Fig. 4: Library enrichment to identify Snail1 inhibitors.
From: Bioactivity descriptors for uncharacterized chemical compounds
a Scheme of the methodology. Two compound libraries are screened (IRB and PWCK). A chemical query is done by looking for similarities with known DUB inhibitors. A biological query is done by looking for transcriptional (D1) and network-based (C3–5) signature matchings with Snail1-relevant targets. Random molecules are selected to estimate the background hit-rate. A Snail1 expression assay based on Firefly:Renilla luciferase ratios are used to screen candidate compounds. b Library enrichment quantification showing the effects of compounds selected by chemical (red), biological (blue), shared between both (magenta), and random (gray) queries, as well as the positive (PR-619) and negative (DMSO) controls. c Detail of the top 25 hit compounds. d Fold enrichment of compounds selected by chemical (red), biological (blue), and shared (magenta) queries with respect to random picks, based on their capacity to modulate Snail1 levels (Firefly:Renilla assay). Median ± MAD (n = 4). e MDA-MB-231 cells stably expressing luciferase constructs were treated for 6 h with the indicated compounds, at different doses. Firefly:Renilla ratios were normalized with the corresponding concentration of vehicle (DMSO). Mean ± SD of 2 independent experiments, each of them including 4 replicas, are shown.
