title: Entry into a new class of potent proteasome inhibitors having high antiproliferative activity by structure-based design.
abstract: Proteasome inhibition is a therapeutic concept of current interest in anticancer research. We report here the design, synthesis, and biological characterization of prototypes of a new class of noncovalent proteasome inhibitors showing high activity in biochemical and cellular assays.
authors.affiliation: Novartis Pharma AG, Novartis Institutes for Biomedical Research, CH-4002 Basel, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Furet
authors.forename: Patricia
authors.initials: P
authors.lastname: Imbach
authors.forename: Maria
authors.initials: M
authors.lastname: Noorani
authors.forename: Juergen
authors.initials: J
authors.lastname: Koeppler
authors.forename: Kurt
authors.initials: K
authors.lastname: Laumen
authors.forename: Marc
authors.initials: M
authors.lastname: Lang
authors.forename: Vito
authors.initials: V
authors.lastname: Guagnano
authors.forename: Peter
authors.initials: P
authors.lastname: Fuerst
authors.forename: Johannes
authors.initials: J
authors.lastname: Roesel
authors.forename: Johann
authors.initials: J
authors.lastname: Zimmermann
authors.forename: Carlos
authors.initials: C
authors.lastname: García-Echeverría
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C492675:3-phenoxyphenylalanyl-3,4,5-trimethoxyphenylalanyl-valine 2-hydroxy-4-methoxybenzyl amide; D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D009842:Oligopeptides; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex