Nutlin-3 (Synonyms: Nutlin 3b) |
Katalog-Nr.GC16051
One-Click Copy Product Info
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A racemic mixture of (?)-nutlin-3 and (+)-nutlin-3
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 890090-75-2
Sample solution is provided at 25 µL, 10mM.
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Nutlin-3, a tetra-substituted imidazoline, is a potent and selective small-molecule antagonist of murine double minute 2 (MDM2), which occupies the binding site of p53 in MDM2 and consequently prevent MDM2 binding to p53 leading to the disruption of the autoregulator feedback loop and the fostering of the p53 tumor suppressor network. It also binds to murine double minute 4 (MDM4), which is another component of the p35 tumor surveillance pathway. Nutlin-3 is being investigated as an antitumor agent for its antiangiogenic activity in cells through inhibiting endothelial cell migration, inducing cell cycle arrest, and increasing apoptotic tendency in endothelial cells.
Reference
[1].Bernd R. Binder. A novel application for murine double minute 2 antagonists: the p53 tumor suppressor network also controls angiogenesis. Circ Res. 2007; 100: 13-14
| Kinase experiment [1]: | |
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Biacore studies |
Competition assays are performed on a Biacore S51. A Series S Sensor chip CM5 is derivatized for immobilization of a PentaHis antibody for capture of the His-tagged p53. The level of capture is ~ 200 response units. The concentration of MDM2 protein is kept constant at 300 nM. Test compounds are dissolved in DMSO at 10 mM and further diluted to make a concentration series of inhibitor in each MDM2 test sample. The assays are run at 25 °C in running buffer (10 mM Hepes, 0.15 M NaCl, 2% DMSO). MDM2-p53 binding in the presence of inhibitor is calculated as a percentage of binding in the absence of inhibitor and IC50 is calculated using Microsoft Excel. |
| Cell experiment [2]: | |
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Cell lines |
Gastric cancer cell lines with wild-type p53 (MKN-45, NUGC-4, and SUN-1 cells) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0.2, 1, 5, 10, and 20 μM for 3 days |
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Applications |
Nutlin-3 (10 μM, and 20 μM) suppressed the growth and induced apoptosis of gastric cancer cells with wild-type p53. |
| Animal experiment [2, 3]: | |
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Animal models |
SMMC7721/As orthotopic hepatic tumor model; Xenograft model of MKN-45 cells injected s.c. into the right flank of mice under anesthesia. |
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Dosage form |
200 mg/kg, p.o., twice a day, for 28 days; or 40 mg/kg, i.p., every 2 days for 2 weeks |
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Applications |
Nutlin-3 potentiated the antitumor effects of arsenic trioxide in an orthotopic hepatic tumor model and inhibited the metastasis to lung. Moreover, nutlin-3 (40 mg/kg) showed antitumor activity in a xenograft model of a gastric cancer cell line (MKN-45) with wild-type p53 and amplified human homolog of murine double minute 2 (MDM2). |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1. Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., Fotouhi, N. and Liu, E. A. (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 303, 844-8482 2. Endo, S., Yamato, K., Hirai, S., Moriwaki, T., Fukuda, K., Suzuki, H., Abei, M., Nakagawa, I. and Hyodo, I. (2011) Potent in vitro and in vivo antitumor effects of MDM2 inhibitor nutlin-3 in gastric cancer cells. Cancer Sci. 102, 605-613 3. Zheng, T., Yin, D., Lu, Z., Wang, J., Li, Y., Chen, X., Liang, Y., Song, X., Qi, S., Sun, B., Xie, C., Meng, X., Pan, S., Liu, J., Jiang, H. and Liu, L. (2014) Nutlin-3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in Hepatocellular Carcinoma. Mol Cancer. 13, 133 |
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| Cas No. | 890090-75-2 | SDF | |
| Überlieferungen | Nutlin 3b | ||
| Chemical Name | 4-[4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazole-1-carbonyl]piperazin-2-one | ||
| Canonical 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 | ||
| Formula | C30H30Cl2N4O4 | M.Wt | 581.5 |
| Löslichkeit | ≥ 58.2 mg/mL in DMSO, ≥ 5.69 mg/mL in EtOH with ultrasonic | 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7197 mL | 8.5985 mL | 17.1969 mL |
| 5 mM | 343.9 μL | 1.7197 mL | 3.4394 mL |
| 10 mM | 172 μL | 859.8 μL | 1.7197 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
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 saline, 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
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)