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

Authors :
Andreas G. Tzakos
Demosthenes Fokas
Charlie Johannes
Vassilios Moussis
Eleftheria Hatzimichael
Evangelos Briasoulis
Source :
Molecules, Vol 16, Iss 6, Pp 4408-4427 (2011)
Publication Year :
2011
Publisher :
MDPI AG, 2011.

Abstract

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.

Details

Language :
English
ISSN :
14203049
Volume :
16
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.6b6600e96f4740eb8b2754695d288040
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules16064408