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Nutlin-3a (675576-98-4)

Nutlin-3a, the active enantiomer of Nutlin-3, inhibits the p53/MDM2 interaction with IC50 of 90 nM. Nutlin-3a is an inhibitor of MDM2 (human homolog of murine double minute 2)….

Not Intended for Therapeutic Use. For research use only.

CAS: 675576-98-4 Category

Nutlin-3a (675576-98-4) Description:

Nutlin-3a is an inhibitor of MDM2 (human homolog of murine double minute 2), which disrupts its interaction with p53, leading to the stabilization and activation of p53. Nutlin-3a activates the p53 pathway and efficiently induces apoptosis in tumours with amplified MDM2 gene and overexpression of MDM2 protein. Nutlin-3a is also a cis-imidazoline analog, which inhibits the interaction between the proteins p53 and MDM2. It is known that Nutlin-3a appears as the first peak during chiral purification of racemic Nutlin-3 (sc-45061). Studies indicate that Nutlin-3a amplifies the expression of p53 regulated genes and shows antiproliferative effects in cells containing functional p53. Nutlin-3a is a useful tool in studying the regulation of tumors in cells.

Nutlin-3a (675576-98-4) Specifications:

Product Name Nutlin-3a
Synonym Nutlin3a; Nutlin 3a; Nutlin-3a
Chemical Name (-)-4-(4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one
Drug Class Inhibitor
Purity ≥98% (HPLC)
CAS Number 675576-98-4
Molecular Formula C30H30Cl2N4O4
Molecular Weight 581.49
Monoisotopic Mass 580.16441 g/mol
MDL number MFCD14636430
InChIKey BDUHCSBCVGXTJM-WUFINQPMSA-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)/t27-,28+/m0/s1
SMILES CC(C)OC1=C(C=CC(=C1)OC)C2=N[[email protected]]([[email protected]](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(5 mg/mL)
Storage Temp.  -20°C
Shelf life >2 years if stored properly
Handling Protect from air and light
Application An inhibitor of p-53-MDM2 interaction

 


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RIDADR NONH for all modes of transport

References:

[1]. Pishas KI, Neuhaus SJ, Clayer MT, Schreiber AW, Lawrence DM, Perugini M, Whitfield RJ, Farshid G, Manavis J, Chryssidis S, Mayo BJ, Haycox RC, Ho K, Brown MP, D’Andrea RJ, Evdokiou A, Thomas DM, Desai J, Callen DF, Neilsen PM. Nutlin-3a efficacy in sarcoma predicted by transcriptomic and epigenetic profiling. Cancer Res. 2014 Feb 1;74(3):921-31. doi: 10.1158/0008-5472.CAN-13-2424. Epub 2013 Dec 13. PubMed PMID: 24336067.

[2]. Shukla KK, Kwon WS, Rahman MS, Park YJ, You YA, Pang MG. Nutlin-3a decreases male fertility via UQCRC2. PLoS One. 2013 Oct 9;8(10):e76959. doi: 10.1371/journal.pone.0076959. eCollection 2013. PubMed PMID: 24130818; PubMed Central PMCID: PMC3793967.

[3]. Bozzi F, Conca E, Laurini E, Posocco P, Lo Sardo A, Jocollè G, Sanfilippo R, Gronchi A, Perrone F, Tamborini E, Pelosi G, Pierotti MA, Maestro R, Pricl S, Pilotti S. In vitro and in silico studies of MDM2/MDMX isoforms predict Nutlin-3A sensitivity in well/de-differentiated liposarcomas. Lab Invest. 2013 Nov;93(11):1232-40. doi: 10.1038/labinvest.2013.107. Epub 2013 Sep 9. PubMed PMID: 24018792.

[4]. Anil B, Riedinger C, Endicott JA, Noble ME. The structure of an MDM2-Nutlin-3a complex solved by the use of a validated MDM2 surface-entropy reduction mutant. Acta Crystallogr D Biol Crystallogr. 2013 Aug; 69(Pt 8):1358-66. doi: 10.1107/S0907444913004459. Epub 2013 Jul 13. PubMed PMID: 23897459.

[5]. Fukumoto J, Lockey R, Kolliputi N. New hope for Nutlin-3a therapy for pulmonary arterial hypertension. Front Pharmacol. 2013 Jul 10;4:87. doi: 10.3389/fphar.2013.00087. eCollection 2013. PubMed PMID: 23847537; PubMed Central PMCID: PMC3706748.