(±)-Nutlin-3 (Synonyms: Nutlin 3b) |
| Catalog No.GC14154 |
MDM2 antagonist, potent and selective
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 548472-68-0
Sample solution is provided at 25 µL, 10mM.
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(±)-Nutlin-3 is a potent and selective MDM2 antagonist with IC50 value of 0.09 μM [1].
Mouse double minute 2 homolog (MDM2) is an important negative regulator of p53, a tumor suppressor. Disruption of the p53-MDM2 interaction can lead to the activation of p53 and tumor growth inhibition [1].
(±)-Nutlin-3 is a potent and selective MDM2 antagonist. In both normal and leukemic B cells, Nutlin-3 induced accumulation of p53 protein in a dose-dependent way. In B-CLL cells, Nutlin-3 also induced cell death with IC50 value of 10.4 μM and induced the transcription of p53 target genes, such as PCNA, CDKN1A/p21, GDF15, TNFRSF10B/TRAIL-R2, TP53I3/PIG3, GADD45, and DDB1 [2].
In mice bearing subcutaneous human cancer xenografts (SJSA-1), Nutlin-3 (200 mg/kg) orally treated twice a day for 20 days inhibited tumor growth by 90% [1]. In mice with established UKF-NB-3rDOX20 xenografts, Nutlin-3 (200 mg/kg) increased caspase-3 activity and induced apoptosis [3].
References:
[1].Shinohara T, Uesugi M. In-vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Tanpakushitsu Kakusan Koso. 2007 Oct;52(13 Suppl):1816-7.
[2].Secchiero P, Barbarotto E, Tiribelli M, et al. Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2006 May 15;107(10):4122-9.
[3].Van Maerken T, Ferdinande L, Taildeman J, et al. Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53. J Natl Cancer Inst. 2009 Nov 18;101(22):1562-74.
Cell experiment: | 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]. |
Animal experiment: | 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. |
References: [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. | |
| Cas No. | 548472-68-0 | SDF | |
| Synonyms | Nutlin 3b | ||
| Chemical Name | 4-(4,5-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one | ||
| Canonical SMILES | ClC1=CC=C(C=C1)C2N(C(N(C3)CCNC3=O)=O)C(C(C=CC(OC)=C4)=C4OC(C)C)=NC2C(C=C5)=CC=C5Cl | ||
| Formula | C30H30Cl2N4O4 | M.Wt | 581.49 |
| Solubility | DMSO : ≥ 50 mg/mL (85.99 mM) Water : < 0.1 mg/mL (insoluble) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.7197 mL | 8.5986 mL | 17.1972 mL |
| 5 mM | 0.3439 mL | 1.7197 mL | 3.4394 mL |
| 10 mM | 0.172 mL | 0.8599 mL | 1.7197 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 32 reference(s) in Google Scholar.)
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