The use of computational and experimental approaches in this study allowed for the identification and characterization of previously unknown off-target interactions for the two JAK inhibitors (e.g., baricitinib-PDE10A and tofacitinib-TRPM6), which adds to the known literature on the potential drug-effects of these drugs. Moreover, the reference annotated targets used by the computational methods(72) encompasses a broad scope of protein families, which may allow identification of drug promiscuity and predict a broad off-target drug profile, pointing out potential targets for repurposing studies.