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Exploration of novel 20S proteasome activators featuring anthraquinone structures and their application in hypoxic cardiomyocyte protection

文献类型：期刊论文

作者Yu, Qian5,8,9; Gao, Lixin1,4,6; Xu, Linhao7; Han, Yubing1,2,6,7; Cao, Yu7; Xi, Jianjun7; Zhong, Yigang6; Li, Linjie8,9; Shen, Liteng8,9; Che, Jinxin3,8,9
刊名BIOORGANIC & MEDICINAL CHEMISTRY
出版日期2024-12-01
卷号115页码:10
ISSN号0968-0896
DOI10.1016/j.bmc.2024.117983
通讯作者Xu, Yizhou(xuyizhou@hospital.westlake.edu.cn) ; Li, Jia(jli@simm.ac.cn) ; Zhou, Yubo(ybzhou@simm.ac.cn) ; Zhang, Jiankang(zhang_jk@hzcu.edu.cn)
英文摘要Under hypoxic conditions, the accumulation of misfolded proteins primarily relies on the autonomous activity of 20S proteasome for degradation. The buildup of toxic proteins in cardiomyocyte contribute to various cardiovascular diseases. Therefore, enhancing the 20S proteasome degradation capacity and restoring protein homeostasis in myocardial cells with small molecule activators represent a promising therapeutic strategy for the treatment of ischemic cardiomyopathy. In this study, the lead compound 8016-8398 was identified through virtual screening, and subsequent structure optimization resulted in a series of highly potent 20S proteasome activators. Intracellular protein degradation assessment revealed that these compounds possessed abilities to alleviate endoplasmic reticulum stress, as demonstrated by the luciferase reporter system. Additionally, selected compound B-03 significantly enhanced the survival rate of hypoxic-damaged cardiomyocytes. Mechanistic investigations verified B-03 rescued hypoxic damaged cardiomyocyte through apoptosis inhibition and proliferation promotion.
资助项目Zhejiang Provincial Natural Science Foundation of China[LY24H300003] ; Key R & D Program Project of Zhejiang[2022C03034] ; Con-struction Fund of Key Medical Disciplines of Hangzhou[OO20200121]
WOS研究方向Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种英语
WOS记录号WOS:001350569500001
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/314336]  
专题中国科学院上海药物研究所
通讯作者Xu, Yizhou; Li, Jia; Zhou, Yubo; Zhang, Jiankang
作者单位1.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Zhejiang Univ, Hangzhou Inst Innovat Med, Inst Drug Discovery & Design, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang Provin, Peoples R China
4.Jiangnan Univ, Sch Pharmaceut Sci, Wuxi 214122, Jiangsu Provinc, Peoples R China
5.Hangzhou City Univ, Sch Med, Key Lab Novel Targets, Drug Study Neural Repair Zhejiang Prov, Hangzhou 310015, Zhejiang, Peoples R China
6.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Guangdong Provi, Peoples R China
7.Westlake Univ, Affiliated Hangzhou Peoples Hosp 1, Sch Med, Dept Cardiol, Hangzhou 310006, Zhejiang Provin, Peoples R China
8.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang Provin, Peoples R China
9.Hangzhou Xixi Hosp, Dept Pharmaceut Preparat, Hangzhou 310023, Zhejiang Provin, Peoples R China
推荐引用方式
GB/T 7714		 Yu, Qian,Gao, Lixin,Xu, Linhao,et al. Exploration of novel 20S proteasome activators featuring anthraquinone structures and their application in hypoxic cardiomyocyte protection[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2024,115:10.
APA Yu, Qian.,Gao, Lixin.,Xu, Linhao.,Han, Yubing.,Cao, Yu.,...&Zhang, Jiankang.(2024).Exploration of novel 20S proteasome activators featuring anthraquinone structures and their application in hypoxic cardiomyocyte protection.BIOORGANIC & MEDICINAL CHEMISTRY,115,10.
MLA Yu, Qian,et al."Exploration of novel 20S proteasome activators featuring anthraquinone structures and their application in hypoxic cardiomyocyte protection".BIOORGANIC & MEDICINAL CHEMISTRY 115(2024):10.

入库方式： OAI收割

来源：上海药物研究所

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