https://www.selleckchem.com/products/nik-smi1.html Inflammatory bowel disease is a chronic and pathologic autoimmune condition. And immunoproteasome is becoming an attractive therapeutic target for autoimmune inflammatory diseases. In this study, we evaluated the therapeutic effects of a specific small molecule inhibitor of the chymotryptic-like β5i subunits of the immunoproteasome, DPLG3, in a preclinical murine colitis model and explored the underlying molecular mechanism for the immune suppression. DPLG3 showed significant effects in attenuating the disease progression in experimental colitis, reducing the body and spleen weight losses, and colon length shortening compared to vehicle-treated controls and to the well studied immunoproteasome inhibitor ONX-0914. Mechanistically, DPLG3 decreased inflammatory cytokines and the influx of effector T cells and macrophages in colon tissues while increasing the number of regulatory T cells. Molecular docking analysis of the protein-ligand interaction profile revealed that the β5i-DPLG3 complex was more stable and efficient in the binding sites compared to those formed with ONX-0914 and LU-005i. Furthermore, DPLG3 reduced the protein levels of the canonical NF-κB p50 and p65, as well as the nuclear p65. Thus, DPLG3 constitutes a potentially efficacious clinical agent for autoimmune inflammatory diseases. Eosinophils are a type of granulated innate immune cells that have long been implicated in a specific type of asthma, referred to as eosinophilic asthma. Several immunotherapeutics that target and deplete eosinophils or limit their numbers are currently widely used and provide improved disease outcome in severe eosinophilic asthma. Current clinical results provide conclusive evidence of a generally detrimental role of eosinophils in asthma. Yet, a small but growing body of reports suggests that eosinophils may be more diverse than currently appreciated. In this review, we explore pre-clinical and clinical evidence that sug