Nutlin-3a
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406308

CAS#: 548472-68-0

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.


Price and Availability

Size
Price

100mg
USD 750
1g
USD 3250
Size
Price

200mg
USD 1350
2g
USD 4650
Size
Price

500mg
USD 2150
5g
USD 6950

Nutlin-3a, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 406308
Name: Nutlin-3a
CAS#: 548472-68-0
Chemical Formula: C30H30Cl2N4O4
Exact Mass: 580.16441
Molecular Weight: 581.49
Elemental Analysis: C, 61.97; H, 5.20; Cl, 12.19; N, 9.64; O, 11.01


Related CAS #: 675576-98-4   548472-68-0   675576-97-3.  

Synonym: Nutlin3a; Nutlin 3a; Nutlin-3a

IUPAC/Chemical Name: 4-((4S,5R)-4,5-bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one

InChi Key: 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 Code: O=C1NCCN(C(N2[C@H](C3=CC=C(Cl)C=C3)[C@H](C4=CC=C(Cl)C=C4)N=C2C5=CC=C(OC)C=C5OC(C)C)=O)C1


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

Nutlins are cis-imidazoline analogs which inhibit the interaction between MDM2 and tumour suppressor p53, and were discovered by screening a chemical library by Vassilev et al. Nutlin-1, Nutlin-2 and Nutlin-3 were all identified in the same screen, however Nutlin-3 is the compound most commonly used in anti-cancer studies. Inhibiting the interaction between mdm2 and p53 stabilizes p53 and is thought to selectively induce a growth-inhibiting state called senescence in cancer cells. These compounds are therefore thought to work best on tumors that contain normal or wild type p53.[citation needed] Nutlin-3 has been shown to affect the production of p53 within minutes. (source: http://en.wikipedia.org/wiki/Nutlin). 
   
 
 


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.

6: Retraction notice to "Epithelial cell adhesion molecule targeted nutlin-3a loaded immunonanoparticles for cancer therapy" [Acta Biomaterialia 7 (2011) 355–369]. Acta Biomater. 2013 Jun;9(6):7076. PubMed PMID: 23802319.

7: Luo H, Yount C, Lang H, Yang A, Riemer EC, Lyons K, Vanek KN, Silvestri GA, Schulte BA, Wang GY. Activation of p53 with Nutlin-3a radiosensitizes lung cancer cells via enhancing radiation-induced premature senescence. Lung Cancer. 2013 Aug;81(2):167-73. doi: 10.1016/j.lungcan.2013.04.017. Epub 2013 May 16. PubMed PMID: 23683497; PubMed Central PMCID: PMC3739976.

8: 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.

9: Zajkowicz A, Krześniak M, Matuszczyk I, Głowala-Kosińska M, Butkiewicz D, Rusin M. Nutlin-3a, an MDM2 antagonist and p53 activator, helps to preserve the replicative potential of cancer cells treated with a genotoxic dose of resveratrol. Mol Biol Rep. 2013 Aug;40(8):5013-26. doi: 10.1007/s11033-013-2602-7. Epub 2013 May 11. PubMed PMID: 23666059; PubMed Central PMCID: PMC3723979.

10: 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.