Computational identification of anti-cancer compounds targeting the RNA-binding domain of human FOX-1 protein (RBFOX1)

• RBFOX1 is upregulated in cancers, promoting proliferation, progression, and metastasis. • Novel inhibitors targeting RBFOX1 pathways were investigated. • Docking showed strong binding affinities for selected compounds. • MD simulations confirmed complex stability via RMSD and RMSF analyses. • Key interactions showed hydrogen bonds with active residues, suggesting therapeutic potential. The transcription factor RBFOX1 is essential for cellular proliferation and has shown upregulation in many human cancers. The overexpression of this gene correlates with the motility of cancer cells, their ability to invade surrounding tissues. The aforementioned processes are pivotal in cancer progression, making RBFOX1 a significant target for innovative cancer therapies. The present study seeks to identify new inhibitor compounds that obstruct the biological processes of the target protein associated with cancer. Results shows that control (3S,5aS,6R,8aS,9R,10S,12R,12aS)-3,6,9-trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromen-10-ol (artenimol) reflecting the binding affinities of −7.9 kcal/mol, Top1 (4-[[2-butyl-5-[(E)-2-carboxy-3-thiophen-2-ylprop-1-enyl]imidazol-1-yl]methyl]benzoic acid) shows −8.7 kcal/mol and Top2 (R)-1-carboxy-5-((S)-2-((2R,4S)-4-carboxy-5,5-dimethylthiazolidin-2-yl)-2-(2-phenylacetamido)acetamido)pentan-1-aminium indicating −8.2 k cal/mol. Additional, molecular dynamic simulation studies shows significant stability during RMSD and RMSF analyses over a 100 ns timescale. Binding domain residues i.e. Phe52, Arg10, Thr84, Ala85 and Arg86 has demonstrated the stability of the system due to robust hydrogen bonds. All of the top hit inhibitor exhibited more stability in comparison to the control inhibitor, where it penetrated deeply, as depicted in PCA analysis. Binding energies and Waterswap calculations significantly refines our comprehensive simulation model. Consequently, our findings provide a potential framework for researchers to further explore in vivo and in vitro analyses of inhibitors targeting the HBFOX1 gene, representing a potential advancement in cancer treatment.