋白质)。MDM2蛋白浓度维持在300 nM。将Nutlin-3a溶于DMSO至浓度为10 mM,并进一步稀释Nutlin-3a,从而获得一系列的浓度。在25°C下,使用电泳缓冲液 (10 mM Hepes, 0.15 M NaCl, 2% DMSO) 进行测试。在含或不含Nutlin-3a的情况下,计算MDM2-p53结合。结果以百分比表示。使用Microsoft Excel计算IC50值。 |
激酶实验 [1]: | |
细胞系 |
HCT116和SW480细胞 |
制备方法 |
在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
反应条件 |
1、2、4、8和16 μM;8小时 |
实验结果 |
在HCT116细胞中,Nutlin-3a增加p53、MDM2和p21Waf1/Cip1的细胞水平。然而,在SW480细胞中,经过相同条件处理的细胞显示出较高的p53基础水平,而没有可检测的MDM2或p21。 |
动物实验 [1]: | |
动物模型 |
皮下人肿瘤异种移植 (SJSA-1) 裸鼠 |
给药剂量 |
200 mg/kg;口服给药;每日2次,持续20日 |
实验结果 |
Nutlin-3a抑制90%肿瘤生长。治疗结束后的尸检结果表明,小鼠体重无显著减轻,小鼠也无出现任何严重畸形。 |
其它注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。 |
References: [1]. Vassilev LT, Vu BT, Graves B, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science, 2004, 303(5659): 844-848. |
描述 | Nutlin-3是mouse double minute 2(MDM2)的小分子抑制剂,IC50值为0.09 μM。 | |||||
靶点 | MDM2 | |||||
IC50 | 0.09 μM |
质量控制和MSDS
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