Allo-network drugs: harnessing allostery in cellular networks

TL;DR

This paper introduces the concept of allo-network drugs, expanding the scope of allosteric drugs to include effects across cellular networks, aiming for more targeted therapies with fewer side effects.

Contribution

It broadens the concept of allosteric drugs to allo-network drugs, proposing a new paradigm for systems-based drug design that targets cellular networks.

Findings

Allo-network drugs can propagate effects across multiple proteins.

They can achieve specific, limited system-level changes.

Potential for fewer side effects and lower toxicity.

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. Here, we propose 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 outlining a new paradigm in systems-based drug design.