A robustness-based approach to systems-oriented drug design

Nat Rev Drug Discov. 2007 Mar;6(3):202-10. doi: 10.1038/nrd2195. Epub 2007 Feb 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Proliferation / drug effects*
  • Communicable Diseases / drug therapy
  • Communicable Diseases / pathology
  • Drug Design*
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Models, Theoretical
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Pharmaceutical Preparations / administration & dosage*
  • Signal Transduction / drug effects*
  • Technology, Pharmaceutical / methods

Substances

  • Pharmaceutical Preparations