**5.1.4 Epoxyketones**

These are naturally product proteasome inhibitors isolated from actinomycete fermentation broths by screening for antitumor activity in mice. Examples of this class include Epoxomicin and eponemycin. These compounds inhibit the chymotrypsin like site only or the chymotrypsinlike and caspaselike, respectively. In contrast to previously mentioned inhibitors, epoxomicin initially forms a covalent bond between the proteasome's aminoterminal threonine hydroxyl at its C-terminal ketone carbonyl. This primary adduct formation is followed by formation of a stable six-membered ring adduct by a second attack by the terminal free amino group [Groll et al., 2000].
