Fig. 3.

Identification of a potent polyQ-aggregation inhibitor, C2-8. (A) Structures of three potent analogs (C2-8, C3-5, and C4-7) derived from focused libraries of compounds with structural similarity to primary hits. The IC₅₀ value of each compound in the PC12 cell assay (B) is noted. No cytotoxicity was observed using compound concentrations up to 10 μM. (B) C2-8, at 100 nM, (Lower) inhibits polyQ aggregation in 103Q-EGFP PC12 cells, as shown by fluorescence microscopy. Upper shows control (DMSO-treated) cells. (C) Immunodetection of insoluble recombinant HD 51Q trapped on the filter. Purified HF 51Q was incubated with solvent, C2-8, or Congo red (CR). (D) Quantification of results shown in C. Signal intensity from the sample incubated in the presence of the solvent alone was used as reference and set at 100%.