Ontology highlight
ABSTRACT:
SUBMITTER: Geurink PP
PROVIDER: S-EPMC3782865 | biostudies-literature | 2013 Feb
REPOSITORIES: biostudies-literature
Geurink Paul P PP van der Linden Wouter A WA Mirabella Anne C AC Gallastegui Nerea N de Bruin Gerjan G Blom Annet E M AE Voges Mathias J MJ Mock Elliot D ED Florea Bogdan I BI van der Marel Gijs A GA Driessen Christoph C van der Stelt Mario M Groll Michael M Overkleeft Herman S HS Kisselev Alexei F AF
Journal of medicinal chemistry 20130128 3
Proteasomes degrade the majority of proteins in mammalian cells by a concerted action of three distinct pairs of active sites. The chymotrypsin-like sites are targets of antimyeloma agents bortezomib and carfilzomib. Inhibitors of the trypsin-like site sensitize multiple myeloma cells to these agents. Here we describe systematic effort to develop inhibitors with improved potency and cell permeability, yielding azido-Phe-Leu-Leu-4-aminomethyl-Phe-methyl vinyl sulfone (4a, LU-102), and a fluoresce ...[more]