title: Novel beta-lactam derivatives: potent and selective inhibitors of the chymotrypsin-like activity of the human 20S proteasome.
abstract: 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.
authors.affiliation: Novartis Institutes for BioMedical Research, WKL-136.4.25, CH-4002 Basel, Switzerland. patricia.imbach@novartis.com
authors.forename: Patricia
authors.initials: P
authors.lastname: Imbach
authors.forename: Marc
authors.initials: M
authors.lastname: Lang
authors.forename: Carlos
authors.initials: C
authors.lastname: García-Echeverría
authors.forename: Vito
authors.initials: V
authors.lastname: Guagnano
authors.forename: Maria
authors.initials: M
authors.lastname: Noorani
authors.forename: Johannes
authors.initials: J
authors.lastname: Roesel
authors.forename: Francis
authors.initials: F
authors.lastname: Bitsch
authors.forename: Grety
authors.initials: G
authors.lastname: Rihs
authors.forename: Pascal
authors.initials: P
authors.lastname: Furet
mesh_terms: 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*
chemical_list: D010455:Peptides; D061988:Proteasome Inhibitors; D014361:Trypsin Inhibitors; D047090:beta-Lactams; D002918:Chymotrypsin