Disclosed herein are analogs of Salinosporamide A, having the Formulae
Ia-IVa as follows: ##STR00001## Like Salinosporamide A, the compounds of
the present invention will inhibit the proteasome, an intracellular
enzyme complex that destroys proteins the cell no longer needs. Without
the proteasome, proteins would build up and clog cellular machinery.
Fast-growing cancer cells make especially heavy use of the proteasome, so
thwarting its action is a compelling drug strategy.