Home Apoptosis MDM2/MDMX antagonist - E3 Ligase antagonist Nutlin-3 仅限科研使用

Nutlin-3

Nutlin-3是一种有效的，选择性Mdm2(它自身和p53的环指依赖性泛素蛋白连接酶)拮抗剂，无细胞试验中IC50为90 nM；可稳定p53缺陷细胞中的p73。

Nutlin-3 Chemical Structure

Nutlin-3 Chemical Structure

CAS: 890090-75-2

规格 价格 库存 购买数量
10mM (1mL in DMSO) 1515.15 现货
5mg 900.36 现货
25mg 3026.07 现货
100mg 7939.67 现货
1g 24488.1 现货
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常与Nutlin-3一起在实验中被使用的化合物

Sorafenib

Nutlin-3和Sorafenib联合使用可增加p53(wild-type) OCI-AML3及p53(deleted) HL-60细胞的凋亡和自噬。

Zauli G, et al. Haematologica. 2012 Nov;97(11):1722-30.

Tozasertib (VX-680)

Nutlin-3和Tozasertib联合疗法选择性杀死p53受损细胞并抑制表达野生型p53的细胞增殖。

Cheok CF, et al. Cell Death Differ. 2010 Sep;17(9):1486-500.

Rucaparib

Nutlin-3和Rucaparib增强TP53卵巢癌细胞(A2780和IGROV-1细胞)的细胞死亡和G2/M细胞周期的百分比。

Zanjirband M, et al. Oncotarget. 2017 Jul 15;8(41):69779-69796.

Aspirin

Nutlin-3和Aspirin抑制HepG2细胞的增殖和凋亡，并减少体内肿瘤体积和肿瘤血管生成。

Miao R, et al. Mol Med Rep. 2018 Mar; 17(3): 3735–3743.

