Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Nutlin-3 is an MDM2 antagonist.Nutlin-3 inhibits the MDM2-p53 interaction (IC50: 0.09 μM) and activates p53. Antiproliferative agent; chemotherapeutic agent; induces apoptosis in Y cells.
Pack Size | Availability | Price/USD | Quantity |
---|---|---|---|
2 mg | In stock | $ 54.00 | |
5 mg | In stock | $ 81.00 | |
10 mg | In stock | $ 126.00 | |
25 mg | In stock | $ 261.00 | |
50 mg | In stock | $ 481.00 | |
100 mg | In stock | $ 522.00 | |
1 mL * 10 mM (in DMSO) | In stock | $ 111.00 |
Description | Nutlin-3 is an MDM2 antagonist.Nutlin-3 inhibits the MDM2-p53 interaction (IC50: 0.09 μM) and activates p53. Antiproliferative agent; chemotherapeutic agent; induces apoptosis in Y cells. |
Targets&IC50 | MDM2-p53:0.09 μM |
In vitro | Nutlin-3 acts as an inhibitor of the MDM2-p53 interaction, enhancing the activation of p53 in p53-positive HCT116 cells when used alongside 1 μM of Inauhzin and 2 μM of Nutlin-3. This results in greater elevation of p53 protein levels and its targets such as p21, PUMA, and cleaved PARP, indicating an increase in apoptosis. It functions by blocking MDM2's binding to p53, thus preventing p53-dependent DNA damage responses. At concentrations ranging from 2-10 μM, Nutlin-3 increases p53 and p21WAF levels, demonstrating toxicity to WTp53-22RV1 cells (with an IC50 of 4.3 μM) while showing minimal effects on p53-deficient cells (IC50 >10 μM). It also induces p53 and p21WAF expression in 22RV1 cells in a dose-dependent manner and can modify the cell cycle distribution by slightly increasing the G1-phase and decreasing the S-phase fractions at a 10 μM dose in three cell lines. |
In vivo | Nutlin-3 demonstrates the capability to inhibit the proliferation of xenograft tumors originating from human osteosarcoma or leukemia cells. However, its anti-tumor efficacy, even at an administered dose of 200 mg/kg orally, is minimal in models of xenograft tumors derived from HCT116. Nutlin-3 holds potential as a beneficial supplement to enhance the therapeutic effectiveness of precision radiotherapy aimed at hypoxic cells, meriting additional in vivo investigation. |
Kinase Assay | Biacore study: Competition assay is performed on a Biacore S51. A Series S Sensor chip CM5 is utilized for the immobilization of a PentaHis antibody for capture of the His-tagged p53. The level of capture is ~200 response units (1 response unit corresponds to 1 pg of protein per mm 2). The concentration of MDM2 protein is kept constant at 300 nM. Nutlin-3 is dissolved in DMSO at 10 mM and further diluted to make a concentration series of Nutlin-3 in each MDM2 test sample. The assay is run at 25°C in running buffer (10 mM Hepes, 0.15 M NaCl, 2% DMSO). MDM2-p53 binding in the presence of Nutlin-3 is calculated as a percentage of binding in the absence of Nutlin-3 and IC50 is calculated |
Cell Research | Nutlin-3 (NUT) is dissolved with DMSO (100 mM) and diluted with appropriate media[2]. 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]. |
Synonyms | Nutlin3 |
Molecular Weight | 581.49 |
Formula | C30H30Cl2N4O4 |
CAS No. | 548472-68-0 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 55 mg/mL (94.58 mM)
You can also refer to dose conversion for different animals. More
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Nutlin-3 548472-68-0 Ubiquitination E1/E2/E3 Enzyme E3 ligating enzyme E2 conjugating enzyme E1 activating enzyme Ubiquitin conjugating enzyme inhibit MDM-2/p53 Nutlin 3 Ubiquitin activating enzyme Inhibitor Nutlin3 Ubiquitin ligase inhibitor