An ATG4B inhibitor blocks autophagy and sensitizes Sorafenib inhibition activities in HCC tumor cells
文献类型：期刊论文
| 作者 | Xie, Yanqiu7,8; Fan, Shijie6,7; Ni, Dongxuan3,4,5; Wan, Wei7; Xu, Pan7; Ding, Yiluan7; Zhang, Ruihan4,5; Lu, Jing8; Zhang, Naixia7 ; Zhang, Yuanyuan7
|
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
 |
| 出版日期 | 2023-04-15 |
| 卷号 | 84页码:117262 |
| 关键词 | ATG4B inhibitor DC-ATG4in Sorafenib Hepatocellular Carcinoma Combination therapy |
| DOI | 10.1016/j.bmc.2023.117262 |
| 文献子类 | Article |
| 英文摘要 | Autophagy related 4B (ATG4B) which regulates autophagy by promoting the formation of autophagosome through reversible modification of LC3, is closely related to cancer cell growth and drug resistance, and therefore is an attractive therapeutic target. Recently, ATG4B inhibitors have been reported, yet with drawbacks including weak potency. To discover more promising ATG4B inhibitors, we developed a high-throughput screening (HTS) assay and identified a new ATG4B inhibitor named DC-ATG4in. DC-ATG4in directly binds to ATG4B and inhibits its enzyme activity with an IC50 of 3.08 +/- 0.47 mu M. We further confirmed that DC-ATG4in is an autophagy inhibitor and blocks autophagy induced by Sorafenib in Hepatocellular Carcinoma (HCC) cells. More impor-tantly, combination of DC-ATG4in with Sorafenib synergized the cancer cell killing effect and proliferation in-hibition activities on HCC cells. Our data suggested that inactivation of autophagy via ATG4B inhibition may be a viable strategy to sensitize existing targeted therapy such as Sorafenib in the future. |
| WOS关键词 | CANCER ; MECHANISM ; DISEASE ; TARGET ; ENZYME |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000972393400001 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309654]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Xiao, Weilie; Zhao, Kehao; Luo, Cheng |
| 作者单位 | 1.Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou 310053, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Zhongshan Inst Drug Discovery, Zhongshan 528437, Peoples R China; 3.Yunnan Univ, State Key Lab Conservat & Utilizat Bioresources Yu, Kunming 650091, Peoples R China; 4.Yunnan Univ, Sch Med, Kunming 650500, Peoples R China; 5.Yunnan Univ, Key Lab Med Chem Nat Resource, Minist Educ, Yunnan Characterist Plant Extract Lab,Yunnan Res &, Kunming 650500, Peoples R China; 6.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 8.Yantai Univ, Collaborat Innovat Ctr Adv Drug Delivery Syst & Bi, Minist Educ, Sch Pharm,Key Lab Mol Pharmacol & Drug Evaluat, Yantai 264005, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xie, Yanqiu,Fan, Shijie,Ni, Dongxuan,et al. An ATG4B inhibitor blocks autophagy and sensitizes Sorafenib inhibition activities in HCC tumor cells[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2023,84:117262. |
| APA | Xie, Yanqiu.,Fan, Shijie.,Ni, Dongxuan.,Wan, Wei.,Xu, Pan.,...&Luo, Cheng.(2023).An ATG4B inhibitor blocks autophagy and sensitizes Sorafenib inhibition activities in HCC tumor cells.BIOORGANIC & MEDICINAL CHEMISTRY,84,117262. |
| MLA | Xie, Yanqiu,et al."An ATG4B inhibitor blocks autophagy and sensitizes Sorafenib inhibition activities in HCC tumor cells".BIOORGANIC & MEDICINAL CHEMISTRY 84(2023):117262. |
入库方式： OAI收割
来源：上海药物研究所
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