ArticleEuropean journal of medicinal chemistry2012
Discovery of new scaffolds for rational design of HCV NS5B polymerase inhibitors.
Article in European journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The trial behind it
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Integrated deep learning and multi-scale modeling for the discovery of pan-genotypic HCV NS5B polymerase inhibitors.Molecular diversity · 2026Article
- Virtual screening, optimization design, and synthesis analysis of novel benzofuran derivatives as pan-genotypic HCV NS5B polymerase inhibitors using molecular modeling.BMC chemistry · 2025Article
- The IQA Energy Partition in a Drug Design Setting: A Hepatitis C Virus RNA-Dependent RNA Polymerase (NS5B) Case Study.Pharmaceuticals (Basel, Switzerland) · 2022Article
- StackHCV: a web-based integrative machine-learning framework for large-scale identification of hepatitis C virus NS5B inhibitors.Journal of computer-aided molecular design · 2021Article
- Article
- Combination of pharmacophore hypothesis and molecular docking to identify novel inhibitors of HCV NS5B polymerase.Molecular diversity · 2015Article
- Discovery of the 2-phenyl-4,5,6,7-Tetrahydro-1H-indole as a novel anti-hepatitis C virus targeting scaffold.European journal of medicinal chemistry · 2015Article
- 2-Heteroarylimino-5-arylidene-4-thiazolidinones as a new class of non-nucleoside inhibitors of HCV NS5B polymerase.European journal of medicinal chemistry · 2013Article
- Design and synthesis of L- and D-phenylalanine derived rhodanines with novel C5-arylidenes as inhibitors of HCV NS5B polymerase.Bioorganic & medicinal chemistry · 2013Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Hepatitis C virus (HCV) NS5B polymerase is a key target for the development of anti-HCV drugs. Here we report on the identification of novel allosteric inhibitors of HCV NS5B through a combination of structure-based virtual screening and in vitro NS5B inhibition assays. One hundred and sixty thousand compounds from the Otava database were virtually screened against the thiazolone inhibitor binding site on NS5B (thumb pocket-2, TP-2), resulting in a sequential down-sizing of the library by 2.7 orders of magnitude to yield 59 NS5B non-nucleoside inhibitor (NNI) candidates. In vitro evaluation of the NS5B inhibitory activity of the 59 selected compounds resulted in a 14% hit rate, yielding 8 novel structural scaffolds. Of these, compound 1 bearing a 4-hydrazinoquinazoline scaffold was the most active (IC(50) = 16.0 μM). The binding site of all 8 NNIs was mapped to TP-2 of NS5B as inferred by a decrease in their inhibition potency against the M423T NS5B mutant, employed as a screen for TP-2 site binders. At 100 μM concentration, none of the eight compounds exhibited any cytotoxicity, and all except compound 8 exhibited between 40 and 60% inhibition of intracellular NS5B polymerase activity in BHK-NS5B-FRLuc reporter cells. These inhibitor scaffolds will form the basis for future optimization and development of more potent NS5B inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.