{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:36:26Z","timestamp":1790753786872,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T00:00:00Z","timestamp":1663372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T00:00:00Z","timestamp":1663372800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims:<\/jats:title>\n                    <jats:p>In the treatment of chronic hepatitis B (CHB) infection, stimulation of innate immunity may lead to hepatitis B virus (HBV) cure. Alpha\u2010kinase 1 (ALPK1) is a pattern recognition receptor (PRR) that activates the NF\u2010\u03baB pathway and stimulates innate immunity. Here we characterized the preclinical anti\u2010HBV efficacy of DF\u2010006, an orally active agonist of ALPK1 currently in clinical development for CHB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results:<\/jats:title>\n                    <jats:p>In adeno\u2010associated virus (AAV)\u2010HBV mouse models and primary human hepatocytes (PHHs) infected with HBV, we evaluated the antiviral efficacy of DF\u2010006. In the mouse models, DF\u2010006 rapidly reduced serum HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen levels using doses as low as 0.08 \u03bcg\/kg, 1 \u03bcg\/kg, and 5\u2009\u03bcg\/kg, respectively. DF\u2010006 in combination with the HBV nucleoside reverse transcriptase inhibitor, entecavir, further reduced HBV DNA. Antiviral efficacy in mice was associated with an increase in immune cell infiltration and decrease of hepatitis B core antigen, encapsidated pregenomic RNA, and covalently closed circular DNA in liver. At subnanomolar concentrations, DF\u2010006 also showed anti\u2010HBV efficacy in PHH with significant reductions of HBV DNA. Following dosing with DF\u2010006, there was upregulation of NF\u2010\u03baB\u2010targeted genes that are involved in innate immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>DF\u2010006 was efficacious in mouse and PHH models of HBV without any indications of overt toxicity. In mice, DF\u2010006 localized primarily to the liver where it potently activated innate immunity. The transcriptional response in mouse liver provides insights into mechanisms that mediate anti\u2010HBV efficacy by DF\u2010006.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.32614","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T10:33:53Z","timestamp":1655202833000},"page":"275-289","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":23,"title":["Alpha\u2010kinase 1 (ALPK1) agonist DF\u2010006 demonstrates potent efficacy in mouse and primary human hepatocyte (PHH) models of hepatitis B"],"prefix":"10.1097","volume":"77","author":[{"given":"Cong","family":"Xu","sequence":"first","affiliation":[{"name":"Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China"},{"name":"Zhejiang Yao Yuan Biotechnology Ltd, Jiashan, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieqing","family":"Fan","sequence":"additional","affiliation":[{"name":"Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China"},{"name":"Zhejiang Yao Yuan Biotechnology Ltd, Jiashan, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China"},{"name":"Zhejiang Yao Yuan Biotechnology Ltd, Jiashan, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimaier","family":"Tuerdi","sequence":"additional","affiliation":[{"name":"Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuning","family":"Wei","sequence":"additional","affiliation":[{"name":"Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Pan","sequence":"additional","affiliation":[{"name":"Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaixin","family":"Dang","sequence":"additional","affiliation":[{"name":"Zhejiang Yao Yuan Biotechnology Ltd, Jiashan, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Wei","sequence":"additional","affiliation":[{"name":"Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf Siddig","family":"Yousif","sequence":"additional","affiliation":[{"name":"Drug Farm USA, Lowell, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeysen","family":"Yogaratnam","sequence":"additional","affiliation":[{"name":"Drug Farm USA, Lowell, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Biology Department, Wuxi Apptec (Shanghai) Co. 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