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A robustness-based approach to systems-oriented drug design

Nature Reviews Drug Discovery volume 6, pages 202–210 (2007)Cite this article

Abstract

Many potential drugs that specifically target a particular protein considered to underlie a given disease have been found to be less effective than hoped, or to cause significant side effects. The intrinsic robustness of living systems against various perturbations is a key factor that prevents such compounds from being successful. By studying complex network systems and reformulating control and communication theories that are well established in engineering, a theoretical foundation for a systems-oriented approach to more effectively control the robustness of living systems, particularly at the cellular level, could be developed. Here, I use examples that are based on existing drugs to illustrate the concept of robustness, and then discuss how a greater consideration of the importance of robustness could influence the design of new drugs that will be intended to control complex systems.

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Figure 1: Basic mechanisms for robustness.
Figure 2: A range of options for drug design.

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Acknowledgements

This research was supported in part by the Exploratory Research for Advanced Technology (ERATO) and the Solution-Oriented Research for Science and Technology (SORST) programs (Japan Science and Technology Agency), a New Energy and Industrial Technology Development Organization Grant (NEDO) of the Japanese Ministry of Economy, Trade and Industry (METI), and the Genome Network Project by the Ministry of Education, Culture, Sports, Science, and Technology.

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  1. Japan; and the Department of Cancer Systems Biology, Hiroaki Kitano is at Sony Computer Science Laboratories Inc., 3-14-13 Higashi-Gotanda, Shinagawa, Tokyo 141-0022, Japan; The Systems Biology Institute, Suite 6A M31 6-31-15 Jingumae, Shuibuya, Tokyo 150-0001, The Cancer Institute, 3-10-6 Ariake, Koutou-ku, Tokyo 135-8550, Japan. kitano@sbi.jp,

    Hiroaki Kitano

  2. The Systems Biology Institute, Suite 6A M31 6-31-15 Jingumae, Shuibuya, Tokyo 150-0001, Japan,

    Hiroaki Kitano

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Using multistage drugs to achieve efficacy and selectivity. (PDF 132 kb)

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The spread spectrum control problem and the long-tail control problem (PDF 120 kb)

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Kitano, H. A robustness-based approach to systems-oriented drug design. Nat Rev Drug Discov 6, 202–210 (2007). https://doi.org/10.1038/nrd2195

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