314245-33-5

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.

IU1 has been used for the inhibition of Ubiquitin Specific Peptidase 14 (USP14) in human neuroblastoma cells (SH-SY5Y) and in ubiquitin-rhodamine hydrolysis plate assay.

IU1 is an inhibitor of USP14, a deubiquitinating enzyme associated with the proteasome. The proteasome mediates the cellular degradation of oxidized, damaged and misfolded proteins which, if not removed, accumulate and become toxic to cells. Proteins targeted for proteasomal degradation are first ubiquitinated, with longer length ubiquitin chains interacting more strongly with the proteasome. Deubiquitinating enzymes (DUBs) such as USP14 interfere with the degradation process. IU1 inhibits USP14-mediated ubiquitin "chain-trimming" thereby enhancing substrate degradation by the proteasome. The compound may help to eliminate toxic proteins more effectively by enhancing their degradation.

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]