{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:21:56Z","timestamp":1791570116565,"version":"4.3.4"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["NIH Grant 1-R01-AI-132833"],"award-info":[{"award-number":["NIH Grant 1-R01-AI-132833"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5P30-AI-50409"],"award-info":[{"award-number":["5P30-AI-50409"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>While treatment options are available for hepatitis B virus (HBV), there is currently no cure. Anti-HBV nucleoside analogs and interferon-alpha 2b rarely clear HBV covalently closed circular DNA (cccDNA), requiring lifelong treatment. Recently, we identified GLP-26, a glyoxamide derivative which modulates HBV capsid assembly. The impact of GLP-26 on viral replication and integrated DNA was assessed in an HBV nude mouse model bearing HBV transfected AD38 xenografts. At day 45 post-infection, GLP-26 reduced HBV titers by 2.3\u20133 log10 versus infected placebo-treated mice. Combination therapy with GLP-26 and entecavir reduced HBV log10 titers by 4.6-fold versus placebo. Next, we examined the pharmacokinetics (PK) in cynomolgus monkeys administered GLP-26 via IV (1 mg\/kg) or PO (5 mg\/kg). GLP-26 was found to have 34% oral bioavailability, with a mean input time of 3.17 h. The oral dose produced a mean peak plasma concentration of 380.7 ng\/mL, observed 0.67 h after administration (~30-fold &gt; in vitro EC90 corrected for protein binding), with a mean terminal elimination half-life of 2.4 h and a mean area under the plasma concentration versus time curve of 1660 ng\u00b7hr\/mL. GLP-26 was 86.7% bound in monkey plasma. Lastly, GLP-26 demonstrated a favorable toxicity profile confirmed in primary human cardiomyocytes. Thus, GLP-26 warrants further preclinical development as an add on to treatment for HBV infection.<\/jats:p>","DOI":"10.3390\/v13010114","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T02:36:05Z","timestamp":1611196565000},"page":"114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Studies on the Efficacy, Potential Cardiotoxicity and Monkey Pharmacokinetics of GLP-26 as a Potent Hepatitis B Virus Capsid Assembly Modulator"],"prefix":"10.3390","volume":"13","author":[{"given":"Selwyn J.","family":"Hurwitz","sequence":"first","affiliation":[{"name":"Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noreen","family":"McBrearty","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla","family":"Arzumanyan","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Bichenkov","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Tao","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda","family":"Bassit","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Kohler","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Amblard","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Feitelson","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond F.","family":"Schinazi","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, 1760 Haygood Drive, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nicolini, L.A., Orsi, A., Tatarelli, P., Viscoli, C., Icardi, G., and Sticchi, L. 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