Nutlin-3相关产品

相关信号通路图

MDM2/MDMX Signaling Pathways

MDM2/MDMX信号通路图

细胞实验数据示例

细胞系 实验类型 给药浓度 孵育时间 活性描述 文献信息
SK-BR-7 Function Assay 10 μM 24 h inhibits TGF-β3-induced EPHB2 mRNA and protein expression 25257729
SUM102PT Function Assay 10 μM 24 h inhibits TGF-β3-induced EPHB2 mRNA and protein expression 25257729
RAW 264.7 Function Assay 10 μM 30 min prevents the p53 reduction in response to LPS 25172547
RAW 264.7 Function Assay 10 μM 30 min reduces the LPS-augmented the NF-κB luciferase reporter gene activity 25172547
RAW 264.7 Function Assay 10 μM 30 min inhibits LPS-induced NO production  25172547
MCF7  Cell Viability Assay 2.5 µM 5 d sensitizes MCF7 to PARP inhibition 25085902
MCF7  Function Assay 2.5 µM 48 h decreases the homologous DSB repair frequencies 25085902
ACHN Cell Viability Assay 0.5-10 μM 0-6 d inhibits proliferation in a dose-dependent manner 25067787
Caki-2 Cell Viability Assay 0.5-10 μM 0-6 d inhibits proliferation in a dose-dependent manner 25067787
A498 Cell Viability Assay 0.5-10 μM 0-6 d inhibits proliferation in a dose-dependent manner 25067787
115 Cell Viability Assay 0.5-10 μM 0-6 d inhibits proliferation in a dose-dependent manner 25067787
117 Cell Viability Assay 0.5-10 μM 0-6 d inhibits proliferation in a dose-dependent manner 25067787
ACHN Function Assay 0.5/1/5 μM 48 h leads to increased expression of p53 and some p53 target genes: MDM2, and p21 25067787
Caki-2 Function Assay 0.5/1/5 μM 48 h leads to increased expression of p53 and some p53 target genes: MDM2, and p21 25067787
A498 Function Assay 0.5/1/5 μM 48 h leads to increased expression of p53 and some p53 target genes: MDM2, and p21 25067787
115 Function Assay 0.5/1/5 μM 48 h leads to increased expression of p53 and some p53 target genes: MDM2, and p21 25067787
ACHN Growth Inhibition Assay 5 μM 48 h induces cell cycle arrest  25067787
Caki-2 Growth Inhibition Assay 5 μM 48 h induces cell cycle arrest  25067787
A498 Growth Inhibition Assay 5 μM 48 h induces cell cycle arrest  25067787
115 Growth Inhibition Assay 5 μM 48 h induces cell cycle arrest  25067787
ACHN Function Assay 5 μM 48 h induces p53-dependent senescence  25067787
Caki-2 Function Assay 5 μM 48 h induces p53-dependent senescence  25067787
A498 Function Assay 5 μM 48 h induces p53-dependent senescence  25067787
115 Function Assay 5 μM 48 h induces p53-dependent senescence  25067787
MOLM-13 Function Assay 6 μM 0-8 h increases the levels of p53, MDM2, p21 and acetylated p53 24885082
MOLM-13 Function Assay 6 μM 6 h enhances the acetylation of histone H2B and heat shock proteins Hsp27 and Hsp90 24885082
U2OS  Function Assay 20 μM 24 h increases the mRNA levels of BCL2A1, BCLXL andBCLW 24867259
AML2 Apoptosis Assay 2/10 μM 24/48 h induces apoptosis 24659749
MOML13 Apoptosis Assay 2/10 μM 24/48 h induces apoptosis 24659749
AML2 Function Assay 10μM 2/4 h increases the level of p53 24659749
AML3 Function Assay 10μM 2/4 h increases the level of p53 24659749
MOML13 Function Assay 10μM 2/4 h increases the level of p53 24659749
BeWo Function Assay 30 µM 24 h increases p53, Mdm2, p21 and Puma at the protein level 24498154
BeWo Apoptosis Assay 30 µM 24 h increases apoptosis 24498154
OCI Function Assay 10 μM 24 h upregulates the SOCS-1 expression 24473562
MOLM Function Assay 10 μM 24 h upregulates the SOCS-1 expression 24473562
U2OS  Function Assay 20 μM 24 h increases the levels of the HO-1 protein as well as the p53 protein 24366007
