E-64 #90267

The small-molecule E-64 is an anti-parasitic and anti-malarial agent that acts as an irreversible, non-selective inhibitor of cysteine proteases. E-64 binds and inhibits the cysteine proteases cathepsin K (IC₅₀ = 1.4 nM), cathepsin S (IC₅₀ = 4.1 nM), and cathepsin L (IC₅₀ = 2.5 nM) in human osteoclast assays. E-64 also inhibits other proteases, including cathepsin B, cathepsin H, papain, and calpain (1,2). Exposure of filarial parasites to E-64 inhibited cathepsin B and resulted in decreased parasite motility and viability (3). E-64 effectively inhibited a SUMO-1-like cysteine protease from the African swine fever virus, resulting in impaired viral replication and a possible treatment for a viral disease that typically causes high mortality in domestic pigs (4). Inhibition of cathepsin B by E-64 in tumor cell lines reduced the invasive properties of the cells by 75% (5). E-64 treatment of ischemia-reperfusion rat kidneys blocked calpain activity and reduced several markers of renal dysfunction (6).