In‐silico identification of high potential SSH‐2 specific inhibitors

Abstract

Cell growth and movement are controlled in part through the activation of a dual specificity phosphatase (DSP) called Slingshot‐2 (SSH‐2). SSH‐2 is known to contribute to the progression of cancer and Alzheimer's disease. For this reason, finding a specific inhibitor for SSH‐2 may have a profound impact in clinical treatments for different diseases. This study eliminates the need to manually test a very large chemical compound space by employing grid computer technologies in virtual molecular docking experiments to identify a list of high potential SSH‐2 inhibitors.Binding affinities were determined in the in‐silico experiments using a previously established grid‐computing workflow that uses the molecular docking simulation software, DOCK 6.0. The results from five DSP screenings, specifically SSH‐2, VHR, VH3, PTEN and KAP, suggest that 3‐[(4,5‐dimethoxy‐3‐oxo‐1H‐isobenzofuran‐1‐yl)amino]‐4‐methyl‐benzoic acid shows the highest affinity for SSH‐2, but lowest affinity for the other DSPs, among the best 100 SSH‐2 binding compounds. These results indicate that this compound has high specificity towards SSH‐2. Although these results must be confirmed through wet bench testing, this study eliminates compounds that are not likely to bind or show high specificity for SSH‐2 and provides a foundation for the analysis of molecular interactions of chemicals with SSH‐2.