Novel beta-lactam derivatives: potent and selective inhibitors of the chymotrypsin-like activity of the human 20S proteasome.
A series of beta-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 beta-subunit selective 20S proteasome inhibitors exhibit IC50 values in the low-nanomolar range and show good selectivity over the trypsin-like and post-glutamyl-peptide hydrolytic activities of the enzyme.
Imbach
Patricia
P
Novartis Institutes for BioMedical Research, WKL-136.4.25, CH-4002 Basel, Switzerland. patricia.imbach@novartis.com
Lang
Marc
M
García-Echeverría
Carlos
C
Guagnano
Vito
V
Noorani
Maria
M
Roesel
Johannes
J
Bitsch
Francis
F
Rihs
Grety
G
Furet
Pascal
P
D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D061988:Proteasome Inhibitors; D013329:Structure-Activity Relationship; D014361:Trypsin Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000494:pharmacology*
D010455:Peptides; D061988:Proteasome Inhibitors; D014361:Trypsin Inhibitors; D047090:beta-Lactams; D002918:Chymotrypsin