Nutlin-3

Reference

• Nutlin-3 enhances the bortezomib sensitivity of p53-defective cancer cells by inducing paraptosis
  • D.M. Lee, I.Y. Kim, M.J. Seo, M.R. Kwon, K.S. Choi, Exp. Mol. Med. 2017, 49, e365.


Application
Nutilin-3: A Small-Molecule Inhibitor of MDM2-P53 Protein-Protein Interaction
Tumor suppress protein p53 is an attractive target for cancer research because it can be functionally activated to eradicate tumors. Mouse double minute 2 homolog (MDM2) is a protein found in many human tumors, and binds the p53 with high affinity and negative modulates p53 transcriptional activity and stability. Nutilin-3 is a small-molecule inhibitor of MDM2-p53 protein-protein interaction. Nutilin-3 binds MDM2 in the p53-binding pocket and activate the p53 pathway in tumor cells, leading to cell cycle arrest, apoptosis, and growth inhibition of tumor cells. (The product is for research purpose only.)

References

• In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
  • L. T. Vassilev, B. T. Vu, B. Graves, D. Carvajal, F. Podlaski, Z. Filipovic, N. Kong, U. Kammlott, C. Lukacs, C. Klein, N. Fotouhi, E. A. Liu, Science 2004, 303, 844.
• Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy
  • C. Tovar, J. Rosinski, Z. Filipovic, B. Higgins, K. Kolinsky, H. Hilton, X. Zhao, B. T. Vu, W. Qing, K. Packman, O. Myklebost, D. C. Heimbrook, L. T. Vassilev, Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 1888.
• Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy (a review)
  • S. Shangary, S. Wang, Annu. Rev. Pharmacol. Toxicol. 2009, 49, 223.
• Recent advances in the therapeutic perspectives of nutlin-3 (a review)
  • P. Secchiero, R. Bosco, C. Celeghini, G. Zauli, Curr. Pharm. Des. 2011, 17, 569.