I-14

I-14 is a potent and selective small molecule inhibitor of the deubiquitinating enzyme (DUB) ubiquitin-specific protease 14 (USP14). USP14 is a proteasome-associated DUB that regulates protein degradation by removing ubiquitin chains from substrates before they are processed by the 26S proteasome. By inhibiting USP14, I-14 enhances the degradation of specific proteasome substrates, including misfolded or pathogenic proteins such as tau and TDP-43, which are implicated in neurodegenerative diseases. In oncology, I-14 has demonstrated the ability to inhibit tumor cell proliferation and induce apoptosis by disrupting protein homeostasis and promoting the degradation of oncogenic proteins. It is primarily utilized as a chemical probe in preclinical research to investigate proteasome regulation and as a potential lead compound for treating proteinopathies and various cancers.