bortezomib and ixazomib

The immunoproteasome, a specialized form of proteasome, is mainly expressed in lymphocytes and monocytes of jawed vertebrates and responsible for the generation of antigenic peptides for cell-mediated immunity. Overexpression of immunoproteasome have been detected in a wide range of diseases including malignancies, autoimmune and inflammatory diseases. Following the successful approval of constitutive proteasome inhibitors bortezomib, carfilzomib and Ixazomib, and with the clarification of immunoproteasome crystal structure and functions, a variety of immunoproteasome inhibitors were discovered or rationally developed. Not only the inhibitory activities, the selectivities for immunoproteasome over constitutive proteasome are essential for the clinical potential of these analogues, which has been validated by the clinical evaluation of immunoproteasome-selective inhibitor KZR-616 for the treatment of systemic lupus erythematosus. In this review, structure, function as well as the current developments of various inhibitors against immunoproteasome are going to be summarized, which help to fully understand the target for drug discovery.

Topics: Animals; Antineoplastic Agents; Autoimmune Diseases; Boron Compounds; Bortezomib; Glycine; Hematologic Neoplasms; Humans; Oligopeptides; Proteasome Endopeptidase Complex; Proteasome Inhibitors

Caseinolytic protease P (ClpP) is considered as a promising target for the treatment of

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Boron Compounds; Boronic Acids; Endopeptidase Clp; Female; Glycine; Humans; Methicillin-Resistant Staphylococcus aureus; Mice, Inbred BALB C; Molecular Docking Simulation; Molecular Structure; Peptidomimetics; Protein Binding; Serine Proteinase Inhibitors; Skin; Small Molecule Libraries; Staphylococcal Skin Infections; Structure-Activity Relationship; Virulence