Protein kinases are key regulators of cellular processes and critical therapeutic targets in diseases like cancer, making them a focal point for drug discovery efforts. In this context, we developed KinasePred, a robust computational workflow that combines machine learning and explainable artificial intelligence to predict the kinase activity of small molecules while providing detailed insights into the structural features driving ligand-target interactions. Our kinase-family predictive tool demonstrated significant performance, validated through virtual screening, where it successfully identified six kinase inhibitors. Target-focused operational models were subsequently developed to refine target-specific predictions, enabling the identification of molecular determinants of kinase selectivity. This integrated framework not only accelerates the screening and identification of kinase-targeting compounds but also supports broader applications in target identification, polypharmacology studies, and off-target effect analysis, providing a versatile tool for streamlining the drug discovery process.

KinasePred: A Computational Tool for Small-Molecule Kinase Target Prediction

Di Stefano, Miriana
Primo
;
Piazza, Lisa;Poles, Clarissa;Galati, Salvatore;Granchi, Carlotta;Macchia, Marco;Poli, Giulio
;
Tuccinardi, Tiziano
Ultimo
2025-01-01

Abstract

Protein kinases are key regulators of cellular processes and critical therapeutic targets in diseases like cancer, making them a focal point for drug discovery efforts. In this context, we developed KinasePred, a robust computational workflow that combines machine learning and explainable artificial intelligence to predict the kinase activity of small molecules while providing detailed insights into the structural features driving ligand-target interactions. Our kinase-family predictive tool demonstrated significant performance, validated through virtual screening, where it successfully identified six kinase inhibitors. Target-focused operational models were subsequently developed to refine target-specific predictions, enabling the identification of molecular determinants of kinase selectivity. This integrated framework not only accelerates the screening and identification of kinase-targeting compounds but also supports broader applications in target identification, polypharmacology studies, and off-target effect analysis, providing a versatile tool for streamlining the drug discovery process.
2025
Di Stefano, Miriana; Piazza, Lisa; Poles, Clarissa; Galati, Salvatore; Granchi, Carlotta; Giordano, Antonio; Campisi, Luca; Macchia, Marco; Poli, Giul...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1314311
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