Abstract
The concept of a single chemical entity with desirable activity at more than one biological target is an attractive one. Increasingly, multiple complex biochemical pathways are implicated in a variety of diseases including cancer. Successful treatment of these conditions often depends on pharmaceutical intervention at multiple pathways, with a combination of different drugs. Designed multiple ligands (DMLs) are drugs which act at multiple biomolecular targets. Numerous terms have been used to describe such ligands, including multiple-target directed ligands, heterodimers, promiscuous drugs and pan-agonists. However, although there are many reported examples of multiple-targeting anti-cancer agents, no review of these has been presented to date. A huge variety of biological signalling-pathways, proteins and enzymes are currently targeted and implicated in the pathogenesis of cancer. This review will provide an overview of reported designed multiple ligands for cancer and an exploration of the advantages and drawbacks of such compounds. The review also provides brief commentaries on the biological processes and proteins that are currently targeted in cancer therapy and the potential for dual or triple targeting of these with designed multiple ligands.
Keywords: Cancer, Chemotherapy, Combination therapy, Conjugate, Designed multiple ligand, Dual-target, Enzyme inhibition, Multi-target, Multikinase inhibitors, Network pharmacology, Polypharmacy, Selectivity
Current Medicinal Chemistry
Title: Designed Multiple Ligands for Cancer Therapy
Volume: 18 Issue: 31
Author(s): N. M. O'Boyle and M. J. Meegan
Affiliation:
Keywords: Cancer, Chemotherapy, Combination therapy, Conjugate, Designed multiple ligand, Dual-target, Enzyme inhibition, Multi-target, Multikinase inhibitors, Network pharmacology, Polypharmacy, Selectivity
Abstract: The concept of a single chemical entity with desirable activity at more than one biological target is an attractive one. Increasingly, multiple complex biochemical pathways are implicated in a variety of diseases including cancer. Successful treatment of these conditions often depends on pharmaceutical intervention at multiple pathways, with a combination of different drugs. Designed multiple ligands (DMLs) are drugs which act at multiple biomolecular targets. Numerous terms have been used to describe such ligands, including multiple-target directed ligands, heterodimers, promiscuous drugs and pan-agonists. However, although there are many reported examples of multiple-targeting anti-cancer agents, no review of these has been presented to date. A huge variety of biological signalling-pathways, proteins and enzymes are currently targeted and implicated in the pathogenesis of cancer. This review will provide an overview of reported designed multiple ligands for cancer and an exploration of the advantages and drawbacks of such compounds. The review also provides brief commentaries on the biological processes and proteins that are currently targeted in cancer therapy and the potential for dual or triple targeting of these with designed multiple ligands.
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Cite this article as:
M. O'Boyle N. and J. Meegan M., Designed Multiple Ligands for Cancer Therapy, Current Medicinal Chemistry 2011; 18 (31) . https://dx.doi.org/10.2174/092986711797535344
DOI https://dx.doi.org/10.2174/092986711797535344 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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