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Design and Synthesis of Dual Galectin-3 and EGFR Inhibitors Against Liver Fibrosis

文献类型：期刊论文

作者Liu, Shuanglin1,4,5; He, Fei2,3; Jin, Can2,3,4; Li, Qing2,3,6; Zhao, Guilong2,3,4; Ding, Kan1,2,3,4
刊名CHEMISTRY-AN ASIAN JOURNAL
出版日期2024-11-21
页码14
关键词Galectin-3 EGFR Inhibitor Synthesis Liver fibrosis
ISSN号1861-4728
DOI10.1002/asia.202401078
通讯作者He, Fei(hefei1@simm.ac.cn) ; Zhao, Guilong(zhao_guilong@126.com) ; Ding, Kan(dingkan@simm.ac.cn)
英文摘要Liver fibrosis, mainly arising from chronic viral or metabolic liver diseases, is a significant global health concern. There is currently only one FDA-approved drug (Resmetirom) in the market to combat liver fibrosis. Both galectin-3 and epidermal growth factor receptor (EGFR) play important roles in liver fibrosis, while galectin-3 may interact with EGFR. Galectin-3 inhibitors, typically lactose or galactose derivatives may inhibit liver fibrosis. We hypothesized that targeting both galectin-3 and EGFR may have better effect against liver fibrosis. Here, EGFR inhibitor erlotinib was used in a series of designed galectin-3 inhibitors after hybridization with the pharmacophore structure in reported galectin-3 inhibitors to impede hepatic stellate cells (HSCs) activation by a typical method of click chemistry. Bioactivity test results showed that compound 29 suppressed TGF-beta-induced upregulation of fibrotic markers (alpha-SMA, fibronectin-1, and collagen I). The preferred compound 29 displayed better binding to galectin-3 (KD=52.29 mu M) and EGFR protein (KD=3.31 mu M) by SPR assay. Further docking studies were performed to clarify the possible binding mode of compound 29 with galectin-3 and EGFR. Taken together, these results suggested that compound 29 could be a potential dual galectin-3 and EGFR inhibitor as leading compound for anti-liver fibrosis new drug development.
WOS关键词PRIVILEGED STRUCTURES ; BINDING-PROTEIN ; MECHANISMS ; CELLS ; EXPRESSION ; GALNAC
资助项目National Natural Science Foundation of China[32271332] ; National Natural Science Foundation of China[31870801] ; National Natural Science Foundation of China[82341097] ; Shanghai Municipal Science and Technology Major Project, National Natural Science Foundation of China[2021B0909050003] ; High-level Innovative Research Institute ; Department of Science and Technology of Guangdong Province ; Ninth Batch of Innovative Scientific Research Team Projects from Zhongshan Science and Technology Bureau ; Zhongshan Municipal Bureau of Science and Technology ; Zhongshan Institute for Drug Discovery
WOS研究方向Chemistry
语种英语
WOS记录号WOS:001359849800001
出版者WILEY-V C H VERLAG GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/314598]  
专题中国科学院上海药物研究所
通讯作者He, Fei; Zhao, Guilong; Ding, Kan
作者单位1.Henan Univ Chinese Med, Acad Chinese Med Sci, Henan Polysaccharide Res Ctr, Henan Key Lab Chinese Med Polysaccharides & Drugs, Zhengzhou 450046, Peoples R China
2.Univ Chinese Acad Sci, 19 A Yuquan Rd, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Glycochemistry & Glycobiol Lab,State Key Lab Drug, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, SSIP Healthcare & Med Demonstrat Zone, Zhongshan 528400, Guangdong, Peoples R China
5.Henan Univ Chinese Med, Sch Pharm, Zhengzhou 450046, Henan, Peoples R China
6.Henan Univ, Sch Pharm, Kaifeng 475004, Henan, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Shuanglin,He, Fei,Jin, Can,et al. Design and Synthesis of Dual Galectin-3 and EGFR Inhibitors Against Liver Fibrosis[J]. CHEMISTRY-AN ASIAN JOURNAL,2024:14.
APA Liu, Shuanglin,He, Fei,Jin, Can,Li, Qing,Zhao, Guilong,&Ding, Kan.(2024).Design and Synthesis of Dual Galectin-3 and EGFR Inhibitors Against Liver Fibrosis.CHEMISTRY-AN ASIAN JOURNAL,14.
MLA Liu, Shuanglin,et al."Design and Synthesis of Dual Galectin-3 and EGFR Inhibitors Against Liver Fibrosis".CHEMISTRY-AN ASIAN JOURNAL (2024):14.

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来源：上海药物研究所

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