RKO Function Assay 20 μM 24 h increases the levels of the HO-1 protein as well as the p53 protein 24366007
U2OS  Function Assay 20 μM 24 h induces HO-1 expression at the level of transcription 24366007
RKO Function Assay 20 μM 24 h induces HO-1 expression at the level of transcription 24366007
SMMC-7721  Cell Viability Assay 1.25-20 μM 24/48/72 h inhibits cell proliferation dose and time dependently 24286312
HuH-7 Cell Viability Assay 1.25-20 μM 24/48/72 h inhibits cell proliferation dose and time dependently 24286312
SMMC-7721  Apoptosis Assay 20 μM 48 h induces apoptosis 24286312
HuH-7 Apoptosis Assay 20 μM 48 h induces apoptosis 24286312
SMMC-7721  Function Assay 10 μM 36 h down-regulates the protein expression level of phospho-Ser392-p53 24286312
MCF-10CA1a Function Assay 10 μM 24 h inhibits TGF-β3-induced EPHB2 mRNA and protein expression 25257729
MCF-10CA1a Function Assay 10 μM 24 h decreases the TGF-β3-induced mRNA levels ofMMP2, MMP9, and integrin β 3 25257729
MCF-10A1  Function Assay 10 μM 24/48 h inhibits migration of normal breast epithelial  25257729
MCF-10CA1a Function Assay 10 μM 48 h inhibits basal invasion and reduced TGF-β3-induced invasion to basal levels 25257729
HCT116  Function Assay 10 µM 24 h causes a p53-dependent tetraploid G1-arrest in diploid HCT116 clones D3 and D8 25380055
A2780 Function Assay 10 μM 21h  decreases the FoxM1 levels 25426548
NCI-H23 Function Assay 10 μM 21h  decreases the FoxM1 levels 25426548
A2780 Function Assay 10 μM 21h  increases p53 protein levels 25426548
NCI-H23 Function Assay 10 μM 21h  increases p53 protein levels 25426548
OVCAR10 Function Assay 10 μM 21h  increases p53 protein levels 25426548
MCF-7 Function Assay 10 μM 0-24 h induces p53 and p21/Cip1 25482373
SMMC-7721 Function Assay 10 μM 36 h causes the ectopic expression of IFI16 25544361
SMMC-7721 Function Assay 10 μM 48 h increases the expression level of IFNB1 mRNA 25544361
SMMC-7721 Function Assay 10 μM 48 h induces the chromatin-bound protein IFI16 to partially localize in the cytoplasm  25544361
SMMC-7721 Function Assay 10 μM 48 h causes DNA DSB damage 25544361
DU4475  Function Assay 5/10/20 μM 24 h downregulates Toca-1 dose dependently 25547174
C2C12 Growth Inhibition Assay 10 μM  24/48/72 h inhibits cells proliferation and differentiation 25871794
L6 Growth Inhibition Assay 10 μM  24/48/72 h inhibits cells proliferation and differentiation 25871794
C666-1 Apoptosis Assay 10 µM 48/72 h sensitizes C666-1 cells to cisplatin-induced apoptosis 26252575
C666-1  Function Assay 10 µM 24 h activates the p53 pathway, upregulating p53, p21 and Mdm2 26252575
C666-1 Cell Viability Assay 10 µM 48 h sensitizes C666-1 cells to the cytotoxic effect of cisplatin 26252575
MCF7 Growth Inhibition Assay 5 μM 48 h blocks 27-OHC-induced cell proliferation comparable to that of basal levels 26350565
HuH-7 Function Assay 10 μM 36 h down-regulates the protein expression level of phospho-Ser392-p53 24286312
A2780 Function Assay 5/10/20 μM 24 h upregulates p53, MDM2, p21 and DR5 protein levels dose dependently  24136147
H460 Function Assay 5/10/20 μM 24 h upregulates p53, MDM2, p21 and DR5 protein levels dose dependently  24136147
Lovo  Function Assay 5/10/20 μM 24 h upregulates p53, MDM2, p21 and DR5 protein levels dose dependently  24136147
