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Targeting Oncogenic Protein-Protein Interactions by Diversity Oriented Synthesis and Combinatorial Chemistry Approaches

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 deve...

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Autores principales: Tzakos, Andreas G., Fokas, Demosthenes, Johannes, Charlie, Moussis, Vassilios, Hatzimichael, Eleftheria, Briasoulis, Evangelos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264371/
https://www.ncbi.nlm.nih.gov/pubmed/21623312
http://dx.doi.org/10.3390/molecules16064408
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author Tzakos, Andreas G.
Fokas, Demosthenes
Johannes, Charlie
Moussis, Vassilios
Hatzimichael, Eleftheria
Briasoulis, Evangelos
author_facet Tzakos, Andreas G.
Fokas, Demosthenes
Johannes, Charlie
Moussis, Vassilios
Hatzimichael, Eleftheria
Briasoulis, Evangelos
author_sort Tzakos, Andreas G.
collection PubMed
description 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.
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spelling pubmed-62643712018-12-10 Targeting Oncogenic Protein-Protein Interactions by Diversity Oriented Synthesis and Combinatorial Chemistry Approaches Tzakos, Andreas G. Fokas, Demosthenes Johannes, Charlie Moussis, Vassilios Hatzimichael, Eleftheria Briasoulis, Evangelos Molecules Review 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. MDPI 2011-05-27 /pmc/articles/PMC6264371/ /pubmed/21623312 http://dx.doi.org/10.3390/molecules16064408 Text en © 2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Tzakos, Andreas G.
Fokas, Demosthenes
Johannes, Charlie
Moussis, Vassilios
Hatzimichael, Eleftheria
Briasoulis, Evangelos
Targeting Oncogenic Protein-Protein Interactions by Diversity Oriented Synthesis and Combinatorial Chemistry Approaches
title Targeting Oncogenic Protein-Protein Interactions by Diversity Oriented Synthesis and Combinatorial Chemistry Approaches
title_full Targeting Oncogenic Protein-Protein Interactions by Diversity Oriented Synthesis and Combinatorial Chemistry Approaches
title_fullStr Targeting Oncogenic Protein-Protein Interactions by Diversity Oriented Synthesis and Combinatorial Chemistry Approaches
title_full_unstemmed Targeting Oncogenic Protein-Protein Interactions by Diversity Oriented Synthesis and Combinatorial Chemistry Approaches
title_short Targeting Oncogenic Protein-Protein Interactions by Diversity Oriented Synthesis and Combinatorial Chemistry Approaches
title_sort targeting oncogenic protein-protein interactions by diversity oriented synthesis and combinatorial chemistry approaches
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6264371/
https://www.ncbi.nlm.nih.gov/pubmed/21623312
http://dx.doi.org/10.3390/molecules16064408
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