Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 143, Issue -, Pages 1277-1300Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2017.10.021
Keywords
Dual-targeting; Multi-targeting; Proteomics; Bioinformatics; Polypharmacology
Categories
Funding
- Coordination for the Improvement of Higher Education Personnel [CAPES-Fiocruz-001/2012]
- Fundacao Oswaldo Cruz (Fiocruz) of Brasil
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Dual-targeting/Multi-targeting of oncoproteins by a single drug molecule represents an efficient, logical and alternative approach to drug combinations. An increasing interest in this approach is indicated by a steady upsurge in the number of articles on targeting dual/multi proteins published in the last 5 years. Combining different inhibitors that destiny specific single target is the standard treatment for cancer. A new generation of dual or multi-targeting drugs is emerging, where a single chemical entity can act on multiple molecular targets. Dual/Multi-targeting agents are beneficial for solving limited efficiencies, poor safety and resistant profiles of an individual target. Designing dual/multi-target inhibitors with predefined biological profiles present a challenge. The latest advances in bioinformatic tools and the availability of detailed structural information of target proteins have shown a way of discovering multi targeting molecules. This neoteric artifice that amalgamates the molecular docking of small molecules with protein-based common pharmacophore to design multi-targeting inhibitors is gaining great importance in anticancer drug discovery. Current review focus on the discoveries of dual targeting agents in cancer therapy using rational, computational, proteomic, bloinformatics and polypharmacological approach that enables the discovery and rational design of effective and safe multi-target anticancer agents. (C) 2017 Elsevier Masson SAS. All rights reserved.
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