Discovery of novel imidazo[2,1-b][1,3,4]thiadiazole analogs as fluorescent SHP2 inhibitors
文献类型：期刊论文
| 作者 | Zhang, Chun6; Yan, Xue3,6; Gao, Li-Xin4; Cao, Zi-Tong1,4; Cao, Qing6; Li, Jia4 ; Xiang, Da-Jun2; Zhou, Yu-Bo5; Wang, Wen-Long3,6
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| 刊名 | BIOORGANIC CHEMISTRY
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| 出版日期 | 2025-08-01 |
| 卷号 | 163页码:10 |
| 关键词 | Imidazo[2,1-b][1,3,4]thiadiazole Inhibitory activities Fluorescence imaging Zebrafish SHP2 |
| ISSN号 | 0045-2068 |
| DOI | 10.1016/j.bioorg.2025.108635 |
| 通讯作者 | Xiang, Da-Jun(xiangdjxshospital@yeah.net) ; Zhou, Yu-Bo(ybzhou@simm.ac.cn) ; Wang, Wen-Long(wenlongwang@jiangnan.edu.cn) |
| 英文摘要 | Overexpression or gene mutation of SHP2 is closely linked with a variety of cancers and has been identified as a crucial anticancer target. The fluorescent molecules have the potential for promoting novel SHP2 inhibitors development by visualizing its tissue distribution and biological behavior information. In the work, we designed and synthesized a series of imidazo[2,1-b][1,3,4]thiadiazole derivatives. Among them, several imidazo[2,1-b] [1,3,4]thiadiazole derivatives exhibited potent inhibitory activities against SHP2. The representative compound 4q demonstrated significant potency against SHP2 with IC50 of 2.89 +/- 1.60 mu M. Moreover, biological assays verified that it was efficacious in blocking the SHP2-mediated p-ERK signaling pathway and inhibited MV4-11 cell proliferation in vitro with IC50 of 7.90 +/- 0.75 mu M. In addition, compound 4q showed green fluorescence imaging in HeLa cells and zebrafish. This study provided a feasible way to develop novel fluorescent SHP2 inhibitors. |
| WOS关键词 | TYROSINE-PHOSPHATASE SHP-2 ; BIOLOGICAL EVALUATION ; DERIVATIVES ; PTPN11 ; MUTATIONS ; MECHANISM ; PROBE |
| 资助项目 | National Natural Science Foundation of China[22277043] ; Basic Research Program of Jiangsu[BK20241605] ; High Level Personnel Project of Jiangsu Prov-ince[JSSCBS20210848] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001504827700002 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318276]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xiang, Da-Jun; Zhou, Yu-Bo; Wang, Wen-Long |
| 作者单位 | 1.China Pharmaceut Univ, Inst Pharmaceut Sci, Nanjing 210009, Jiangsu, Peoples R China 2.Xishan Peoples Hosp Wuxi City, Wuxi 214105, Jiangsu, Peoples R China 3.Jiangnan Univ, Sch Chem & Mat Engn, Wuxi 214122, Jiangsu, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Stake Key Lab Chem Biol, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China 6.Jiangnan Univ, Sch Life Sci & Hlth Engn, Wuxi 214122, Jiangsu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Chun,Yan, Xue,Gao, Li-Xin,et al. Discovery of novel imidazo[2,1-b][1,3,4]thiadiazole analogs as fluorescent SHP2 inhibitors[J]. BIOORGANIC CHEMISTRY,2025,163:10. |
| APA | Zhang, Chun.,Yan, Xue.,Gao, Li-Xin.,Cao, Zi-Tong.,Cao, Qing.,...&Wang, Wen-Long.(2025).Discovery of novel imidazo[2,1-b][1,3,4]thiadiazole analogs as fluorescent SHP2 inhibitors.BIOORGANIC CHEMISTRY,163,10. |
| MLA | Zhang, Chun,et al."Discovery of novel imidazo[2,1-b][1,3,4]thiadiazole analogs as fluorescent SHP2 inhibitors".BIOORGANIC CHEMISTRY 163(2025):10. |
入库方式： OAI收割
来源：上海药物研究所
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