Figure 2.

Virtual screening protocol utilized for the evaluation of the NCI/DTP Repository. Compounds were subjected to three different in silico screening methodologies. Two-dimensional similarity (toward 1, Canvas software, left-side funnel) was performed after discarding benzodiazepine-containing structures (BZDs). The top 2% diverse NCI/DTP molecules were additionally docked to the BRD (Glide software, middle funnel). In parallel, three-dimensional similarity was undertaken for the total collection (toward 1, ROCS software, right-side funnel). Finally, rank-ordered results originating from each of the three distinct filters were combined by a consensus ranking approach and the top 40 compounds were assayed experimentally for their BRD-binding affinity.