Liver-targeting chimeras as a potential modality for the treatment of liver diseases
文献类型：期刊论文
| 作者 | Chen, Chuanjie5,7; Pan, Yongzhang4,5,6; Yang, Xiaoyu3; Li, Huiqin4,6; Cai, Xinhui3; He, Shengyuan7; Wang, Qiong2; Yang, Yiwen3,7; Zheng, Runzi1; Li, Huiwen5,7 |
| 刊名 | JOURNAL OF CONTROLLED RELEASE
 |
| 出版日期 | 2024-10-01 |
| 卷号 | 374页码:627-638 |
| 关键词 | ASGPR BET Hepatocellular carcinoma LIVTAC On-target toxicity PROTAC |
| ISSN号 | 0168-3659 |
| DOI | 10.1016/j.jconrel.2024.08.044 |
| 通讯作者 | He, Yonghan(heyonghan@mail.kiz.ac.cn) ; Zhang, Xuan(zhangxuan@simm.ac.cn) |
| 英文摘要 | Liver diseases pose significant challenges to global public health. In the realm of drug discovery and development, overcoming 'on-target off-tissue' effects remains a substantial barrier for various diseases. In this study, we have pioneered a Liver-Targeting Chimera (LIVTAC) approach using a proteolysis-targeting chimera (PROTAC) molecule coupled to the liver-specific asialoglycoprotein receptor (ASGPR) through an innovative linker attachment strategy for the precise induction of target protein degradation within the liver. As a proof-of-concept study, we designed XZ1606, a mammalian bromodomain and extra-terminal domain (BET)-targeting LIVTAC agent, which not only demonstrated enduring tumor suppression (over 2 months) in combination with sorafenib but also an improved safety profile, notably ameliorating the incidence of thrombocytopenia, a common and severe on-target dose-limiting toxic effect associated with conventional BET inhibitors. These encouraging results highlight the potential of LIVTAC as a versatile platform for addressing a broad spectrum of liver diseases. |
| WOS关键词 | ANTIBODY-MEDIATED DELIVERY ; PHARMACOKINETICS ; HEPATOCYTES ; DEGRADATION ; RESISTANCE ; CANCER |
| 资助项目 | National Natural Science Foundation of China[22277131] ; National Natural Science Foundation of China[82171558] ; Yunnan Fundamental Research Project[202201AS070038] ; Yunnan Fundamental Research Project[202305AH340006] ; National Key Research and Development Program of China[2023YFC3603300] ; Pioneer Hundred Talents Program of the Chinese Academy of Sciences |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001313570200001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/313341]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | He, Yonghan; Zhang, Xuan |
| 作者单位 | 1.Kunming Univ Sci & Technol, Med Sch, Lab Mol Genet Aging & Tumor, Kunming, Peoples R China 2.Chinese Acad Sci, Kunming Inst Zool, Natl Resource Ctr Nonhuman Primates, Kunming, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 4.Chinese Acad Sci, Key Lab Genet Evolut & Anim Models, Kunming, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.Chinese Acad Sci, Kunming Inst Zool, Key Lab Hlth Aging Res Yunnan Prov, Kunming, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Dev Ctr, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Chuanjie,Pan, Yongzhang,Yang, Xiaoyu,et al. Liver-targeting chimeras as a potential modality for the treatment of liver diseases[J]. JOURNAL OF CONTROLLED RELEASE,2024,374:627-638. |
| APA | Chen, Chuanjie.,Pan, Yongzhang.,Yang, Xiaoyu.,Li, Huiqin.,Cai, Xinhui.,...&Zhang, Xuan.(2024).Liver-targeting chimeras as a potential modality for the treatment of liver diseases.JOURNAL OF CONTROLLED RELEASE,374,627-638. |
| MLA | Chen, Chuanjie,et al."Liver-targeting chimeras as a potential modality for the treatment of liver diseases".JOURNAL OF CONTROLLED RELEASE 374(2024):627-638. |
入库方式： OAI收割
来源：上海药物研究所
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