The proteasome is a multi-enzyme complex involved in
the ubiquitin-proteasome pathway control of cell-cycle
progression, in the termination of signal transduction cascades,
and in the removal of mutant, damaged, and misfolded
proteins. As such, it is a promising therapeutic target, and
the background to this aspect has been reviewed. The
synthetic dipeptidyl peptide boronate, bortezomib (Velcade)
(112; Scheme 20), is the first clinical drug that uses this
MOA, and the development of this compound, which is based upon a natural product-based structure that inhibited
chymotrypsin, has been described by the original inventor