Figure 6.

Compounds generated by expansion of the Z99 scaffold show improved efficacy in vitro and in cells. (A) Six new compounds were designed based on the Z99 scaffold. (B) Final poses of the scaffold expanded compounds docked into the EGC pocket of RAD52. Z99 is shown using surface representation, while the six new compounds are shown in stick representation. (C) IC₅₀ values for the disruption of the RAD52–ssDNA interaction (blue bars), of the RPA–ssDNA interaction (green), and of the RPA–ssDNA-RAD52 complex (grey). Error bars represent fitting errors. The inhibition curves for all compounds are shown in Supplementary Figure S5. (D) Cell viability was measured using CellTiter-Glo assay for five cell lines after 72 h treatment with 10 μM of indicated compounds. Hundred percent live cells corresponds to DMSO only control. The data are shown as average ± standard deviation for nine independent wells. The detailed statistical analysis for each compound is shown in Supplementary Figure S7.