Entry into a new class of potent proteasome inhibitors having high antiproliferative activity by structure-based design.
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.
Furet
Pascal
P
Novartis Pharma AG, Novartis Institutes for Biomedical Research, CH-4002 Basel, Switzerland.
Imbach
Patricia
P
Noorani
Maria
M
Koeppler
Juergen
J
Laumen
Kurt
K
Lang
Marc
M
Guagnano
Vito
V
Fuerst
Peter
P
Roesel
Johannes
J
Zimmermann
Johann
J
García-Echeverría
Carlos
C
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
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