Therapeutic selectivity and the multi-node drug target.

摘要: Drug combinations are an increasingly favored strategy for increasing therapeutic windows potential drugs, but enthusiasm this approach is tempered by concerns that synergy will too often be mirrored synergistic toxicity. Here we review our recent experimental results and numerical simulations establish the context-specificity of combinations. Thus systematic testing chemical in cell-based disease models can preferentially discover synergies with beneficial selectivity. For anti-inflammatory combination, demonstrate how such selective achieved through differential expression its targets cells associated toxic effects, validate combination's relevance animals. The narrower context specificity creates many new opportunities therapeutically relevant selectivity, reinforces realization most useful paradigm a drug target set biomolecules cooperate to produce response reduced side effects.