Development of peptide epoxyketones as selective immunoproteasome inhibitors
文献类型：期刊论文
| 作者 | Li, Xuemei1; Hong, Duidui2; Zhang, Mengmeng3; Xu, Lei3,4; Zhou, Yubo3,4,5 ; Li, Jia3,4,5; Liu, Tao1
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2021-10-05 |
| 卷号 | 221页码:113556 |
| 关键词 | Epoxyketones Immunoproteasome inhibitor Selectivity Multiple myeloma |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2021.113556 |
| 文献子类 | Article |
| 英文摘要 | A series of epoxyketone analogues with varying N-caps and P3-configurations were designed, synthesized and evaluated. We found that D-Ala in P3 was crucial for beta 5i selectivity over beta 5c. Notably, compounds 20j (beta 5i IC50 = 26.0 nM, 25-fold selectivity) and 20l (beta 5i IC50 = 25.1 nM, 24-fold selectivity) with the D-configuration at P3 were the most selective inhibitors. Although 20j and 20l showed only moderate anti-proliferative activity against RPMI-8226 and MM.1S cell lines, based on our experiments, it indicates that the inhibition of beta 5i alone is not sufficient to exert anticancer effects and may rely on the complementary inhibition of beta 1i, beta 5c and beta 5i. These data further increase our understanding of immunoproteasome inhibitors in hematologic malignancies. (C) 2021 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | MULTIPLE-MYELOMA ; PROTEASOME ; DISCOVERY ; DESIGN ; YEAST |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000661282500044 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309384]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhou, Yubo; Li, Jia; Liu, Tao |
| 作者单位 | 1.Zhejiang Univ, ZJU ENS Joint Lab Med Chem, Zhejiang Prov Key Lab Anticanc Drug Res, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China; 2.Jiangsu Shengdia Ind Co Ltd, 161 Shaoxing Rd, Hangzhou 310004, Peoples R China; 3.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Inst Drug Discovery Innovat, Zhongshan 528400, Peoples R China; 5.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Xuemei,Hong, Duidui,Zhang, Mengmeng,et al. Development of peptide epoxyketones as selective immunoproteasome inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2021,221:113556. |
| APA | Li, Xuemei.,Hong, Duidui.,Zhang, Mengmeng.,Xu, Lei.,Zhou, Yubo.,...&Liu, Tao.(2021).Development of peptide epoxyketones as selective immunoproteasome inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,221,113556. |
| MLA | Li, Xuemei,et al."Development of peptide epoxyketones as selective immunoproteasome inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 221(2021):113556. |
入库方式： OAI收割
来源：上海药物研究所
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