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IU1 is a selective USP14 inhibitor. IU1 prevents ventilator-induced lung injury in rats. IU1 inhibits the catalytic activity of proteasome-associated Usp14 in vitro (IC50 < 4 μM). IU1 stimulates proteasome activity and substrate degradation. USP14 removes the ubiquitin chain of I-κB, therefore inducing I-κB degradation and increasing cytokine release.