High-Throughput Screening of Low Molecular Weight NS3-NS4A Protease Inhibitors Using a Fluorescence Resonance Energy Transfer Substrate-Reference-Cited by-同舟云学术

High-Throughput Screening of Low Molecular Weight NS3-NS4A Protease Inhibitors Using a Fluorescence Resonance Energy Transfer Substrate

Published:2005-12 Issue:6 Volume:16 Page:385-392
ISSN:2040-2066
Container-title:Antiviral Chemistry and Chemotherapy
language:en
Short-container-title:Antivir Chem Chemother

Author:

Sudo Kenji¹,Yamaji Kayo²,Kawamura Kouich²,Nishijima Tomoko²,Kojima Naoko²,Aibe Kazuhiko²,Shimotohno Kunitada³,Shimizu Yasuaki²

Affiliation:

1. Rational Drug Design Laboratories, Fukushima, Japan

2. Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Ibaraki, Japan

3. Virology Division, National Cancer Center Research Institute, Tokyo, Japan

Abstract

Hepatitis C virus (HCV) NS3-NS4A protease is an attractive target for anti-HCV agents because of its important role in replication. An optimized fluorescence resonance energy transfer (FRET) substrate for NS3-NS4A protease, based on the sequence of the NS5A-5B cleavage site, was designed and synthesized. High-throughput screening of in-house compound libraries was performed using a FRET substrate FS10 (MOCAc-DKIVPC-SMSYK-Dnp) and MBP-NS3-NS4A fusion protein. Several hit compounds were found, including YZ-9577 (2-oxido-1,2,5-oxadiazole-3,4-diyl) bis (phenylmethanone) with potent inhibitory activity (IC50=1.6 μM) and good selectivity against other human serine proteases.

Publisher

SAGE Publications

Link

http://journals.sagepub.com/doi/pdf/10.1177/095632020501600605

Reference37 articles.

1. Kinetic and structural analyses of hepatitis C virus polyprotein processing

2. Genetic organization and diversity of the hepatitis C virus.

3. Isolation and structure of SCH 351633: a novel hepatitis C virus (HCV) NS3 protease inhibitor from the fungus Penicillium griseofulvum

4. Phenethyl Amides as Novel Noncovalent Inhibitors of Hepatitis C Virus NS3/4A Protease: Discovery, Initial SAR, and Molecular Modeling

5. Approaching a new era for hepatitis C virus therapy: inhibitors of the NS3-4A serine protease and the NS5B RNA-dependent RNA polymerase

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