ArticlePloS one2022
Characterization of a KDM5 small molecule inhibitor with antiviral activity against hepatitis B virus.
Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Associations Between Employment and Health Outcomes: A Systematic Review of Reviews.Journal of occupational rehabilitation · 2026Pooled it
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- Epigenetic drugs against human DNA viruses and retroviruses.Antiviral research · 2025Review
- Review
- Endothelial KDM5B Regulated by Piezo1 Contributes to Disturbed Flow Induced Atherosclerotic Plaque Formation.Journal of cellular and molecular medicine · 2024Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- SMC5/6-Mediated Transcriptional Regulation of Hepatitis B Virus and Its Therapeutic Potential.Viruses · 2024Review
- Histone demethylase enzymes KDM5A and KDM5B modulate immune response by suppressing transcription of endogenous retroviral elements.bioRxiv : the preprint server for biology · 2024Article
- KDM5 family as therapeutic targets in breast cancer: Pathogenesis and therapeutic opportunities and challenges.Molecular cancer · 2024Review
- Oxygen-dependent histone lysine demethylase 4 restricts hepatitis B virus replication.The Journal of biological chemistry · 2024Article
- Recent developments in catalysis and inhibition of the Jumonji histone demethylases.Current opinion in structural biology · 2023Review
- Review
- The catalytic domains of all human KDM5 JmjC demethylases catalyse N-methyl arginine demethylation.FEBS letters · 2023Article
- Toward a complete cure for chronic hepatitis B: Novel therapeutic targets for hepatitis B virus.Clinical and molecular hepatology · 2022Review
Corrections and comments
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Authors and funding
27 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic hepatitis B (CHB) is a global health care challenge and a major cause of liver disease. To find new therapeutic avenues with a potential to functionally cure chronic Hepatitis B virus (HBV) infection, we performed a focused screen of epigenetic modifiers to identify potential inhibitors of replication or gene expression. From this work we identified isonicotinic acid inhibitors of the histone lysine demethylase 5 (KDM5) with potent anti-HBV activity. To enhance the cellular permeability and liver accumulation of the most potent KDM5 inhibitor identified (GS-080) an ester prodrug was developed (GS-5801) that resulted in improved bioavailability and liver exposure as well as an increased H3K4me3:H3 ratio on chromatin. GS-5801 treatment of HBV-infected primary human hepatocytes reduced the levels of HBV RNA, DNA and antigen. Evaluation of GS-5801 antiviral activity in a humanized mouse model of HBV infection, however, did not result in antiviral efficacy, despite achieving pharmacodynamic levels of H3K4me3:H3 predicted to be efficacious from the in vitro model. Here we discuss potential reasons for the disconnect between in vitro and in vivo efficacy, which highlight the translational difficulties of epigenetic targets for viral diseases.
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