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Nutlin-3a chiral
MDM2 inhibitor, antiproliferative and antiproapoptotic

Nutlin-3a chiral

Catalog No. A3671
Size Price Stock Qty
10mM (in 1mL DMSO) $185.00 In stock
10mg $120.00 In stock
50mg $580.00 In stock
200mg $1,980.00 In stock

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Sample solution is provided at 25 µL, 10mM.

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Chemical structure

Nutlin-3a chiral

Related Biological Data

Nutlin-3a chiral

Related Biological Data

Nutlin-3a chiral

Biological Activity

Description Nutlin-3 is a small-molecule inhibitor of mouse double minute 2 (MDM2) with IC50 value of 0.09 μM.
Targets MDM2          
IC50 0.09 μM          

Protocol

Kinase experiment [1]:

Binding assays

Competition assays were performed on a Biacore S51 (Biacore Inc., Piscataway, NJ). A Series S Sensor chip CM5 was derivatized for immobilization of a PentaHis antibody for capture of the His-tagged p53. The level of capture was ~ 200 response units (1 response unit corresponds to 1 pg of protein per mm2). The concentration of MDM2 protein was kept constant at 300 nM. Nutlin-3a was dissolved in DMSO at 10 mM and further diluted to make a concentration series of nutlin-3a in each MDM2 test sample. The assays were run at 25℃ in running buffer (10 mM Hepes, 0.15 M NaCl, 2% DMSO). MDM2-p53 binding in the presence of nutlin-3a was calculated as a percentage of binding in the absence of nutlin-3a and IC50 was calculated using Microsoft Excel.

Cell experiment [1]:

Cell lines

HCT116 and SW480 cells.

Preparation method

Soluble in DMSO > 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

1, 2, 4, 8, 16 μM; 8 h.

Applications

Nutlin-3a chiral induces the expression of MDM2 and p21 in HCT116 cells with wild-type p53. In HCT116, RKO, and SJSA-1 cells, nutlin-3a chiral (10, 20 or 30 μM) exhibits antiproliferative activity. In SJSA-1 osteosarcoma cells, nutlin-3a chiral (10 μM) induces apoptosis.

Animal experiment [1]:

Animal models

Nude mice bearing subcutaneous human cancer xenografts (SJSA-1).

Dosage form

200 mg/kg; twice daily for 20 days; administrated orally.

Application

Nutlin-3 inhibits tumor growth by 90%. The mice don’t lose significant weight and don’t show any grossabnormalities upon necropsy at the end of the treatment.

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.

References:

[1]. Vassilev LT, Vu BT, Graves B, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science, 2004, 303(5659): 844-848.

Nutlin-3a chiral Dilution Calculator

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Chemical Properties

Cas No. 675576-98-4 SDF Download SDF
Synonyms Nutlin-3a;Nutlin 3a
Chemical Name 4-[(4S,5R)-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 581.49
Solubility Soluble in DMSO > 10 mM Storage Store at -20°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Background

Nutlin-3 is a small-molecule inhibitor of MDM2 (mouse double minute 2) with IC50 value of 0.09μM [1].

Nutlin-3 binds MDM2 in the TP53-bindingpocket, thereby interfering with MDM2-directed TP53 degradation. This has been shown to cause cell cycle arrest, growth inhibitionand apoptosis in both solid tumors and lymphoid neoplasms.In mantle cell lymphoma(MCL), it is reported that Nutlin-3 can inhibit cell growth and activate apoptosis in bothwt-TP53(IC50 of 1 to 10μM) and mt-TP53(IC50 of 22.5μM) cells [2].

Nutlin-3 can also effectcell cycle in gastric cancer cell lines. It induces G1 arrest inMKN-45 and SNU-1 cell lines. In vitro assay shows Nutlin-3can enhance the antitumoreffects of conventional chemotherapeutic agents in several gastric cancer cell lines. And in in vivo assay, Nutlin-3 significantly inhibits the growth of xenograft tumors [3].

References:
[1] Lyubomir T.Vassilev et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.Science.2004, 303: 844-848.
[2] Yoko Tabe, Denise Sebasigari, Linhua Jin, et al.MDM2 Antagonist Nutlin-3 Displays Antiproliferative andProapoptotic Activity in Mantle Cell Lymphoma. Clin Cancer Res. 2009, 15:933-942.
[3] Shinji Endo,Kenji Yamato,Sachiko Hirai,Toshikazu Moriwaki,Kuniaki Fukuda,Hideo Suzuki,Masato Abei,Ichiro Nakagawa and IchinosukeHyodo.Potent in vitro and in vivo antitumor effects ofMDM2 inhibitor nutlin-3 in gastric cancer cells.Cancer Science. 2011, 102 (3): 605-613.