Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1783375481056264192 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6264371 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT tzakosandreasg targetingoncogenicproteinproteininteractionsbydiversityorientedsynthesisandcombinatorialchemistryapproaches AT fokasdemosthenes targetingoncogenicproteinproteininteractionsbydiversityorientedsynthesisandcombinatorialchemistryapproaches AT johannescharlie targetingoncogenicproteinproteininteractionsbydiversityorientedsynthesisandcombinatorialchemistryapproaches AT moussisvassilios targetingoncogenicproteinproteininteractionsbydiversityorientedsynthesisandcombinatorialchemistryapproaches AT hatzimichaeleleftheria targetingoncogenicproteinproteininteractionsbydiversityorientedsynthesisandcombinatorialchemistryapproaches AT briasoulisevangelos targetingoncogenicproteinproteininteractionsbydiversityorientedsynthesisandcombinatorialchemistryapproaches |