中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Exploration of novel four-membered-heterocycle constructed peptidyl proteasome inhibitors with improved metabolic stability for cancer treatment

文献类型：期刊论文

作者Wang, Hanlin1,4,7; Wu, Zhaoxiao2,3; Cao, Yu5; Gao, Lixin4,6; Shao, Jiaan2,3; Zhao, Yanmei5; Zhang, Jiankang2,3; Zhou, Yubo4,7; Wei, Gang1; Li, Jia1,4,7
刊名BIOORGANIC CHEMISTRY
出版日期2023-09-01
卷号138页码:22
关键词Metabolic stability Four-membered heterocycles Proteasome inhibitors Multiple myeloma
ISSN号0045-2068
DOI10.1016/j.bioorg.2023.106626
通讯作者Wei, Gang(weigang@shmu.edu.cn) ; Li, Jia(jli@simm.ac.cn) ; Zhu, Huajian(zhuhj@zucc.edu.cn)
英文摘要Peptides have limitations as active pharmaceutical agents due to rapid hydrolysis by proteases and poor cell permeability. To overcome these limitations, a series of peptidyl proteasome inhibitors embedded with fourmembered heterocycles were designed to enhance their metabolic stabilities. All synthesized compounds were screened for their inhibitory activities against human 20S proteasome, and 12 target compounds displayed potent efficacy with IC50 values lower than 20 nM. Additionally, these compounds exhibited strong antiproliferative activities against multiple myeloma (MM) cell lines (MM1S: 72, IC50 = 4.86 & PLUSMN; 1.34 nM; RPMI8226: 67, IC50 = 12.32 & PLUSMN; 1.44). Metabolic stability assessments of SGF, SIF, plasma and blood were conducted, and the representative compound 73 revealed long half-lives (Plasma: T1/2 = 533 min; Blood: T1/2 > 1000 min) and good proteasome inhibitory activity in vivo. These results suggest that compound 73 serve as a lead compound for the development of more novel proteasome inhibitors.
WOS关键词DERIVATIVES ; BORTEZOMIB ; ACIDS
资助项目Scientific Research Foundation of Zhejiang University City College[X- 202202] ; Medical Health Science and Technology Project of Zhejiang-Provincial Health Commission[2023KY973] ; Medical Health Science and Technology Project of Zhejiang-Provincial Health Commission[2021KY262] ; Medical health science and technology general project of Hangzhou Health Commission[A20200357] ; Medical health science and technology major project of Hangzhou Health Commission[Z20200022] ; Medical health science and technology major project of Hangzhou Health Commission[Z20210004]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry
语种英语
WOS记录号WOS:001017006700001
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/306400]  
专题新药研究国家重点实验室
通讯作者Wei, Gang; Li, Jia; Zhu, Huajian
作者单位1.Fudan Univ, Sch Pharm, Shanghai 210023, Peoples R China
2.Hangzhou City Univ, Sch Med, Key Lab Novel Targets & Drug Study Neural Repair Z, Hangzhou 310015, Peoples R China
3.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Hangzhou Xixi Hosp, Dept pharmaceut Preparat, Hangzhou 310023, Zhejiang, Peoples R China
6.Jiangnan Univ, Sch Pharmaceut Sci, Wuxi 214122, Peoples R China
7.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Hanlin,Wu, Zhaoxiao,Cao, Yu,et al. Exploration of novel four-membered-heterocycle constructed peptidyl proteasome inhibitors with improved metabolic stability for cancer treatment[J]. BIOORGANIC CHEMISTRY,2023,138:22.
APA Wang, Hanlin.,Wu, Zhaoxiao.,Cao, Yu.,Gao, Lixin.,Shao, Jiaan.,...&Zhu, Huajian.(2023).Exploration of novel four-membered-heterocycle constructed peptidyl proteasome inhibitors with improved metabolic stability for cancer treatment.BIOORGANIC CHEMISTRY,138,22.
MLA Wang, Hanlin,et al."Exploration of novel four-membered-heterocycle constructed peptidyl proteasome inhibitors with improved metabolic stability for cancer treatment".BIOORGANIC CHEMISTRY 138(2023):22.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。