Virtual Screening And Preliminary Biological Activity Evaluation For Small Molecule Inhibitors Of STAT3 Based On Three-dimensional Structure

Background: The signal transducer and activator of transcription 3 is the hub of many carcinogenic signal pathway,such as EGFR pathway,IL-6/JAK pathway,Src pathway and so on.Stat3 is recently considered to be a hot target of the antineoplastic drug,but the discovered STAT3 inhibitors are either low activity or poor selective,and cannot efficiently pass through the cell membrane.This study planned to virtual screen for small molecule inhibitors of STAT3 based on the three-dimensional structure and preliminarily evaluate the biological activity of inhibitors.Objective: To discover novel small molecule inhibitors of STAT3 by structure-based virtual screening,and then preliminarily evaluate the biological activities of STAT3 inhibitors.Materials: In this study,the small molecule database was screened by Glide of Schrodinger Suite 2009.The candidates were manually picked out by docking score and analyzing the interaction of receptor and ligand.The preliminary biological activities of the candidates were evaluated by fluorescence polarization assay.Results: According to docking score and analyzing the interaction of receptor and ligand,a series of small molecules were predicted to have good interaction with STAT3.Among them,11 small molecules were selected for biological activity detection.One compound possessed inhibitive activity,others showed no or weak activity.Conclusion: One compound with inhibitive activity was discovered.It is expected that the small molecule inhibitor of STAT3 identified at present study could be helpful for the discovery of new lead compound of novel small molecule inhibitor.