Development of HSP90 inhibitors-SN38 conjugates for cancer treatment
文献类型：期刊论文
| 作者 | Cao, Yuting1; Shen, Qianqian2; Ding, Mengyuan1; Chen, Yi2 ; Lu, Wei1; Zhu, Shulei1
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| 刊名 | BIOORGANIC CHEMISTRY
 |
| 出版日期 | 2023-08-01 |
| 卷号 | 137页码:11 |
| 关键词 | HSP90 SN38 conjugate Drug accumulation Cancer treatment |
| ISSN号 | 0045-2068 |
| DOI | 10.1016/j.bioorg.2023.106582 |
| 通讯作者 | Chen, Yi(ychen@simm.ac.cn) ; Lu, Wei(wlu@chem.ecnu.edu.cn) ; Zhu, Shulei(slzhu@chem.ecnu.edu.cn) |
| 英文摘要 | Presently, chemotherapy remains to be one of the most important therapeutic approaches for malignant tumors. Ligands based drug conjugates are showing considerable promise as potential therapeutic agents delivery sys-tems for cancer. Here, a series of HSP90 inhibitors-SN38 conjugates were developed through cleavable linkers for tumor-specific delivery of SN38 and reducing its side effects. In vitro assays showed that these conjugates exhibited acceptable stability in PBS and plasma, appreciable HSP90 binding affinity, and potent cytotoxic abilities. Cellular uptake behaviors also indicated that these conjugates could selectively target cancer cells in a time-dependent manner via HSP90. Among them, compound 10b with a glycine linkage exhibits appreciable in vitro and in vivo pharmacokinetic profiles, and excellent in vivo antitumor activity in Capan-1 xenograft models, demonstrating the selective targeting and accumulation of the active payload at tumor sites. Above all, these results suggest that compound 10b has the potential as a potent anticancer drug, meriting further evaluation in the future. |
| WOS关键词 | DELIVERY ; THERAPY |
| 资助项目 | Fundamental Research Funds for the Central Universities ; National Natural Science Foundation of China[22077034] ; National Natural Science Foundation of China[82104000] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001000571100001 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306692]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Yi; Lu, Wei; Zhu, Shulei |
| 作者单位 | 1.East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug Dev, Sch Chem & Mol Engn, Shanghai 200062, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cao, Yuting,Shen, Qianqian,Ding, Mengyuan,et al. Development of HSP90 inhibitors-SN38 conjugates for cancer treatment[J]. BIOORGANIC CHEMISTRY,2023,137:11. |
| APA | Cao, Yuting,Shen, Qianqian,Ding, Mengyuan,Chen, Yi,Lu, Wei,&Zhu, Shulei.(2023).Development of HSP90 inhibitors-SN38 conjugates for cancer treatment.BIOORGANIC CHEMISTRY,137,11. |
| MLA | Cao, Yuting,et al."Development of HSP90 inhibitors-SN38 conjugates for cancer treatment".BIOORGANIC CHEMISTRY 137(2023):11. |
入库方式： OAI收割
来源：上海药物研究所
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