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
CAS: 890090-75-2
产品质控
批次：
纯度：
99.59%
99.59
常与Nutlin-3一起在实验中被使用的化合物
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。
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.
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.
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。
Nutlin-3相关产品
| 相关靶点 | MDM2 MDMX p53-MDM2 interaction | 点击展开 |
|---|---|---|
| 相关产品 | Nutlin-3a RG-7112 Idasanutlin (RG7388) SAR405838 NSC 207895 NVP-CGM097 Siremadlin (HDM201) Nutlin-3b MX69 YH239-EE | 点击展开 |
| 相关化合物库 | 自噬化合物库 凋亡分子化合物库 铁死亡化合物库 细胞焦亡化合物库 线粒体靶向化合物库 | 点击展开 |
相关信号通路图
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。 | ||
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| 靶点 |
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| 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] |
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| 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。 |
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| 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 |
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23258843 | |
| Immunofluorescence | Lamin A / Lamin C / p16 / H3K9me3 Merlin / cyclin D1 / p53 / MDM2 p53 |
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30728349 | |
| Growth inhibition assay | Cell viability |
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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] |
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|---|---|---|
| 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) | |||
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体外溶解度 |
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 |
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体内溶解配方 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
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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