Abstract：Objective To discover small molecule inhibitors of protein tyrosine phosphatase Shp2 (PTP-Shp2). Methods We used a high-throughput screening method to find small molecular inhibitors of PTP-Shp2 and kinetic analysis of Shp2 inhibition was implemented. We assessed the inhibitor binding sites in Shp2 using molecular docking. Results In this study, flavoglaucin was identified as a Shp2 inhibitor from products of microbial metabolism in our lab by a high-throughput screening method with an IC50 value of 5.08μmol/L. The lineweaver-burk analysis suggested that flavoglaucin was a non-competitive inhibitor of Shp2. Molecular docking of flavoglaucin with Shp2 showed that flavoglaucin formed three hydrogen bonds with the WDP loop of Shp2. Conclusion Flavoglaucin which is from products of microbial metabolism is a novel inhibitor of Shp2.
