Targeting Oncogenic Protein-Protein Interactions by Diversity Oriented Synthesis and Combinatorial Chemistry Approaches (Journal article)

Tzakos, A. G./ Fokas, D./ Johannes, C./ Moussis, V./ Hatzimichael, E./ Briasoulis, E.


We are currently witnessing a decline in the development of efficient new anticancer drugs, despite the salient efforts made on all fronts of cancer drug discovery. This trend presumably relates to the substantial heterogeneity and the inherent biological complexity of cancer, which hinder drug development success. Protein-protein interactions (PPIs) are key players in numerous cellular processes and aberrant interruption of this complex network provides a basis for various disease states, including cancer. Thus, it is now believed that cancer drug discovery, in addition to the design of single-targeted bioactive compounds, should also incorporate diversity-oriented synthesis (DOS) and other combinatorial strategies in order to exploit the ability of multi-functional scaffolds to modulate multiple protein-protein interactions (biological hubs). Throughout the review, we highlight the chemistry driven approaches to access diversity space for the discovery of small molecules that disrupt oncogenic PPIs, namely the p53-Mdm2, Bcl-2/Bcl-xL-BH3, Myc-Max, and p53-Mdmx/Mdm2 interactions.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας
Keywords: diversity-oriented synthesis,combinatorial chemistry,protein-protein interactions,cancer,small-molecule antagonists,bcl-2 family proteins,cancer-therapy,c-myc,natural-products,drug discovery,p53 pathway,epigenetic therapy,breast-cancer,inhibitors
URI: http://olympias.lib.uoi.gr/jspui/handle/123456789/9551
ISSN: 1420-3049
Link: <Go to ISI>://000292032700009
http://www.mdpi.com/1420-3049/16/6/4408/pdf
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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