Innovation - A robustness-based approach to systems-oriented drug design

被引:350
作者
Kitano, Hiroaki [1 ]
机构
[1] Sony Comp Sci Labs Inc, Shinagawa Ku, Tokyo 1410022, Japan
[2] Syst Biol Inst, Tokyo 1500001, Japan
[3] Inst Canc Res, Dept Canc Syst Biol, Koutou Ku, Tokyo 1358550, Japan
基金
日本科学技术振兴机构;
关键词
D O I
10.1038/nrd2195
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:202 / 210
页数:9
相关论文
共 102 条
  • [1] Multiple weak hits confuse complex systems: A transcriptional regulatory network as an example
    Agoston, V
    Csermely, P
    Pongor, S
    [J]. PHYSICAL REVIEW E, 2005, 71 (05)
  • [2] Comparison of once-daily, niacin extended/release/lovastatin with standard doses of atorvastatin and simvastafin (The Advicor Versus Other Cholesterol-Modulating Agents Trial Evaluation [ADVOCATE])
    Bays, HE
    Dujovne, CA
    McGovern, ME
    White, TE
    Kashyap, ML
    Hutcheson, AG
    Crouse, JR
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 2003, 91 (06) : 667 - 672
  • [3] Robustness of the bistable behavior of a biological signaling feedback loop
    Bhalla, US
    Iyengar, R
    [J]. CHAOS, 2001, 11 (01) : 221 - 226
  • [4] Bifurcation analysis of a model of mitotic control in frog eggs
    Borisuk, MT
    Tyson, JJ
    [J]. JOURNAL OF THEORETICAL BIOLOGY, 1998, 195 (01) : 69 - 85
  • [5] Systematic discovery of multicomponent therapeutics
    Borisy, AA
    Elliott, PJ
    Hurst, NW
    Lee, MS
    Lehár, J
    Price, ER
    Serbedzija, G
    Zimmermann, GR
    Foley, MA
    Stockwell, BR
    Keith, CT
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (13) : 7977 - 7982
  • [6] Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial
    Bresalier, RS
    Sandler, RS
    Quan, H
    Bolognese, JA
    Oxenius, B
    Horgan, K
    Lines, C
    Riddell, R
    Morton, D
    Lanas, A
    Konstam, MA
    Baron, JA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (11) : 1092 - 1102
  • [7] Can cell systems biology rescue drug discovery?
    Butcher, EC
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2005, 4 (06) : 461 - 467
  • [8] Systems biology in drug discovery
    Butcher, EC
    Berg, EL
    Kunkel, EJ
    [J]. NATURE BIOTECHNOLOGY, 2004, 22 (10) : 1253 - 1259
  • [9] Highly optimized tolerance: Robustness and design in complex systems
    Carlson, JM
    Doyle, J
    [J]. PHYSICAL REVIEW LETTERS, 2000, 84 (11) : 2529 - 2532
  • [10] Complexity and robustness
    Carlson, JM
    Doyle, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 : 2538 - 2545