ArticleAntimicrobial agents and chemotherapy2013
Preclinical characterization of GLS4, an inhibitor of hepatitis B virus core particle assembly.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 121 citations in OpenAlex.
- A First-in-Human Trial of GLS4, a Novel Inhibitor of Hepatitis B Virus Capsid Assembly, following Single- and Multiple-Ascending-Oral-Dose Studies with or without Ritonavir in Healthy Adult Volunteers.Antimicrobial agents and chemotherapy · 2019Trial
- Design, Synthesis, and Biological Evaluation of Highly Potent Boronic Acid (Boronate Ester)-Bearing Heteroaryldihydropyrimidine Derivatives as HBV Capsid Assembly Modulators.Journal of medicinal chemistry · 2025Article
- HBV p22-interacting protein C1QBP inhibits viral replication through impeding nucleocapsid formation and nuclear import.PLoS pathogens · 2025Article
- Discovery and mechanism verification of first-in-class hydrophobic tagging-based degraders of HBV core protein.Acta pharmaceutica Sinica. B · 2025Article
- Induction of hepatitis B core protein aggregation targeting an unconventional binding site.eLife · 2025Article
- Discovery of bimodal hepatitis B virus ribonuclease H and capsid assembly inhibitors.PLoS pathogens · 2025Article
- Selective depletion of HBV-infected hepatocytes by class A capsid assembly modulators requires high levels of intrahepatic HBV core protein.Antimicrobial agents and chemotherapy · 2024Article
- Article
- Binding characteristics of pyrrole-scaffold hepatitis B virus capsid inhibitors and identification of novel potent compounds.RSC advances · 2023Article
- Forthcoming Developments in Models to Study the Hepatitis B Virus Replication Cycle, Pathogenesis, and Pharmacological Advancements.ACS omega · 2023Review
- Pregenomic RNA Launch Hepatitis B Virus Replication System Facilitates the Mechanistic Study of Antiviral Agents and Drug-Resistant Variants on Covalently Closed Circular DNA Synthesis.Journal of virology · 2022Article
- Review
- Design and Synthesis of Hepatitis B Virus (HBV) Capsid Assembly Modulators and Evaluation of Their Activity in Mammalian Cell Model.Pharmaceuticals (Basel, Switzerland) · 2022Article
- [Rational selection of virologic and immunological biomarkers and therapeutic endpoints in the clinical trials of new drugs treating chronic hepatitis B].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Article
- The identification of highly efficacious functionalised tetrahydrocyclopenta[RSC medicinal chemistry · 2022Article
- Non-nucleoside structured compounds with antiviral activity-past 10 years (2010-2020).European journal of medicinal chemistry · 2022Review
- Bay41-4109-induced aberrant polymers of hepatitis b capsid proteins are removed via STUB1-promoted p62-mediated macroautophagy.PLoS pathogens · 2022Article
- Current Progress in the Development of Hepatitis B Virus Capsid Assembly Modulators: Chemical Structure, Mode-of-Action and Efficacy.Molecules (Basel, Switzerland) · 2021Review
- Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection.Emerging microbes & infections · 2021Article
- Probing the spatiotemporal patterns of HBV multiplication reveals novel features of its subcellular processes.PLoS pathogens · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Hepatitis B virus (HBV)-associated chronic liver diseases are treated with nucleoside analogs that target the virus polymerase. While these analogs are potent, drugs are needed to target other virus-encoded gene products to better block the virus replication cycle and chronic liver disease. This work further characterized GLS4 and compared it to the related BAY 41-4109, both of which trigger aberrant HBV core particle assembly, where the virus replication cycle occurs. This was done in HepAD38 cells, which replicate HBV to high levels. In vitro, GLS4 was significantly less toxic for primary human hepatocytes (P < 0.01 up to 100 μM), inhibited virus accumulation in the supernantant of HepAD38 cells (P < 0.02 up to 100 nM), inhibited HBV replicative forms in the liver with a significantly lower 50% effective concentration (EC50) (P < 0.02), and more strongly inhibited core gene expression (P < 0.001 at 100 to 200 nM) compared to BAY 41-4109. In vivo characterization was performed in nude mice inoculated with HepAD38 cells, which grew out as tumors, resulting in viremia. Treatment of mice with GLS4 and BAY 41-4109 showed strong and sustained suppression of virus DNA to about the same extents both during and after treatment. Both drugs reduced the levels of intracellular core antigen in the tumors. Alanine aminotransferase levels were normal. Tumor and total body weights were not affected by treatment. Thus, GLS4 was as potent as the prototype, BAY 41-4109, and was superior to lamivudine, in that there was little virus relapse after the end of treatment and no indication of toxicity.
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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.