Open AccessOxathiazolones Selectively Inhibit the Human Immunoproteasome over the Constitutive Proteasome
Author(s) -
Hao Fan,
Nicholas G. Angelo,
Joel Warren,
Carl Nathan,
Gang Lin
Publication year - 2014
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml400531d
Subject(s) - proteasome , protein subunit , cell , chemistry , microbiology and biotechnology , proteasome inhibitor , biology , biochemistry , gene
Selective inhibitors for the human immunoproteasome LMP7 (β5i) 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 β5i with up to 4700-fold selectivity over the constitutive proteasome, are cell permeable, and inhibit proteasomes inside cells.