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Nutlin-3 (890090-75-2)

Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM; stabilizes p73 in p53-deficient cells…

Not Intended for Therapeutic Use. For research use only.

CAS: 890090-75-2 Category

Nutlin-3 (890090-75-2) Description:

Nutlin-3, the racemic and most commonly used form of nutlin, inhibits p53-MDM2 interaction. It has shown ability to induce the expression of p53-regulated genes and exhibits potent antiproliferative activity in cells with functional p53, but not in cells with mutated p53. When in combination with perifosine, anti-leukaemic activity has been observed. High N-MYC (MycN) expression has been induced in non-N-MYC-amplified neuroblastoma cells when treated with the combination of nutlin-3 and doxorubicin (sc-200923).

Nutlin 3 is also a small-molecule inhibitor that acts to inhibit MDM2 binding to p53 and subsequent p53-dependent DNA damage signaling. As a single agent, Nutlin 3 (2-10 μM) stabilizes p53 and p21WAF levels and is toxic to WTp53-22RV1 cells (IC50, 4.3 μM) but has minimal toxicity toward p53-deficient cells (IC50, >10 μM). Nutlin 3 induces p53 and p21WAF expression in a dose-dependent manner in 22RV1 cells. Short-term cell cycle assays show that, at a dose of 10 μM, Nutlin 3 increasea slightly the G1-phase fraction and decreasea S-phase fraction of all three cell lines.

Nutlin-3 (890090-75-2) Specifications:

Product Name Nutlin-3
Synonym 548472-68-0; 890090-75-2; Nutlin 3
Chemical Name (±)-4-[4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxy-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-2-one
Drug Class Inhibitor
Purity ≥98% (HPLC)
CAS Number 890090-75-2
Molecular Formula C30H30Cl2N4O4
Molecular Weight 581.494
Monoisotopic Mass 580.164g/mol
MDL number MFCD07784509
InChIKey BDUHCSBCVGXTJM-UHFFFAOYSA-N
InChi Code InChI=1S/C30H30Cl2N4O4/c1-18(2)40-25-16-23(39-3)12-13-24(25)29-34-27(19-4-8-21(31)9-5-19)28(20-6-10-22(32)11-7-20)36(29)30(38)35-15-14-33-26(37)17-35/h4-13,16,18,27-28H,14-15,17H2,1-3H3,(H,33,37)
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
Form Solid Powder
Color White to off-white
Solubility  Soluble in DMSO (~20 mg/ml)
Storage Temp.  -20°C
Shelf life >2 years if stored properly
Handling Protect from air and light
Application Inhibits p53-MDM2 interaction

 


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RIDADR NONH for all modes of transport

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.

[2]. Zhang Y, et al. Inauhzin and Nutlin3 synergistically activate p53 and suppress tumor growth.Cancer Biol Ther. Cancer Biol Ther. 2012 Aug;13(10):915-24.

[3]. Supiot S, et al. Nutlin-3 radiosensitizes hypoxic prostate cancer cells independent of p53. Mol Cancer Ther. 2008 Apr;7(4):993-9.

[4]. Pishas KI, Neuhaus SJ, Clayer MT, Adwal A, Brown MP, Evdokiou A, Callen DF, Neilsen PM. Pre-activation of the p53 pathway through Nutlin-3a sensitises sarcomas to drozitumab therapy. Oncol Rep. 2013 Jul;30(1):471-7. doi: 10.3892/or.2013.2454. Epub 2013 May 13. PubMed PMID: 23670273.

[5]. Janouskova H, Ray AM, Noulet F, Lelong-Rebel I, Choulier L, Schaffner F, Lehmann M, Martin S, Teisinger J, Dontenwill M. Activation of p53 pathway by Nutlin-3a inhibits the expression of the therapeutic target α5 integrin in colon cancer cells. Cancer Lett. 2013 Aug 19;336(2):307-18. doi: 10.1016/j.canlet.2013.03.018. Epub 2013 Mar 21. PubMed PMID: 23523610.