Novel compounds lowering the cellular isoform of the human prion protein in cultured human cells.

ABSTRACT:

Purpose

Previous studies showed that lowering PrP(C) concomitantly reduced PrP(Sc) in the brains of mice inoculated with prions. We aimed to develop assays that measure PrP(C) on the surface of human T98G glioblastoma and IMR32 neuroblastoma cells. Using these assays, we sought to identify chemical hits, confirmed hits, and scaffolds that potently lowered PrP(C) levels in human brains cells, without lethality, and that could achieve drug concentrations in the brain after oral or intraperitoneal dosing in mice.

Methods

We utilized HTS ELISA assays to identify small molecules that lower PrP(C) levels by ≥30% on the cell surface of human glioblastoma (T98G) and neuroblastoma (IMR32) cells.

Results

From 44,578 diverse chemical compounds tested, 138 hits were identified by

SUBMITTER: Silber BM 

PROVIDER: S-EPMC3984052 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature