Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors

…, F Marsilio, B Fang, WC Guida, J Koomen…

Index: Ozcan, Sevil; Kazi, Aslamuzzaman; Marsilio, Frank; Fang, Bin; Guida, Wayne C.; Koomen, John; Lawrence, Harshani R.; Sebti, Said M. Journal of Medicinal Chemistry, 2013 , vol. 56, # 10 p. 3783 - 3805

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Citation Number: 10

Abstract

Screening of the 50 000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50= 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (TL) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC–MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library ...