SENPs are attractive drug candidates due to their involvement with various diseases, especially cancers. Although several inhibitors are currently available for SENPs, they lack potency and selectivity, hampering the biological research of SENPs. Therefore, one of the main objectives of this thesis is to develop more selective and potent inhibitors for SENPs to investigate the function of SENPs in a cellular context and explore new therapeutics.
PARK7 is a small multifunctional protein that regulates a broad of cellular events, and it is well-known that dysregulation of PARK7 is related to various diseases, e.g. Parkinson’s disease, and cancer. Although it has been extensively studied for over two decades, a dedicated chemical toolbox for PARK7 is still missing, such as potent and well-characterized inhibitors, activity-based probes, and assay reagents. Thus, another main objective of the thesis is to develop such kind of chemical tools to advance the understanding of PARK7 and explore the therapeutic possibilities for cancer and neurodegenerative diseases.