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Publication date: November 2015 Source:European Journal of Cancer Supplements, Volume 13, Issue 1 Author(s): N. Barlev, O. Fedorova, L. Lezina, S. Piletsky Discovery of new pharmacologically active small molecules is an important and rapidly expanding area of modern molecular pharmacology. Given a limited number of proteins that are druggable, it is important to identify as many chemical effectors as possible to define the best regimen of anti-cancer therapy in each particular case. An E3 ubiquitin ligase, Mdm2, which mediates ubiquitin-dependent degradation of the critical tumor suppressor p53, is a promising target for small molecule inhibitors. Using a hybrid approach which combines the rational design of small molecules selected from the virtual library and the high-content screening using cancer cell lines we discovered several new inhibitors of the p53-Mdm2 interaction. These compounds were able to activate and stabilize the p53 protein causing massive apoptosis preferably in p53-positive cells at rates higher than the well-known inhibitor of Mdm2, Nutlin-3. The molecular mechanisms of their action will be discussed. As another example of rational design of potential anti-cancer drugs, we will talk about artificial nano-Matrix-Imprinted -Polymers (MIPs) that recognize the structure of peptides and other biological molecules and thus dubbed as “plastic antibodies”. We have generated such nanoparticles against the surface region of the oncogenic receptor, ...
Source: European Journal of Cancer Supplements - Category: Cancer & Oncology Source Type: research