2. Academic Validation
  3. Discovery of novel imidazo[2,1-b][1,3,4]thiadiazole analogs as fluorescent SHP2 inhibitors

Discovery of novel imidazo[2,1-b][1,3,4]thiadiazole analogs as fluorescent SHP2 inhibitors

  • Bioorg Chem. 2025 May 27:163:108635. doi: 10.1016/j.bioorg.2025.108635.
Chun Zhang 1,  Xue Yan 2,  Li-Xin Gao 3,  Zi-Tong Cao 4,  Qing Cao 1,  Jia Li 3,  Da-Jun Xiang 5,  Yu-Bo Zhou 6,  Wen-Long Wang 7
Affiliations

Affiliations

  • 1 School of Life Sciences and Health Engineering, Jiangnan University, Jiangsu 214122, China.
  • 2 School of Life Sciences and Health Engineering, Jiangnan University, Jiangsu 214122, China; School of Chemical and Material Engineering, Jiangnan University, Jiangsu, 214122, China.
  • 3 Stake Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 4 Stake Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
  • 5 Xishan People's Hospital of Wuxi City, Wuxi, Jiangsu 214105, China. Electronic address: xiangdjxshospital@yeah.net.
  • 6 Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, SSIP Healthcare and Medicine Demonstration Zone, Zhongshan Tsuihang New District, Zhongshan 528400, China. Electronic address: ybzhou@simm.ac.cn.
  • 7 School of Life Sciences and Health Engineering, Jiangnan University, Jiangsu 214122, China; School of Chemical and Material Engineering, Jiangnan University, Jiangsu, 214122, China. Electronic address: wenlongwang@jiangnan.edu.cn.
PMID: 40466301 DOI: 10.1016/j.bioorg.2025.108635
Abstract

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 μM. 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 μM. 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.

Keywords

Fluorescence imaging; Imidazo[2,1-b][1,3,4]thiadiazole; Inhibitory activities; SHP2; Zebrafish.

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