Disclosed herein are analogs of Salinosporamide A, having the Formulae
Ia-IVa as follows: 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.