Nutlin-1

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 563627

CAS#: 548472-58-8

Description: Nutlin-1 is a p53-MDM2 binding inhibitor, p-Glycoprotein (p-gp) transport substrate, and antitumor agent.


Price and Availability

Size
Price

Size
Price

Size
Price

Nutlin-1 is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

img

Theoretical Analysis

MedKoo Cat#: 563627
Name: Nutlin-1
CAS#: 548472-58-8
Chemical Formula: C32H34Cl2N4O4
Exact Mass: 608.1957
Molecular Weight: 609.54
Elemental Analysis: C, 63.06; H, 5.62; Cl, 11.63; N, 9.19; O, 10.50


Synonym: Nutlin-1; Nutlin 1; Nutlin1;

IUPAC/Chemical Name: cis-1-[4-[[4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydroimidazol-1-yl]carbonyl]piperazin-1-yl]ethanone

InChi Key: IYDMGGPKSVWQRT-IHLOFXLRSA-N

InChi Code: InChI=1S/C32H34Cl2N4O4/c1-20(2)42-28-19-26(41-4)13-14-27(28)31-35-29(22-5-9-24(33)10-6-22)30(23-7-11-25(34)12-8-23)38(31)32(40)37-17-15-36(16-18-37)21(3)39/h5-14,19-20,29-30H,15-18H2,1-4H3/t29-,30+/m1/s1

SMILES Code: CC(N1CCN(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)CC1)=O


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

Shelf Life:
>3 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:
2934.99.03.00


References

1: Cao D, Chu WK, Ng TK, Yip YWY, Young AL, Pang CP, Jhanji V. Cellular Proliferation and Migration of Human Pterygium Cells: Mitomycin Versus Small-Molecule Inhibitors. Cornea. 2018 Jun;37(6):760-766. doi: 10.1097/ICO.0000000000001569. PubMed PMID: 29595761.

2: da Mota MF, de Carvalho FS, de Ávila RI, de Ávila PHM, Cortez AP, Menegatti R, Sabino JR, Dos Santos TRM, Gomes SA, da Cunha LC, Valadares MC. LQFM030 reduced Ehrlich ascites tumor cell proliferation and VEGF levels. Life Sci. 2018 May 15;201:1-8. doi: 10.1016/j.lfs.2017.12.029. Epub 2017 Dec 24. PubMed PMID: 29278686.

3: Hu C, Gao Y, Du W. Design, Synthesis, and Biological Evaluation of Pyrazole Derivatives. Chem Biol Drug Des. 2016 May;87(5):673-9. doi: 10.1111/cbdd.12699. Epub 2016 Jan 11. PubMed PMID: 26648479.

4: Zubbair Malik M, Ali S, Alam MJ, Ishrat R, Brojen Singh RK. Dynamics of p53 and Wnt cross talk. Comput Biol Chem. 2015 Dec;59 Pt B:55-66. doi: 10.1016/j.compbiolchem.2015.07.014. Epub 2015 Aug 23. PubMed PMID: 26375870.

5: Shuvalov OY, Fedorova OA, Petukhov AV, Daks AA, Vasilieva EA, Grigorieva TA, Ivanov GS, Barlev NA. [NEGATIVE REGULATORS OF TUMOR SUPPRESSOR P53 IN THE CONTEXT OF ANTICANCER THERAPY]. Tsitologiia. 2015;57(12):847-54. Review. Russian. PubMed PMID: 26995961.

6: Puszynski K, Gandolfi A, d'Onofrio A. The pharmacodynamics of the p53-Mdm2 targeting drug Nutlin: the role of gene-switching noise. PLoS Comput Biol. 2014 Dec 11;10(12):e1003991. doi: 10.1371/journal.pcbi.1003991. eCollection 2014 Dec. Erratum in: PLoS Comput Biol. 2015 Mar;11(3):e1004215. PubMed PMID: 25504419; PubMed Central PMCID: PMC4263360.

7: Golubovskaya VM, Ho B, Conroy J, Liu S, Wang D, Cance WG. Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex. Cancers (Basel). 2014 Jan 21;6(1):166-78. doi: 10.3390/cancers6010166. PubMed PMID: 24452144; PubMed Central PMCID: PMC3980603.

8: Jones RJ, Bjorklund CC, Baladandayuthapani V, Kuhn DJ, Orlowski RZ. Drug resistance to inhibitors of the human double minute-2 E3 ligase is mediated by point mutations of p53, but can be overcome with the p53 targeting agent RITA. Mol Cancer Ther. 2012 Oct;11(10):2243-53. doi: 10.1158/1535-7163.MCT-12-0135. Epub 2012 Aug 28. PubMed PMID: 22933706; PubMed Central PMCID: PMC3469746.

