USP14 and cancer: Genetic profiling has linked USP14 overexpression to many important diseases.24,25 Knockout of USP14 has shown beneficial phenotypes, indicating that USP14 is a potential drug target for cancer therapy.18,25–35 As tool compounds, IU1 and IU1-47 have been employed in interesting cell-based studies.25,32,36–38 However, the relatively weak activity (IC50, i.e., μM) of the IU-series compounds has to be improved for the purpose of proof-of-concept studies.