Signal transducer and activator of transcription 3 is a latent transcription factor involved in various cellular processes, cell proliferation, apoptosis, inflammation, immunity, angiogenesis, and metastasis. Controlled regulation of STAT3 activity is maintained in normal cells, but its sustained activation causes tumor growth and carcinogenesis. This computational study aims to elucidate the potential of FDA-approved non-steroidal anti-inflammatory drugs in inhibiting STAT3. Molecular Docking was performed using AutoDock and visualized through LigPlot+ and Biovia Discovery Studio Visualizer. The findings demonstrate that NSAIDs, including ibuprofen, naproxen, diclofenac, celecoxib, mefenamic acid, etoricoxib, indomethacin, and aspirin, exhibit substantial binding affinity with STAT3 monomers. The binding energies calculated are -5.6 to 7.5 kcal/mol, with inhibition constants from 7.5 to 3.03µM, respectively. Notably, key amino acid residues such as GLN326, HIS457, LYS244, PRO487, ARG335, ASP566, CYS468, PRO471, LYS383, LEU378, VAL323, THR456, LYS318, GLU455, ASP570, LYS573, CYS251, TRP474, PRO336, ASP334, SER403, ILE258, ARG325, LYS348, ARG350, and GLU324 are identified as pivotal in mediating the interaction between NSAIDs and STAT3. This study provides valuable insights into the molecular interactions between FDA-approved NSAIDs and STAT3, offering a foundation for further exploration of their potential as therapeutic agents in the context of STAT3-mediated diseases.
Key words: FDA-approved drugs, Molecular docking, NSAIDs, STAT3, Anticancer, Drug discovery