Discovery of potent STAT3 inhibitors using structure-based virtual screening, molecular dynamic simulation, and
Weifeng Liu1, Zhijie Chu1, Cheng Yang1
1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China.
Introduction:
Signal transducer and activator of transcription 3 (STAT3) is ubiquitously hyper-activated in numerous cancers, rendering it an appealing target for therapeutic intervention.
Methods And Results:
In this study, using structure-based virtual screening complemented by molecular dynamics simulations, we identified ten potential STAT3 inhibitors. The simulations pinpointed compounds 8, 9, and 10 as forming distinct hydrogen bonds with the SH2 domain of STAT3. In vitro cytotoxicity assays highlighted compound 4 as a potent inhibitor of gastric cancer cell proliferation across MGC803, KATO III, and NCI-N87 cell lines. Further cellular assays substantiated the ability of compound 4 to attenuate IL-6-mediated STAT3 phosphorylation at Tyr475. Additionally, oxygen consumption rate assays corroborated compound 4's deleterious effects on mitochondrial function.
Discussion:
Collectively, our findings position compound 4 as a promising lead candidate warranting further exploration in the development of anti-gastric cancer therapeutics.
More Related Videos
10:29Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
08:49Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
