Allo-network drugs: Harnessing allostery in cellular networks

Ruth Nussinov, Chung Jung Tsai, Peter Csermely

Research output: Contribution to journalReview articlepeer-review

Abstract

Allosteric drugs are increasingly used because they produce fewer side effects. Allosteric signal propagation does not stop at the 'end' of a protein, but may be dynamically transmitted across the cell. We propose here that the concept of allosteric drugs can be broadened to 'allo-network drugs' - whose effects can propagate either within a protein, or across several proteins, to enhance or inhibit specific interactions along a pathway. We posit that current allosteric drugs are a special case of allo-network drugs, and suggest that allo-network drugs can achieve specific, limited changes at the systems level, and in this way can achieve fewer side effects and lower toxicity. Finally, we propose steps and methods to identify allo-network drug targets and sites that outline a new paradigm in systems-based drug design.

Original languageEnglish
Pages (from-to)686-693
Number of pages8
JournalTrends in Pharmacological Sciences
Volume32
Issue number12
DOIs
StatePublished - Dec 2011

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