Figure 5.

High-throughput screen of a Food and Drug Administration–approved drug library for copper-only SOD5 inhibitors. A, approximately 900 compounds were tested at 10 μm for inhibition of Cu,Zn-SOD1 (blue) or copper-only SOD5 (red) using the high-throughput WST-1 assay of Fig. 3. The x axis numbers refer to an assigned number for each compound in the library. SOD5-selective inhibitors are labeled and circled. †, two compounds (magnesium carbonate and dimenhydrinate) appeared to have selective inhibition against SOD5 in the initial screen, but inhibition was not reproducible in follow-up studies. Results are the average of duplicate samples. B–E, SOD5-selective inhibitors were tested for dose-dependent inhibition, and IC₅₀ values were determined for each compound using the WST-1 assay. Results are the average of nine samples over three experimental trials.