9: Hu C, Dou X, Wu Y, Zhang L, Hu Y. Design, synthesis and CoMFA studies of N1-amino acid substituted 2,4,5-triphenyl imidazoline derivatives as p53-MDM2 binding inhibitors. Bioorg Med Chem. 2012 Feb 15;20(4):1417-24. doi: 10.1016/j.bmc.2012.01.003. Epub 2012 Jan 9. PubMed PMID: 22273545.

10: Li X, Gilkes D, Li B, Cheng Q, Pernazza D, Lawrence H, Lawrence N, Chen J. Abnormal MDMX degradation in tumor cells due to ARF deficiency. Oncogene. 2012 Aug 9;31(32):3721-32. doi: 10.1038/onc.2011.534. Epub 2011 Nov 28. PubMed PMID: 22120712; PubMed Central PMCID: PMC3290737.

11: Gasilova N, Nazabal A. Monitoring ligand modulation of protein-protein interactions by chemical cross-linking and High-Mass MALDI mass spectrometry. Methods Mol Biol. 2012;803:219-29. doi: 10.1007/978-1-61779-364-6_15. PubMed PMID: 22065228.

12: Hu C, Li X, Wang W, Zhang L, Tao L, Dong X, Sheng R, Yang B, Hu Y. Design, synthesis, and biological evaluation of imidazoline derivatives as p53-MDM2 binding inhibitors. Bioorg Med Chem. 2011 Sep 15;19(18):5454-61. doi: 10.1016/j.bmc.2011.07.050. Epub 2011 Jul 30. PubMed PMID: 21855354.

13: Renault VM, Thekkat PU, Hoang KL, White JL, Brady CA, Kenzelmann Broz D, Venturelli OS, Johnson TM, Oskoui PR, Xuan Z, Santo EE, Zhang MQ, Vogel H, Attardi LD, Brunet A. The pro-longevity gene FoxO3 is a direct target of the p53 tumor suppressor. Oncogene. 2011 Jul 21;30(29):3207-21. doi: 10.1038/onc.2011.35. Epub 2011 Mar 21. PubMed PMID: 21423206; PubMed Central PMCID: PMC3136551.

14: Saha MN, Jiang H, Mukai A, Chang H. RITA inhibits multiple myeloma cell growth through induction of p53-mediated caspase-dependent apoptosis and synergistically enhances nutlin-induced cytotoxic responses. Mol Cancer Ther. 2010 Nov;9(11):3041-51. doi: 10.1158/1535-7163.MCT-10-0471. Epub 2010 Nov 9. PubMed PMID: 21062913.

15: Daftuar L, Zhu Y, Prives C. Ribosomal protein L37 and the p53 network. Cell Cycle. 2010 Nov 1;9(21):4259. doi: 10.4161/cc.9.21.13527. Epub 2010 Nov 1. PubMed PMID: 21057197.

16: Salerno E, Yuan Y, Scaglione BJ, Marti G, Jankovic A, Mazzella F, Laurindo MF, Despres D, Baskar S, Rader C, Raveche E. The New Zealand black mouse as a model for the development and progression of chronic lymphocytic leukemia. Cytometry B Clin Cytom. 2010;78 Suppl 1:S98-109. doi: 10.1002/cyto.b.20544. PubMed PMID: 20839343; PubMed Central PMCID: PMC2963456.

17: Zhang L, Yan Y, Zhu D, Yang W, Wang W, Hu Y, Yang B, He Q. Nutlin-1 strengthened anti-proliferation and differentiation-inducing activity of ATRA in ATRA-treated p-glycoprotein deregulated human myelocytic leukemia cells. Invest New Drugs. 2012 Feb;30(1):37-47. doi: 10.1007/s10637-010-9512-5. Epub 2010 Aug 5. PubMed PMID: 20686816.

18: Strano S, Blandino G. Stability strengths oncogenic activity. Cell Cycle. 2010 Apr 15;9(8):1458-9. Epub 2010 Apr 15. PubMed PMID: 20421715.

19: Huart AS, MacLaine NJ, Meek DW, Hupp TR. CK1alpha plays a central role in mediating MDM2 control of p53 and E2F-1 protein stability. J Biol Chem. 2009 Nov 20;284(47):32384-94. doi: 10.1074/jbc.M109.052647. Epub 2009 Sep 15. PubMed PMID: 19759023; PubMed Central PMCID: PMC2781653.

20: Zhang L, Zhang J, Hu C, Cao J, Zhou X, Hu Y, He Q, Yang B. Efficient activation of p53 pathway in A549 cells exposed to L2, a novel compound targeting p53-MDM2 interaction. Anticancer Drugs. 2009 Jul;20(6):416-24. PubMed PMID: 19579266.