A new structural class of selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome.
We describe the identification and in vitro characterization of a series of 2-aminobenzylstatine derivatives that inhibit non-covalently the chymotrypsin-like activity of the 20S proteasome. Our initial SAR data demonstrate that the 2-aminobenzylstatine core structure can effectively serve as the basis for designing potent, selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome.
García-Echeverría
C
C
Oncology Research, Novartis Pharma Inc, Basel, Switzerland. carlos.garcia-echeverria@pharma.novartis.com
Imbach
P
P
France
D
D
Fürst
P
P
Lang
M
M
Noorani
A M
AM
Scholz
D
D
Zimmermann
J
J
Furet
P
P
D000596:Amino Acids / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D019151:Peptide Library; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D009842:Oligopeptides; D019151:Peptide Library; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C013165:statine