IU1-47 is an inhibitor of ubiquitin-specific protease 14 (USP14; IC50 = 0.6 ?M).1 It is selective for USP14 over USP5 (IC50 = 20 ?M). IU1-47 increases degradation of a ubiquitinated proteasome substrate in a cell-free assay. It reduces tau levels in wild-type mouse embryonic fibroblasts (MEFs) expressing human tau but not Usp14-null MEFs expressing human tau. IU1-47 (25 ?M) reduces tau levels in primary rat cortical neurons. It also decreases migration of, and increases autophagy in, A549 and H1299 cancer cells.2
1.Boselli, M., Lee, B.-H., Robert, J., et al.An inhibitor of the proteasomal deubiquitinating enzyme USP14 induces tau elimination in cultured neuronsJ. Biol. Chem.292(47)19209-19225(2017) 2.Han, K.H., Kwak, M., Lee, T.H., et al.USP14 inhibition regulates tumorigenesis by inducing autophagy in lung cancer in vitroInt. J. Mol. Sci.20(21)5300(2019)