title: Structure-based optimisation of 2-aminobenzylstatine derivatives: potent and selective inhibitors of the chymotrypsin-like activity of the human 20S proteasome.
abstract: We have identified 2-aminobenzylstatine derivatives that inhibit non-covalently the chymotrypsin-like activity of the human 20S proteasome. A structure-based optimisation approach has allowed us to improve the potency of this structural class of proteasome inhibitors from micromolar to nanomolar level. The new derivatives showed good selectivity against the trypsin-like and post-glutamyl-peptide hydrolytic activities of this enzyme.
authors: Oncology Research, Novartis Pharma Inc., CH-4002, Basel, Switzerland. pascal.furet@pharma.novartis.com
authors: Pascal
authors: P
authors: Furet
authors: Patricia
authors: P
authors: Imbach
authors: Peter
authors: P
authors: Fuerst
authors: Marc
authors: M
authors: Lang
authors: Maria
authors: M
authors: Noorani
authors: Johann
authors: J
authors: Zimmermann
authors: Carlos
authors: C
authors: García-Echeverría
mesh_terms: D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002918:Chymotrypsin / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D013329:Structure-Activity Relationship
chemical_list: D001593:Benzyl Compounds; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex