ArticleBioorganic & medicinal chemistry2013
Antiprion compounds that reduce PrP(Sc) levels in dividing and stationary-phase cells.
Article in Bioorganic & medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 20 citations in OpenAlex.
- Enhanced lysosomal activity prevents infection with PrPThe Journal of biological chemistry · 2026Article
- Genetically engineered cellular models of prion propagation.Cell and tissue research · 2023Review
- Aminoquinolones and Their Benzoquinone Dimer Hybrids as Modulators of Prion Protein Conversion.Molecules (Basel, Switzerland) · 2022Article
- Carnosic Acid and Carnosol Display Antioxidant and Anti-Prion Properties in In Vitro and Cell-Free Models of Prion Diseases.Antioxidants (Basel, Switzerland) · 2022Article
- Biology and Genetics of PrP Prion Strains.Cold Spring Harbor perspectives in medicine · 2017Review
- Developing Therapeutics for PrP Prion Diseases.Cold Spring Harbor perspectives in medicine · 2017Review
- Optimization of Aryl Amides that Extend Survival in Prion-Infected Mice.The Journal of pharmacology and experimental therapeutics · 2016Article
- Biaryl amides and hydrazones as therapeutics for prion disease in transgenic mice.The Journal of pharmacology and experimental therapeutics · 2013Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
During prion diseases, a normally benign, host protein, denoted PrP(C), undergoes alternative folding into the aberrant isoform, PrP(Sc). We used ELISA to identify and confirm hits in order to develop leads that reduce PrP(Sc) in prion-infected dividing and stationary-phase mouse neuroblastoma (ScN2a-cl3) cells. We tested 52,830 diverse small molecules in dividing cells and 49,430 in stationary-phase cells. This led to 3100 HTS and 970 single point confirmed (SPC) hits in dividing cells, 331 HTS and 55 confirmed SPC hits in stationary-phase cells as well as 36 confirmed SPC hits active in both. Fourteen chemical leads were identified from confirmed SPC hits in dividing cells and three in stationary-phase cells. From more than 682 compounds tested in concentration-effect relationships in dividing cells to determine potency (EC50), 102 had EC50 values between 1 and 10 μM and 50 had EC50 values of <1 μM; none affected cell viability. We observed an excellent correlation between EC50 values determined by ELISA and Western immunoblotting for 28 representative compounds in dividing cells (R(2)=0.75; p <0.0001). Of the 55 confirmed SPC hits in stationary-phase cells, 23 were piperazine, indole, or urea leads. The EC50 values of one indole in stationary-phase and dividing ScN2a-cl3 cells were 7.5 and 1.6 μM, respectively. Unexpectedly, the number of hits in stationary-phase cells was ~10% of that in dividing cells. The explanation for this difference remains to be determined.
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Registered trials
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