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MedKoo CAT#: 406308
CAS#: 675576-98-4 (4S5R)
Description: Nutlin-3a, also known as SML 0580, 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.
MedKoo Cat#: 406308
Name: Nutlin-3a
CAS#: 675576-98-4 (4S5R)
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 (4S5R) 548472-68-0 (4R5S and 4S5R) 675576-97-3(4R5S Nutlin 3b)
Synonym: Nutlin3a; Nutlin 3a; Nutlin-3a; SML 0580; SML0580; SML-0580; (-)-Nutlin 3, (-)-Nutlin-3;
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
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).
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.
