{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["15(15)"],"submitter":["Yuan S"],"pubmed_abstract":["<b>Background:</b> Liver fibrosis, characterized by excessive extracellular matrix deposition, is a precursor to cirrhosis and hepatocellular carcinoma, and current treatments are often limited by off-target toxicities. <b>Methods and results:</b> We repurposed the liver-targeting chimera (LIVTAC) XZ1606, a novel proteolysis-targeting chimera (PROTAC) conjugated with a triantennary <i>N</i>-acetylgalactosamine (tri-GalNAc) moiety, to degrade BRD4 in hepatic stellate cells. <i>In vitro</i>, XZ1606 induced potent, dose- and time-dependent BRD4 degradation in LX-2 cells via the ubiquitin-proteasomal pathway after ASGPR-mediated endocytosis, with minimal cytotoxicity in normal hepatocytes. TGF-β-activated LX-2 cells exhibited significant reductions in fibrotic markers upon treatment, correlati"],"journal":["Theranostics"],"pagination":["7270-7290"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12315693"],"repository":["biostudies-literature"],"pubmed_title":["Liver-targeted degradation of BRD4 reverses hepatic fibrosis and enhances metabolism in murine models."],"pmcid":["PMC12315693"],"pubmed_authors":["Yuan S","Pan Y","Wang Q","He Y","Dong X","Guo Y","Zi M","Zhang X","Chen C","Nisar A","Khan S"],"additional_accession":[]},"is_claimable":false,"name":"Liver-targeted degradation of BRD4 reverses hepatic fibrosis and enhances metabolism in murine models.","description":"<b>Background:</b> Liver fibrosis, characterized by excessive extracellular matrix deposition, is a precursor to cirrhosis and hepatocellular carcinoma, and current treatments are often limited by off-target toxicities. <b>Methods and results:</b> We repurposed the liver-targeting chimera (LIVTAC) XZ1606, a novel proteolysis-targeting chimera (PROTAC) conjugated with a triantennary <i>N</i>-acetylgalactosamine (tri-GalNAc) moiety, to degrade BRD4 in hepatic stellate cells. <i>In vitro</i>, XZ1606 induced potent, dose- and time-dependent BRD4 degradation in LX-2 cells via the ubiquitin-proteasomal pathway after ASGPR-mediated endocytosis, with minimal cytotoxicity in normal hepatocytes. TGF-β-activated LX-2 cells exhibited significant reductions in fibrotic markers upon treatment, correlati","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025","modification":"2025-08-27T03:07:03.125Z","creation":"2025-08-27T03:07:03.125Z"},"accession":"S-EPMC12315693","cross_references":{"pubmed":["40756370"],"doi":["10.7150/thno.113852"]}}