A2780 Apoptosis Assay 5/10/20 μM 24 h enhances apoptosis induction by D269H/E195R over rhTRAIL 24136147
H460 Apoptosis Assay 5/10/20 μM 24 h enhances apoptosis induction by D269H/E195R over rhTRAIL 24136147
Lovo  Apoptosis Assay 5/10/20 μM 24 h enhances apoptosis induction by D269H/E195R over rhTRAIL 24136147
MCF-7  Function Assay 10 μM inhibits cyclin D1 and Dicer  25702703
AT2 Function Assay 5/10 μM leads to a substantial accumulation of the p53 protein as well as the expression of its direct targets p21, MDM2 and the pro-apoptotic BAX and PUMA proteins  24240203
REH Function Assay 5/10 μM leads to a substantial accumulation of the p53 protein as well as the expression of its direct targets p21, MDM2 and the pro-apoptotic BAX and PUMA proteins  24240203
UoCB6 Function Assay 5/10 μM leads to a substantial accumulation of the p53 protein as well as the expression of its direct targets p21, MDM2 and the pro-apoptotic BAX and PUMA proteins  24240203
AT2 Cell Viability Assay 0-25 μM inhibits cell viability dose dependently 24240203
REH Cell Viability Assay 0-25 μM inhibits cell viability dose dependently 24240203
UoCB6 Cell Viability Assay 0-25 μM inhibits cell viability dose dependently 24240203
HepG2 Growth Inhibition Assay 72 h IC50=35.86 ± 2.9 μM 24884809
HepG2/As Growth Inhibition Assay 72 h IC50=68.13 ± 9.6 μM 24884809
SMMC7721 Growth Inhibition Assay 72 h IC50=31.28 ± 4.2 μM 24884809
SMMC7721/Ac Growth Inhibition Assay 72 h IC50=55.21 ± 5.03 μM 24884809
Huh-7 Growth Inhibition Assay 72 h IC50=33.96 ± 3.9 μM 24884809
Hep3B Growth Inhibition Assay 72 h IC50=20.18 ± 1.84 μM 24884809
CRL-5908 Growth Inhibition Assay 24 h IC50=38.71 ± 2.43 μM 26125230
A549-920 Growth Inhibition Assay 24 h IC50=33.85 ± 4.84 μM 26125230
A549-NTC Growth Inhibition Assay 24 h IC50=19.42 ± 1.96 μM 26125230
A549 Growth Inhibition Assay 24 h IC50=17.68 ± 4.52 μM 26125230
U87MG Function assay 10 mins Binding affinity to MDM2 in human U87MG cells assessed as inhibition of MDM2/p53 protein interaction after 10 mins by quantitative sandwich immuno assay, IC50 = 0.1045 μM. 27050782
U87MG Antiproliferative assay 48 hrs Antiproliferative activity against human U87MG cells expressing wild type p53 after 48 hrs by MTS assay, IC50 = 6.5 μM. 27050782
U343MG Antiproliferative assay 48 hrs Antiproliferative activity against human U343MG cells expressing wild type p53 after 48 hrs by MTS assay, IC50 = 12.6 μM. 27050782
SW620 Cytotoxicity assay 72 hrs Cytotoxicity against human SW620 cells after 72 hrs by SRB assay, IC50 = 0.38 μM. ChEMBL
A549 Cytotoxicity assay 72 hrs Cytotoxicity against human A549 cells after 72 hrs by SRB assay, IC50 = 0.41 μM. ChEMBL
SJSA1 Cytotoxicity assay 72 hrs Cytotoxicity against human SJSA1 cells after 72 hrs by SRB assay, IC50 = 1.81 μM. ChEMBL
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT116 cells after 72 hrs by SRB assay, IC50 = 4.63 μM. ChEMBL
PC3 Cytotoxicity assay 72 hrs Cytotoxicity against human PC3 cells after 72 hrs by SRB assay, IC50 = 6.37 μM. ChEMBL
HepG2 Apoptosis Assay induces apoptosis 24884809
SMMC7721 Apoptosis Assay induces apoptosis 24884809
Huh-7 Apoptosis Assay induces apoptosis 24884809
Hep3B Apoptosis Assay induces apoptosis 24884809
C666-1 Growth Inhibition Assay IC50=19.95±8.93 μM 26252575
NP460 Growth Inhibition Assay IC50=22.85±1.18 μM 26252575
NP69 Growth Inhibition Assay IC50=31.69±2.54 μM 26252575
点击查看更多细胞系数据

