Isolation of drugs active against mammalian prions using a yeast-based screening assay
Isolation of drugs active against mammalian prions using a yeast-based screening assay
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DOI：
10.1038/nbt855
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发表时间：
2003-09-01
影响因子：
46.9
通讯作者：
Blondel, M
中科院分区：
文献类型：
--
作者：
Bach, S;Talarek, N;Blondel, M
我们已经开发了一种快速的，基于酵母的，两步测定来筛选抗朊病毒药物。该方法使我们能够鉴定出几种有效对抗[PSI+]和[URE 3]表型的芽殖酵母朊病毒的化合物。这些抑制剂包括kastellpaolitines，一类新的化合物，和两个以前已知的分子，菲啶和6-氨基菲啶。两个有效的启动子的哺乳动物朊病毒的清除在体外，奎纳克林和氯丙嗪，这与kastellpaolitines共享结构相似性，也活跃在测定中。这里分离的化合物也有促进哺乳动物朊病毒清除的活性。这些结果验证了本方法作为鉴定新朊病毒抑制剂的有效高通量筛选方法，并且进一步表明控制朊病毒形成和/或维持的生化途径从酵母到人是保守的。
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.