Isolation of drugs active against mammalian prions using a yeast-based screening assay

Nat Biotechnol. 2003 Sep;21(9):1075-81. doi: 10.1038/nbt855. Epub 2003 Aug 10.


We have developed a rapid, yeast-based, two-step assay to screen for antiprion drugs. The method allowed us to identify several compounds effective against budding yeast prions responsible for the [PSI+] and [URE3] phenotypes. These inhibitors include the kastellpaolitines, a new class of compounds, and two previously known molecules, phenanthridine and 6-aminophenanthridine. Two potent promoters of mammalian prion clearance in vitro, quinacrine and chlorpromazine, which share structural similarities with the kastellpaolitines, were also active in the assay. The compounds isolated here were also active in promoting mammalian prion clearance. These results validate the present method as an efficient high-throughput screening approach to identify new prion inhibitors and furthermore suggest that biochemical pathways controlling prion formation and/or maintenance are conserved from yeast to humans.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Colony Count, Microbial / methods
  • Humans
  • Mammals
  • Mice
  • Neuroblastoma
  • Phenanthridines / chemistry*
  • Phenanthridines / isolation & purification*
  • Phenanthridines / metabolism
  • Prions / antagonists & inhibitors*
  • Prions / chemistry*
  • Protein Interaction Mapping / methods*
  • Saccharomyces cerevisiae / classification
  • Saccharomyces cerevisiae / isolation & purification*
  • Saccharomyces cerevisiae / metabolism*
  • Species Specificity
  • Yeasts / classification
  • Yeasts / isolation & purification
  • Yeasts / metabolism


  • Phenanthridines
  • Prions