Finding new tricks for old drugs: an efficient route for public-sector drug discovery

Nat Rev Drug Discov. 2005 Dec;4(12):1005-14. doi: 10.1038/nrd1900.


With the annotation of the human genome approaching completion, public-sector researchers - spurred in part by various National Institutes of Health Roadmap Initiatives - have become increasingly engaged in drug discovery and development efforts. Although large and diverse chemical libraries of 'drug-like' compounds can be readily screened to yield chemically novel scaffolds, transforming these 'chemical probes' into drugs is a daunting endeavour. A more efficient approach involves screening libraries of approved and off-patent medications; both phenotypic- and molecular target-based screening of 'old drugs' can readily yield compounds that could be immediately used in clinical trials. Using case studies, we describe how this approach has rapidly identified candidate medications suitable for clinical trials in disorders such as progressive multifocal leukoencephalopathy and amyotrophic lateral sclerosis. This approach has also led to the discovery of the molecular targets responsible for serious drug side effects, thereby allowing efficient 'counter-screening' to avoid these side effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Antipsychotic Agents / pharmacology
  • Drug Design*
  • Drug Evaluation, Preclinical / methods
  • Drug Therapy / economics
  • Drug Therapy / methods
  • Drug Therapy / trends*
  • Efficiency
  • Efficiency, Organizational* / economics
  • Efficiency, Organizational* / trends
  • Fenfluramine / adverse effects
  • Humans
  • Neuroprotective Agents / pharmacology
  • Phentermine / adverse effects
  • Public Sector / economics*
  • Public Sector / trends
  • Technology, Pharmaceutical / economics
  • Technology, Pharmaceutical / methods
  • Technology, Pharmaceutical / trends


  • Anti-Bacterial Agents
  • Antipsychotic Agents
  • Neuroprotective Agents
  • Fenfluramine
  • Phentermine