Calpain inhibitor I is a synthetic tripeptide aldehyde that acts as a potent inhibitor of cysteine proteases including calpain I (Ki = 190 nM), calpain II (Ki = 220 nM), cathepsin B (Ki = 150 nM), and cathepsin L (Ki = 500 pM). At 10-100 μM calpain inhibitor I dose-dependently prevents the degradation of IκBα and IκBβ by the ubiquitin-proteasome complex, which blocks activation of NFκB and the production of TNF and IL-1β, suggesting a potential therapeutic effect for inflammatory diseases. At 10 μM, calpain inhibitor I can inhibit nitric oxide production by activated macrophages by interfering with transcription of the inducible nitric oxide synthase gene.
