Journal: Cells

Article Title: A Nut for Every Bolt: Subunit-Selective Inhibitors of the Immunoproteasome and Their Therapeutic Potential

doi: 10.3390/cells10081929

Figure Lengend Snippet: Overview of iCP selective inhibitors and their potency. Due to space limitations, only key compounds of each class are presented. IC 50 values (given in [µM]) depend on the chosen setting (purified CP/cell lysate/in cells), enzyme concentration and time of incubation, and thus are hardly comparable. As a measure of subunit selectivity, ratios of IC 50 values are given. The ratio positively correlates with selectivity for the respective i-subunit. ‘n.r.’ designates values that have not been reported. Colors reflect the distinct selectivity patterns of inhibitors: green for β1i-, brown for β2i-, yellow for β5i- and gray for pan-reactive inhibitors. Inhibition values are light-colored, while selectivity ratios are dark-shaded. Most pan-reactive inhibitors target β1i and β5i (green and yellow shades, respectively). Only LU-005i moderately inhibits all immunoproteasome subunits (green, brown and yellow shades).

Article Snippet: Only recently, Kezar Life Sciences Inc. reported another β5i-selective inhibitor (compound 8 ( , ); IC 50 values determined in MOLT-4 cell lysates: 0.034 μM for β5i; 78-fold selectivity for β5i over β5c) [ ].

Techniques: Purification, Concentration Assay, Incubation, Inhibition