RESUMO
The 26S proteasome is a 2.5 MDa complex of the protease family members and is central to a vast array of vital cellular processes including cell-cycle progression and antigen presentation. It has been proven to be a target for therapeutic agents in the treatment of cancers and autoimmune diseases. Most inhibitors are designed to target the 20S proteolytic core complex while the efforts to target the 19S regulatory particle subunits are less successful so far. This is, in part, due to the complexity of molecular architecture and poor understanding of the mechanism of this subcomplex. This review attempts to summarize the development of inhibitory molecules that target both the 20S and 19S subunits of the proteasome, especially highlight the recent progress in the proteasome structure and development of the new inhibitors.