A new structural class of selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome

C García-Echeverría; P Imbach; D France; P Fürst; M Lang; A M Noorani; D Scholz; J Zimmermann; P Furet

doi:10.1016/s0960-894x(01)00205-0

A new structural class of selective and non-covalent inhibitors of the chymotrypsin-like activity of the 20S proteasome

Bioorg Med Chem Lett. 2001 May 21;11(10):1317-9. doi: 10.1016/s0960-894x(01)00205-0.

Authors

C García-Echeverría¹, P Imbach, D France, P Fürst, M Lang, A M Noorani, D Scholz, J Zimmermann, P Furet

Affiliation

¹ Oncology Research, Novartis Pharma Inc, Basel, Switzerland. [email protected]

PMID: 11392545
DOI: 10.1016/s0960-894x(01)00205-0

Abstract

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.

MeSH terms

Amino Acids / chemistry
Anti-Inflammatory Agents / chemical synthesis
Antineoplastic Agents / chemical synthesis
Chymotrypsin
Cysteine Endopeptidases / metabolism
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Humans
Inhibitory Concentration 50
Multienzyme Complexes / antagonists & inhibitors*
Multienzyme Complexes / metabolism
Oligopeptides / chemical synthesis
Oligopeptides / pharmacology
Peptide Library
Proteasome Endopeptidase Complex
Protein Binding
Structure-Activity Relationship

Substances

Amino Acids
Anti-Inflammatory Agents
Antineoplastic Agents
Enzyme Inhibitors
Multienzyme Complexes
Oligopeptides
Peptide Library
Chymotrypsin
Cysteine Endopeptidases
Proteasome Endopeptidase Complex
statine