Janus kinases (JAKs) and their gain-of-function mutants have been implicated in a range of oncological, inflammatory, and autoimmune conditions, which has sparked great research interest in the discovery and development of small-molecule JAK inhibitors. Two molecules are currently marketed as JAK inhibitors, but due to the displayed side effects (owing to their suboptimal selectivities among the various JAK subtypes) new JAK inhibitors are still sought after. We present the results of an extensive virtual screening campaign based on a multi-step screening protocol involving ligand docking. The screening yielded five new, experimentally validated inhibitors of JAK1 with 8-hydroxyquinoline as a novel hinge-binding scaffold. The compounds did not only display favorable potencies in a JAK1(V658F)-driven cell-based assay but were also shown to be non-cytotoxic on rat liver cells.