Antiprion compounds that reduce PrPSc levels in dividing and stationary-phase cells

During prion diseases, a normally benign, host protein, denoted PrP , undergoes alternative folding into the aberrant isoform, PrP . We used ELISA to identify and confirm hits in order to develop leads that reduce PrP 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 (EC ), 102 had EC values between 1 and 10 μM and 50 had EC values o