Table 2.
Hits from Z99 scaffold expansion
| Compound | Inhibition of the RAD52–ssDNA interaction, IC50 (μM) | Inhibition of the RPA–ssDNA interaction, IC50 (μM) | Inhibition of the RPA–ssDNA–RAD52 complex, IC50 (μM) | Toxicity towards BRCA-deficient cells (at 10 μM) | Toxicity towards BRCA-proficient cells (at 10 μM) |
|---|---|---|---|---|---|
| Z5862216254 | 7.26 ± 0.61 | 18.0 ± 1.3 | N/A | yes (EUFA423F, Capan1, MDA-MB-436) | no |
| Z5862231762 | 2.84 ± 0.32 | 28.8 ± 4.0 | 4.55 ± 0.16 | yes/no (Capan1, MDA-MB-436) | no |
| Z5862148469 | 2.02 ± 0.12 | 1.12 ± 0.13 | 0.76 ± 0.05 | yes/no (Capan1, MDA-MB-436) | no |
| Z5862209772 | 7.97 ± 0.84 | 15.9 ± 1.4 | 7.00 ± 0.29 | yes (EUFA423F, Capan1, MDA-MB-436) | no/yes (MCF10a in colony formation assay) |
| Z5862135983 | 6.21 ± 0.42 | 54.0 ± 9.7 | 54.3 ± 16.2 | yes (EUFA423F, Capan1, MDA-MB-436) | no/yes (MCF10a in colony formation assay) |
| Z5862219887 | 3.98 ± 0.35 | 8.49 ± 1.43 | 6.43 ± 1.01 | yes (EUFA423F, Capan1, MDA-MB-436) | no |
N/A – no activity