Novel β-lactam derivatives: Potent and selective inhibitors of the chymotrypsin-like activity of the human 20S proteasome

A series of β-lactam derivatives has been designed and synthesized to inhibit the chymotrypsin-like activity of the human 20S proteasome. The most potent compounds of this new structural class of β-subunit selective 20S proteasome inhibitors exhibit IC 50 values in the low-nanomolar range and show good selectivity over the trypsin-like and post-glutamyl-peptide hydrolytic activities of the enzyme.