In-silico target prediction by ensemble chemogenomic model based on multi-scale information of chemical structures and protein sequences.

Identification and validation of bioactive small-molecule targets is a significant challenge in drug discovery. In recent years, various in-silico approaches have been proposed to expedite time- and resource-consuming experiments for target detection. Herein, we developed several chemogenomic models for target prediction based on multi-scale information of chemical structures and protein sequences.

Minor structural modifications to Pracinostat produce big changes in its biological responses.

A series of compounds similar to Pracinostat that contained benzimidazole ring and N-hydroxyacrylamide attached at 5- or 6-position were designed, synthesized, and evaluated as HDAC inhibitors. It was interesting to find that the corresponding derivative 1 with N-hydroxyacrylamide attached at 5-position was a potent HDAC inhibitor while the others at 6-position were not. This is the first time to demonstrate the position difference plays important role in the HDAC inhibitory activities of the cinnamic hydroxamates.