Identification of Small Molecule Inhibitors of PTPσ through an Integrative Virtual and Biochemical Approach
Figure 6
Compound 36 is a µM inhibitor of PTPσ and binds the PTPσ active site in silico.
(A) Compound 36 was tested for inhibition of PTPσ. Compound 36 (at a final concentration from 0 to 100 µM) was pre-incubated with PTPσ for 10 min at 37°C. Reactions were then performed for 10 minutes at 37°C following the addition of 225 µM pNPP substrate. Relative PTPσ activity is plotted (percent of activity in DMSO). Dashed line indicates 50% inhibition (10 µM). Bars represent standard deviation from three experiments. (B) The structure of compound 36 is displayed. (C) Compound 36 was docked into the active site of PTPσ (PDB ID: 2FH7) using the D1 apo crystal structure. Molecular surface is colored by electrostatic potential. Red corresponds to negative potential and blue to positive potential. Docking was performed using the Schrödinger suite of software as described in Methods and figures generated using ICM (MolSoft).