IU1 (314245-33-5) is a selective inhibitor of Usp14 (IC50<4 μM). Enhances proteasome activity and substrate proteolysis.1,2 Inhibits Dengue virus replication.3 In prion-infected CAD5 cells activation of the ubiquitin proteasome system by IU1 is sufficient to induce clearance of polyubiquitinated substrates and reduce misfolded prion protein load.4 Attenuates ischemia/reperfusion-induced neuronal injury in a mouse model.5 Cell permeable.
1) Lee et al. (2010), Enhancement of proteasome activity by a small-molecule inhibitor of USP14; Nature, 467 1179
2) Lee et al. (2010), Trimming of ubiquitin chains by proteasome-associated deubiquitinating enzymes; Mol. Cell. Proteomics, 10 R110
3) Nag and Finley (2012), A small-molecule inhibitor of deubiquitinating enzyme USP14 inhibits Dengue virus replication; Virus Res., 165 103
4) McKinnon et al. (2016), Prion-mediated neurodegeneration is associated with early impairment of the ubiquitin-proteasome system; Acta Neuropathol., 131 411
5) Min et al. (2017), USP14 inhibitor attenuates cerebral ischemia/reperfusion-induced neuronal injury in mice; J. Neurochem., 140 826
6) Homma et al. (2015); Ubiquitin-specific protease 14 modulates degradation of cellular prion protein; Sci. Rep. 5 11028 [FOCUS CITATION]