Table 1.

Some proteasome antagonists and their characteristics.

Inhibitor	Properties	Proteasomal Binding and Targeted Activities	Other Cellular Effects
Bortezomib	First-class; FDA-approved (Velcade®) for first-line treatment of multiple myeloma	Reversibly binds 26S proteasome and immunoproteasome; chymotrypsin -> caspase -> trypsin-like activity	NF-κB inhibition; cell apoptosis due to accumulation of proteins, stress induction, and disruption of cell cycle
Carfilzomib	New generation; FDA-approved (Kyprolis®) against relapsing multiple myeloma; less toxic than Bortezomib	Irreversibly binds 20S proteasome and immunoproteasome; chymotrypsin-like activity	Cell apoptosis
Lactacystin	Isolated from soil Actinomycetes; Prodrug, metabolized into a β-lactone (Omuralide) in vivo; inhibits non-proteasome proteases like cathepsin	Irreversibly binds 20S proteasome and immunoproteasome; all activities, with preference to chymotrypsin-like activity	Inhibits cellular growth; cell apoptosis; NF-κB downregulation
Epoxomicin	Isolated from Actinomycetes strain; specific	Irreversible binds 20S proteasome; all activities, with preference to chymotrypsin-like activity	Inhibits NF-κB signaling
MG132	Peptide aldehyde isolated from Chinese medicinal herbs; first choice to study UPS in human cell lines	Irreversibly binds 20S proteasome; all activities, with preference to chymotrypsin-like activity	Cell cycle arrest and apoptosis; inhibits NF-κB activation