Identification of Small Molecule Inhibitors of PTPσ through an Integrative Virtual and Biochemical Approach
Figure 1
Workflow overview for PTPσ inhibitor development.
In silico docking was performed using the crystal structure of the D1 active site of PTPσ as a target (PDB ID: 2fh7). Three structurally distinct scaffolds were chosen, along with 74 additional compounds identified by a sub-structure search of compounds in the ChemBridge, were tested in vitro to for the ability to inhibit PTPσ phosphatase activity. To eliminate oxidation-mediated inhibition, we optimized the biochemical assay and discovered one lead compound whose inhibition was not mediated by oxidation. Future efforts (dashed boxes and lines) will introduce selectivity into this lead compound through a detailed structural analysis of PTPσ and related PTPs.