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Nutlin-3MDM2 antagonist,inhibits MDM2-p53 interaction


Catalog No. A4228
Size Price Stock Qty
10mM (in 1mL DMSO) $150.00 In stock
Evaluation Sample $28.00 In stock
5mg $80.00 In stock
10mg $120.00 In stock
25mg $260.00 In stock
100mg $590.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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Chemical structure


Related Biological Data


Related Biological Data


Related Biological Data


Biological Activity

Description Nutlin-3 is a potent and selective antagonist of Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) with IC50 of 90 nM.
Targets Mdm2          
IC50 90 nM          


Kinase experiment [1]:

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]:

Cell lines

Gastric cancer cell lines with wild-type p53 (MKN-45, NUGC-4, and SUN-1 cells)

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.

Reacting condition

0.2, 1, 5, 10, and 20 μM for 3 days


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]:

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.

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


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).

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.


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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Chemical Properties

Cas No. 890090-75-2 SDF Download SDF
Synonyms Nutlin 3,MDM2 Antagonist
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
Solubility >58.2mg/mL in DMSO Storage Store at -20°C
General tips N/A
Shipping Condition N/A


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. 


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