生物活性

产品描述 Nutlin-3是一种有效的，选择性Mdm2(它自身和p53的环指依赖性泛素蛋白连接酶)拮抗剂，无细胞试验中IC50为90 nM；可稳定p53缺陷细胞中的p73。
靶点
MDM2 [5]
(Cell-free assay)
180 nM
体外研究(In Vitro)
体外研究活性

Nutlin-3有效抑制MDM2-p53相互作用，IC50 为 90 nM, 导致p53通路激活。Nutlin-3 处理含野生型p53的细胞，如HCT116, RKO 和SJSA-1,诱导MDM2 和p21表达, 且具有有效的抗增殖活性，IC50 为~1.5 μM, 但是作用于含突变型p53的细胞系 SW480和 MDA-MB-435没有效果。10 μM Nutlin-3处理 SJSA-1细胞48小时，显著诱导caspase依赖的细胞凋亡，凋亡达~45%。虽然Nutlin-3也抑制人皮肤 (1043SK) 和小鼠胚胎 (NIH/3T3) 的生长和活力，IC50分别为2.2 μM 和1.3 μM, 10 μM Nutlin-3处理一周后仍保留细胞活力，而3 μM Nutlin-3 处理SJSA-1细胞后，细胞则无活力。[1] Nutlin-3 不诱导p53在关键丝氨酸残基的磷酸化，在特定DNA结合序列没有区别，且与基因毒性药物Doxorubicin诱导的磷酸化p53相比， 使p53靶点基因转活，说明 p53 在关键丝氨酸残基的磷酸化对转录激活和凋亡是非必需的。[2] 虽然与MDM2相比，Nutlin-3 与MDMX 结合的效率低一点, Nutlin-3作用于视网膜母细胞瘤细胞(Weri1)，能抑制MDMX–p53相互作用，且诱导 p53通路，IC50为0.7 μM。[3] 30 μM Nutlin-3作用于无野生型p53的细胞，也扰乱内源性p73-HDM2 相互作用，且增强p73稳定性和促凋亡活性, 导致细胞生长受抑制，和诱导凋亡。[4]
激酶实验 Biacore 研究
在Biacore S51上进行竞争性实验。衍生一系列S传感器芯片CM5，用于固定 PentaHis抗体，为了捕获 His-标记的p53。捕获的水平为~200反应单位(1 反应单位对应于1 pg 蛋白/ mm2)。MDM2蛋白浓度一直维持在300 nM。Nutlin-3 溶于DMSO，浓度为10 mM，然后进一步稀释，在每个MDM2实验样本中产生系列浓度的Nutlin-3。在电泳缓冲液(10 mM Hepes,0.15 M NaCl, 2% DMSO)中25oC下进行实验。在Nutlin-3存在时，计算MDM2-p53结合情况，作为结合百分数， 使用Microsoft Excel计算IC50。
细胞实验 细胞系 HCT116, RKO, SJSA-1, SW480, 和 MDA-MB-435
浓度 溶于DMSO,终浓度为~ 30 μM
孵育时间 8, 24, 和 48 小时
方法

使用不同浓度Nutlin-3处理细胞8, 24和 48 小时。通过实时PCR分析p21 和MDM2基因转录水平,通过Western Blotting分析蛋白水平。通过MTT实验测定细胞活力。 通过末端脱氧核苷酸转移酶调节的脱氧尿苷三磷酸缺口末端标记法（TUNEL）染色，使用流式细胞仪和荧光显微镜测定细胞凋亡。
实验图片 检测方法 检测指标 实验图片 PMID
Western blot MDM2 / p53 / ALKBH2 / p21 / PUMA RRM1 / RRM2 / p53R2 / p21 / p53 / pS6 / S6 23258843
Immunofluorescence Lamin A / Lamin C / p16 / H3K9me3 Merlin / cyclin D1 / p53 / MDM2 p53 30728349
Growth inhibition assay Cell viability 29286113
体内研究(In Vivo)
体内研究活性

Nutlin-3 按200 mg/kg 剂量口服处理，每天两次，持续3周，显著抑制SJAS-1移植瘤生长，抑制达90%, 而Doxorubicin抑制81%肿瘤生长。[1]
动物实验 Animal Models 皮下注射 SJSA-1细胞的雌性无胸腺Nu/Nu-nuBR裸鼠
Dosages 200 mg/kg
Administration 口服处理，每天两次

化学信息&溶解度

分子量 581.5 分子式

C30H30Cl2N4O4
CAS号 890090-75-2 SDF Download Nutlin-3 SDF
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
储存条件(自收到货起)

体外溶解度
批次：

DMSO : 100 mg/mL ( (171.96 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Ethanol : 100 mg/mL (171.96 mM)

Water : Insoluble

摩尔浓度计算器

体内溶解度
批次：

现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂

 动物体内配方计算器

实验计算

摩尔浓度计算器

质量 浓度 体积 分子量

动物体内配方计算器（澄清溶液）

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）

mg/kg g μL 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Selleck为您提供正确的澄清溶液配方）

% DMSO % % Tween 80 % ddH2O
%DMSO %

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，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；

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 ddH2O，混匀澄清。

体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。

注意：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。

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常见问题及建议解决方法

问题 1:
Is this a racemic mixture of Nutlin-3a and Nutlin-3b or just the Nutlin-3a enantiomer?

回答：
It is a racemate.

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