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

Patricia Imbach; Marc Lang; Carlos García-Echeverría; Vito Guagnano; Maria Noorani; Johannes Roesel; Francis Bitsch; Grety Rihs; Pascal Furet

doi:10.1016/j.bmcl.2006.10.047

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

Bioorg Med Chem Lett. 2007 Jan 15;17(2):358-62. doi: 10.1016/j.bmcl.2006.10.047. Epub 2006 Oct 24.

Authors

Patricia Imbach¹, Marc Lang, Carlos García-Echeverría, Vito Guagnano, Maria Noorani, Johannes Roesel, Francis Bitsch, Grety Rihs, Pascal Furet

Affiliation

¹ Novartis Institutes for BioMedical Research, WKL-136.4.25, CH-4002 Basel, Switzerland. [email protected]

PMID: 17095212
DOI: 10.1016/j.bmcl.2006.10.047

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.

MeSH terms

Chymotrypsin / antagonists & inhibitors*
Crystallography, X-Ray
Drug Design
Humans
Models, Molecular
Peptides / chemistry
Proteasome Inhibitors*
Structure-Activity Relationship
Trypsin Inhibitors / chemical synthesis*
Trypsin Inhibitors / pharmacology*
beta-Lactams / chemical synthesis*
beta-Lactams / pharmacology*

Substances

Peptides
Proteasome Inhibitors
Trypsin Inhibitors
beta-Lactams
Chymotrypsin