{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ji X"],"funding":["Shandong Provincial Key Research and Development Project","The Agency for Medical Research and Development","The Japan Society for the Promotion of Science KAKENHI","Science Foundation for Outstanding Young Scholars of Shandong Province","Foreign Cultural and Educational Experts Project"],"pagination":["5987"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9505734"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(18)"],"pubmed_abstract":["Hepatitis B virus (HBV) capsid protein (Cp) is necessary for viral replication and the maintenance of viral persistence, having become an attractive target of anti-HBV drugs. To improve the water solubility of HBV capsid protein allosteric modulator (CpAM) NVR 3-778, a series of novel carboxylic acid and phosphate prodrugs were designed and synthesized using a prodrug strategy. In vitro HBV replication assay showed that these prodrugs maintained favorable antiviral potency (EC<sub>50</sub> = 0.28-0.42 µM), which was comparable to that of NVR 3-778 (EC<sub>50</sub> = 0.38 µM). More importantly, the cytotoxicity of prodrug <b>N8</b> (CC<sub>50</sub> &gt; 256 µM) was significantly reduced compared to NVR 3-778 (CC<sub>50</sub> = 13.65 ± 0.21 µM). In addition, the water solubility of prodrug <"],"journal":["Molecules (Basel, Switzerland)"],"pubmed_title":["Design, Synthesis, and Evaluation of a Set of Carboxylic Acid and Phosphate Prodrugs Derived from HBV Capsid Protein Allosteric Modulator NVR 3-778."],"pmcid":["PMC9505734"],"funding_grant_id":["No. 2019JZZY021011","ZR2020JQ31","GXL20200015001","Grant No. JP20H03499, JP61H02449","Grant Nos. JP21jm0210068, JP22fk0310504, JP22wm0325007, JP22fk0310511"],"pubmed_authors":["Ren Y","Liu X","Zhan P","Ji X","Zhao S","Kobayashi C","Kang D","Jiang X","Jia R","Zhang X","Gao Z","Watashi K","Hu L"],"additional_accession":[]},"is_claimable":false,"name":"Design, Synthesis, and Evaluation of a Set of Carboxylic Acid and Phosphate Prodrugs Derived from HBV Capsid Protein Allosteric Modulator NVR 3-778.","description":"Hepatitis B virus (HBV) capsid protein (Cp) is necessary for viral replication and the maintenance of viral persistence, having become an attractive target of anti-HBV drugs. To improve the water solubility of HBV capsid protein allosteric modulator (CpAM) NVR 3-778, a series of novel carboxylic acid and phosphate prodrugs were designed and synthesized using a prodrug strategy. In vitro HBV replication assay showed that these prodrugs maintained favorable antiviral potency (EC<sub>50</sub> = 0.28-0.42 µM), which was comparable to that of NVR 3-778 (EC<sub>50</sub> = 0.38 µM). More importantly, the cytotoxicity of prodrug <b>N8</b> (CC<sub>50</sub> &gt; 256 µM) was significantly reduced compared to NVR 3-778 (CC<sub>50</sub> = 13.65 ± 0.21 µM). In addition, the water solubility of prodrug <","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2025-06-01T00:11:20.515Z","creation":"2025-02-19T00:41:50.819Z"},"accession":"S-EPMC9505734","cross_references":{"pubmed":["36144715"],"doi":["10.3390/molecules27185987"]}}