2133017-36-2Relevant academic research and scientific papers
Discovery and structure activity relationship of glyoxamide derivatives as anti-hepatitis B virus agents
Amblard, Franck,Boucle, Sebastien,Bassit, Leda,Chen, Zhe,Sari, Ozkan,Cox, Bryan,Verma, Kiran,Ozturk, Tugba,Ollinger-Russell, Olivia,Schinazi, Raymond F.
, (2021)
Chronic hepatitis B viral infection is a significant health problem world-wide, and currently available antiviral agents suppress HBV infections, but rarely cure this disease. It is presumed that antiviral agents that target the viral nuclear reservoir of transcriptionally active cccDNA may eliminate HBV infection. Through a series of chemical optimization, we identified a new series of glyoxamide derivatives affecting HBV nucleocapsid formation and cccDNA maintenance at low nanomolar levels. Among all the compounds synthesized, GLP-26 displays a major effect on HBV DNA, HBeAg secretion and cccDNA amplification. In addition, GLP-26 shows a promising pre-clinical profile and long-term effect on viral loads in a humanized mouse model.
Novel hepatitis B virus capsid assembly modulator induces potent antiviral responses in vitro and in humanized mice
Amblard, Franck,Boucle, Sebastien,Bassit, Leda,Cox, Bryan,Sari, Ozkan,Tao, Sijia,Chen, Zhe,Ozturk, Tugba,Verma, Kiran,Russell, Olivia,Rat, Virgile,De Rocquigny, Hugues,Fiquet, Oriane,Boussand, Maud,Di Santo, James,Strick-Marchand, Helene,Schinazi, Raymond F.
, (2020)
Hepatitis B virus (HBV) affects an estimated 250 million chronic carriers worldwide. Though several vaccines exist, they are ineffective for those already infected. HBV persists due to the formation of covalently closed circular DNA (cccDNA) the viral minichromosome in the nucleus of hepatocytes. Current nucleoside analogs and interferon therapies rarely clear cccDNA, requiring lifelong treatment. Our group identified GLP-26, a novel glyoxamide derivative that alters HBV nucleocapsid assembly and prevents viral DNA replication. GLP-26 exhibited single-digit nanomolar anti-HBV activity, inhibition of HBV e antigen (HBeAg) secretion, and reduced cccDNA amplification, in addition to showing a promising preclinical profile. Strikingly, long term combination treatment with entecavir in a humanized mouse model induced a decrease in viral loads and viral antigens that was sustained for up to 12 weeks after treatment cessation.
ELIMINATION OF HEPATITIS B VIRUS WITH ANTIVIRAL AGENTS
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, (2017/09/27)
The present invention is directed to compounds, compositions and methods for preventing, treating or curing Hepatitis B (HBV) infection in human subjects or other animal hosts. The compounds are as also pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof as pharmaceutical compositions and methods for treatment, prevention or eradication of HBV infection.
