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IU1 is a **small molecule, reversible and selective inhibitor of the deubiquitinating enzyme USP14** (ubiquitin-specific protease 14), a proteasome-associated DUB. By inhibiting USP14, IU1 enhances the proteasome-dependent degradation of ubiquitin-protein conjugates, increases global protein turnover, and induces autophagy. IU1 has demonstrated capacity to decrease pathologic protein accumulation, induce cell cycle arrest, and promote apoptosis in cancer cell models. Its mechanism involves stabilizing protein homeostasis via both the ubiquitin-proteasome system (UPS) and autophagy. IU1 has mainly been used as a research tool and in experimental models for neurodegenerative diseases (such as Alzheimer's and Parkinson's) and for cancer cell regulation. However, it can show off-target toxicity (including neurotoxicity and mitochondrial dysfunction at higher concentrations), especially by inhibiting mitochondrial Complex I activity and impacting cellular ATP levels[1][2][5][6][7][8][9].
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