Allo-network drugs: harnessing allostery in cellular networks

• DOI: 10.1016/j.tips.2011.08.004
• Publication Date: 2011-09-18T00:25:23Z
• Authors: Ruth Nussinov; Chung-Jung Tsai; Peter Csermely
• Keywords: 0301 basic medicine; 0303 health sciences; Molecular Networks (q-bio.MN); Enzymes; 3. Good health; 03 medical and health sciences; Allosteric Regulation; FOS: Biological sciences; Animals; Humans; Quantitative Biology - Molecular Networks; Molecular Targeted Therapy; Enzyme Inhibitors; Signal Transduction

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.<br/>14 pages, 4 figures, 69 references, a cover story of the 2011 December issue of Trends in Pharmacological Sciences<br/>