Key Points
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Drug combinations are highly useful for enhanced therapeutics.
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Understanding of their mechanisms facilitates the discovery of new multicomponent and multi-target therapeutics.
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This article describes the extensive investigation of the published literature on a large number of drug combinations from interaction and network perspectives, which reveals general and specific modes of action.
Abstract
Understanding the molecular mechanisms underlying synergistic, potentiative and antagonistic effects of drug combinations could facilitate the discovery of novel efficacious combinations and multi-targeted agents. In this article, we describe an extensive investigation of the published literature on drug combinations for which the combination effect has been evaluated by rigorous analysis methods and for which relevant molecular interaction profiles of the drugs involved are available. Analysis of the 117 drug combinations identified reveals general and specific modes of action, and highlights the potential value of molecular interaction profiles in the discovery of novel multicomponent therapies.
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Acknowledgements
We acknowledge the support from Academic Research Funds Singapore (R-148-000-081-112); National Natural Science Foundation of China (30772651, 30500107); Ministry of Science and Technology China (2006AA020400, 2006AA02Z317, 2004CB720103); and Science and Technology Commission of Shanghai Municipality (06PJ14072).
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Supplementary information
Supplementary information S1 (table)
Literature–reported pharmacodynamically synergistic drug combinations due to anti–counteractive actions, in which synergy has been determined by well established synergy/additive analysis methods and its molecular mechanism has been revealed. (PDF 759 kb)
Supplementary information S2 (table)
Literature–reported pharmacodynamically synergistic drug combinations due to complementary actions, in which synergy has been determined by well established synergy/additive analysis methods and its molecular mechanism has been revealed. (PDF 881 kb)
Supplementary information S3 (table)
Literature–reported pharmacodynamically synergistic drug combinations due to facilitating actions, in which synergy has been determined by well established synergy/additive analysis methods and its molecular mechanism has been revealed. (PDF 325 kb)
Supplementary information S4 (table)
Literature–reported pharmacodynamically additive drug combinations, in which additive action has been determined by well established synergy/additive analysis methods and its molecular mechanism has been revealed (PDF 470 kb)
Supplementary information S5 (table)
Literature–reported pharmacodynamically antagonistic drug combinations, in which antagonism has been determined by established methods and its molecular mechanism has been revealed. The antagonism of the listed drug combinations is due to interfering actions of the partner drugs in each combination. (PDF 274 kb)
Supplementary information S6 (table)
Literature–reported pharmacokinetically potentiative drug combinations, in which potentiative effect has been determined by established methods and its molecular mechanism has been revealed (PDF 440 kb)
Supplementary information S7 (table)
Literature–reported pharmacokinetically reductive drug combinations, in which reductive effect has been determined by established methods and its molecular mechanism has been revealed. (PDF 287 kb)
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Jia, J., Zhu, F., Ma, X. et al. Mechanisms of drug combinations: interaction and network perspectives. Nat Rev Drug Discov 8, 111–128 (2009). https://doi.org/10.1038/nrd2683
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DOI: https://doi.org/10.1038/nrd2683
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