| CAS |
No.548472-68-0 |
| 英文名称 |
Nutlin3 |
| 分子式 |
C30H30Cl2N4O4 |
| 分子量 |
581.49 |
| 溶解性 |
Soluble in DMSO ≥5mg/mL |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 运输条件 |
冷藏运输 |
| MDL |
MFCD07784509 |
| 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 |
| InChIKey |
BDUHCSBCVGXTJM-UHFFFAOYSA-N |
| InChI |
InChI=1S/C30H30Cl2N4O4/c1-18(2)40-25-16-23(39-3)12-13-24(25)29-34-27(19-4-8-21(31)9-5-19)28(20-6-10-22(32)11-7-20)36(29)30(38)35-15-14-33-26(37)17-35/h4-13，16，18，27-28H，14-15，17H2，1-3H3，(H，33，37) |
| PubChem CID |
216345 |
| 靶点 |
MDM-2 |
| 通路 |
Apoptosis |
| 背景说明 |
是一种 MDM2 拮抗剂，抑制 MDM2-p53 相互作用 。 |
| 生物活性 |
Nutlin-3 is a commercial available p53-MDM2 inhibitor， with Ki of 90 nM.[1-3] |
| IC50 |
Ki: 90 nM (p53-MDM2)[1] |
| In Vitro |
Nutlin-3 is an inhibitor of the MDM2-p53 interaction. In particular， co-treatment of p53-positive HCT116 cells with 1 μM of Inauhzin and 2 μM of Nutlin-3 more significantly activated p53 as measured by its protein level as well as the level of its target p21， PUMA or cleaved PARP as indication of apoptosis[2]. Nutlin-3 is a small-molecule inhibitor that acts to inhibit MDM2 binding to p53 and subsequent p53-dependent DNA damage signaling. As a single agent， Nutlin-3 (2-10 μM) stabilizes p53 and p21WAF levels and is toxic to WTp53-22RV1 cells (IC50， 4.3 μM) but has minimal toxicity toward p53-deficient cells (IC50， >10 μM). Nutlin-3 induces p53 and p21WAF expression in a dose-dependent manner in 22RV1 cells. Short-term cell cycle assays show that， at a dose of 10 μM， Nutlin-3 increasea slightly the G1-phase fraction and decreasea S-phase fraction of all three cell lines[3]. |
| In Vivo |
Nutlin-3 can suppress the growth of xenograft tumors derived from human osteosarcoma or leukemia cells， the anti-tumor activity of Nutlin-3 even at the dose of 200 mg/kg per oral administration is marginal in an HCT116-derived xenograft tumor model[2]. Nutlin-3 may be a useful adjunct to improve the therapeutic ratio using precision radiotherapy targeted to hypoxic cells and warrants further study in vivo[3]. |
| 细胞实验 |
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]. |
| 动物实验 |
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. |
| 数据来源文献 |
[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.
[2]. Zhang Y， et al. Inauhzin and Nutlin3 synergistically activate p53 and suppress tumor growth.Cancer Biol Ther. Cancer Biol Ther. 2012 Aug;13(10):915-24.
[3]. Supiot S， et al. Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53. Mol Cancer Ther. 2008 Apr;7(4):993-9. |
| 规格 |
1mg 5mg 10mg 25mg 50mg 100mg |
| 单位 |
瓶 |
中文
英语
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