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2 Interfaculty Institute for Biomedical Informatics (IBMI), Eberhard Karls Universitt Tbingen, Tbingen, 72076, Germany Correspondence: Frank M Boeckler, Department of Pharmacy and Biochemistry, Laboratory for Molecular Design & Pharmaceutical Biophysics, Eberhard Karls Universitt Tbingen, Institute of Pharmaceutical Sciences, Tbingen, 72076, Germany, Tel +49 7071 29 74567, Email [email protected] Purpose: Covalent Fragment-Based Drug Discovery (FBDD) has emerged as a powerful strategy for unlocking challenging pharmacological targets and engaging shallow or cryptic binding pockets

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the dominance of preclinical studies raises concerns about translational validity, as mouse models cannot fully replicate human conditions