2018年10月23日（周二） 2:30-3:30 p.m.
The proteasome is the primary proteolytic machine for breaking down cytosolic and nuclear proteins in eukaryotes. It is essential for multiple cellular processes including protein quality control, regulation of gene expression, and cell cycle progression, and therefore has become an important target for anticancer therapy. Proteasome activity is also closely related to aging and neurodegenerative diseases, as misfolded protein compromise the function of proteasome and impair the protein homeostasis. FDA approved ‘omib’ drugs such as bortezomib and carfilzomib inhibit the active sites in the 20S proteasome core particle. They are important therapeutic agents for the treatment of multiple myeloma. However, despite the clinical benefit that they provide, patients ultimately relapse, and new agents are urgently needed. We discovered capzimin, a first-in-class selective inhibitor targeting Rpn11, an essential subunit located on the 19S proteasome regulatory particle. It stabilized proteasome substrates, induced an unfolded protein response, and blocked proliferation of cancer cells, including those resistant to bortezomib.
Jing Li received Bachelor of Medicine in Peking University Health Science Center and Ph.D. in Biochemistry from Technical University of Munich, where he finished his graduate research at the International Max-Planck Research School for Life Science and graduated summa cum laude. He is currently a post-doctoral scholar in the oncology division at the Amgen Inc. His research focused on understanding the mechanism of protein homeostasis network and exploiting its potential in the treatment of human diseases such as cancer and neurodegenerative diseases. He has co-authored 13 manuscripts and one patent in the areas of protein folding, protein degradation, and early drug discovery research.