Oxathiazolones Selectively Inhibit the Human Immunoproteasome over the Constitutive Proteasome

Selective inhibitors for the human immunoproteasome LMP7 (beta 5i subunit over the constitutive proteasome hold promise for the treatment of autoimmune and inflammatory diseases and hematologic malignancies. Here we report that oxathiazolones inhibit the immunoproteasome beta 5i with up to 4700-fold selectivity over the constitutive proteasome, are cell permeable, and inhibit proteasomes inside cells.