P53/MDM2 interaction

PiCKSLEY, S. M., et al.. The p53-MDM2 interaction in a cancer-prone family, and the identification of a novel therapeutic target. Acta Oncol, 1996, 35(4), 429-34. 

Duncan SJ, Williams DH, Ainsworth M, Martin S, Ford R, Wrigley SK (2002) On the Biosynthesis of an Inhibitor of the p53/MDM2 Interaction. Tetrahedron Lett 43 1075... 

Chen F, Yin H, Sebti BFS, Hamilton AD, Chen J. p53 alpha-Helix mimetics antagonize p53/MDM2 interaction and activate p53. Mol. Cancer Therap. 2005 4 1019-1025. 

Figure 4 Protein-protein and protein-DNA inhibition, (a) Examples of inhibitors of protein-DNA interactions, (b) p53 is bound by MDM2 and inhibits p53-dependent transcription. In some cancers, MDM2 is overexpressed and p53 is bound continuously by MDM2 despite cellular signals. Inhibitors can be used to disrupt this interface and regain p53 function. The structure of p53 activation domain bound to MDM2 (103). (c) Inhibitors of the p53-MDM2 interaction and of the TF Hap3p.

Chene P. Inhibiting the p53-MDM2 interaction an important target for cancer therapy. Nat. Rev. Cancer 2003 3 102-109. 

Klein C, Vassilev LT. Targeting the p53-MDM2 interaction to 139. treat cancer. Br. J. Cancer 2004 91 1415-1419. 

Galatin PS, Abraham DJ. A nonpeptidic sulfonamide inhibits the p53-mdm2 interaction and activates p53-dependent transcription in mdm2-overexpressing cells. J. Med. Chem. 2004 47 4163 165. 

Dudkina, A. S., and Lindsley, C. W. (2007) Small molecule protein-protein inhibitors of the p53-MDM2 interaction. Curr. Top. Med. Chem. 7, 952-960. 

Weber L (2010) Patented inhibitors of p53-Mdm2 interaction (2006-2008). Expert Opin Ther Patents 20 179-191... 

Galatin PS, Abraham DJ (2001) QSAR hydropathic analysis of inhibitors of the p53-mdm2 interaction. Proteins 45 169-175... 

Chlorofusin (52) was one of the major components produced by fermentation of Fusarium sp. 22026. The DELFIA-modified ELISA was used to guide to the purification of inhibitors of the p53/MDM2 interaction from these fermentation extracts. Chlorofusin was the most abundant inhibitory compound. Titration of purified chlorofusin in the... 

Chene P. Inhibition of p53-MDM2 interaction Targeting a protein-protein interface. Mol Cancer Res 2004 2 20-28. 

Figure S.S Examples for new p53 MDM2 interaction inhibitors from commercial sources [141].

Lauria, A., Tutone, M., Ippolito, M., Pantano, L.> 8c Almerico, A. M. (2010). Molecular modeling approaches in the discovery of new drugs for anti-cancer therapy The investigation of p53-MDM2 interaction and its inhibition by small molecules. Current Medicinal Chemistry, J7, 3142. 

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