Identification of Small Molecule Inhibitors of PTPs through an Integrative Virtual and Biochemical Approach

This research focuses on finding molecules that can block the activity of an enzyme called PTPs, which is important in nerve regeneration and cancer cell survival. Blocking PTPs could potentially help treat spinal cord injuries and diseases where increasing autophagy is beneficial. The researchers used computer modeling to find compounds that might bind to PTPs, then tested these compounds in the lab to see if they actually inhibited the enzyme. They found that some compounds seemed to work by creating oxidative species, which isn't ideal. After optimizing their testing methods to avoid this oxidation issue, they identified a compound that directly inhibits PTPs. This compound could be a starting point for developing more selective drugs that target PTPs.

• 1
  Several compounds were identified that inhibit PTPs activity in vitro with micromolar potency.
• 2
  Many active compounds inhibited PTPs by generating oxidative species, which is a non-selective mechanism.
• 3
  Compound 36 was identified as a lead compound that inhibits PTPs in a primarily oxidation-independent manner with an IC50 of 10 mM and favorably binds the D1 active site of PTPs.