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Designed Multiple Ligands for Cancer Therapy

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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

Document Type: Research Article


Publication date: 2011-11-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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