title: Allo-network drugs: harnessing allostery in cellular networks.
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.
authors.affiliation: Center for Cancer Research Nanobiology Program, Science Applications International Corporation-Frederick, National Cancer Institute-Frederick, Frederick, MD 21702, USA. ruthnu@helix.nih.gov
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Tsai
authors.forename: Peter
authors.initials: P
authors.lastname: Csermely
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects*; D000818:Animals; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004798:Enzymes / Q000737:chemistry*; D006801:Humans; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D004798:Enzymes