Discovery of novel PRL-3 inhibitors based on the structure-based virtual screening

The inhibitors of phosphatase of regenerating liver-3 (PRL-3) have been shown to be useful as therapeutics for the treatment of cancer. We have been able to identify 12 novel PRL-3 inhibitors by means of the virtual screening with docking simulations under the consideration of the effects of ligand solvation in the scoring function. Because the newly identified inhibitors are structurally diverse and reveal a significant potency with IC50 values ranging from 10 to 50 μM, all of them can be considered for further development by structure–activity relationship or de novo design methods. Structural features relevant to the interactions of the newly identified inhibitors with the amino acid residues in the active site and the peripheral binding site of PRL-3 are discussed in detail.

Graphical abstractWe have discovered 12 novel PRL-3 inhibitors by means of a computer-aided drug design protocol involving homology modeling of the target protein and the virtual screening with docking simulations.Figure optionsDownload full-size imageDownload as PowerPoint slide