文献类型：期刊文献

英文题名：Perfluoro-tert-butyl Group-Derived Capmatinib: Synthesis, Biological Evaluation and Its Application in 19F Magnetic Resonance Imaging

作者：Zhang, Xinnan[1];Wang, Luting[2];Huang, Ruimin[2];Wang, Jingbo[3];Yan, Qifan[1]

机构：[1]East China Univ Sci & Technol, Prize Scientist Joint Res Ctr, Sch Chem & Mol Engn, Key Lab Adv Mat & Feringa Nobel, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China;[3]Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Sch Med, 639 Zhizaoju Rd, Shanghai 200025, Peoples R China

年份：2023

卷号：24

期号：19

外文期刊名：CHEMBIOCHEM

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001049324100001)】；

基金：The work is financially supported by the Fundamental Research Funds for the Central Universities 222201717003, National Natural Science Foundation of China 82172001, Fundamental research program funding of Ninth People's Hospital affiliated to Shanghai Jiao Tong university School of Medicine JYZZ185, and Class B project of the fifth "Nova Program" of Shanghai Institute of Materia Medica, Chinese Academy of Sciences. The authors thank Dr. