Figure 1 | Scientific Reports

Figure 1

From: Discovering cell-active BCL6 inhibitors: effectively combining biochemical HTS with multiple biophysical techniques, X-ray crystallography and cell-based assays

Figure 1

Summary of HTS campaign and hit validation by orthogonal biophysical techniques. An HTS was carried out using an FP assay with an FP-probe based on a BCOR corepressor peptide. The primary HTS hits were subjected to a first confirmation step at three concentrations in the FP assay. Hits confirmed in this step were progressed to IC50 determination in the FP assay using repurchased material. Active hits were characterised in orthogonal biophysical techniques including TSA, SPR and LO-NMR using a 19F-labelled WVIP reporter peptide. Compound selection for the respective biophysical assays was heavily based on experimental aqueous solubility experiments on the confirmed hits using NMR and HPLC. Hits confirmed to bind the BCL6-BTB ___domain in one or more biophysical methods were selected for binding mode elucidation by X-ray crystallography which yielded 12 protein–ligand structures representing 9 different chemical series.

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