NR APEV
AU Bach,S.; Talarek,N.; Andrieu,T.; Vierfond,J.M.; Mettey,Y.; Galons,H.; Dormont,D.; Meijer,L.; Cullin,C.; Blondel,M.
TI Isolation of drugs active against mammalian prions using a yeast-based screening assay
QU Nature Biotechnology 2003 Sep; 21(9): 1075-81
PT evaluation studies; journal article; validation studies
AB 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.
MH Animals; Cell Line, Tumor; Colony Count, Microbial/methods; Human; Mammals; Mice; Neuroblastoma; Phenanthridines/*chemistry/*isolation & purification/metabolism; Prions/*antagonists & inhibitors/*chemistry; Protein Interaction Mapping/*methods; Saccharomyces cerevisiae/classification/*isolation &; purification/*metabolism; Species Specificity; Support, Non-U.S. Gov't; Yeasts/classification/isolation & purification/metabolism
AD C.N.R.S., Station Biologique, Cell Cycle Laboratory, place Georges Teissier, 29680 ROSCOFF, Bretagne, France.
SP englisch
PO USA