epoxomicin

Epoxomicin is a potent, naturally occurring epoxyketone tetrapeptide that acts as a highly selective and irreversible inhibitor of the 20S proteasome. Originally isolated from *Actinomadura* species, it distinguishes itself from other proteasome inhibitors by its unique mechanism of action, where the epoxyketone moiety forms a dual covalent bond with the N-terminal threonine of the proteasome's catalytic subunits, creating a stable morpholino ring. This specificity prevents the off-target inhibition of non-proteasomal proteases such as calpains and cathepsins, which is common with peptide boronate or aldehyde inhibitors. While epoxomicin itself is primarily utilized as a high-precision research tool in cell biology and oncology to study protein degradation and apoptosis, it served as the structural lead for the development of the second-generation proteasome inhibitor carfilzomib.

Other names

Epoxomicin