High-resolution snapshots of proteasome inhibitors in action revise inhibition paradigms and inspire next-generation inhibitor design

Abstract

The proteasome, which mediates the ubiquitin-dependent degradation of intracellular proteins, is well recognized as an important anticancer target (Figure 1). So far, three inhibitors of this multiprotease complex have received FDA approval for treating multiple myeloma: the peptide boronic acids bortezomib and ixazomib and the peptide epoxyketone carfilzomib.([1]) Several other proteasome inhibitors have entered clinical trials, including the peptide boronic acid delanzomib and the peptide epoxyketone oprozomib.([2]) [GRAPHICS] .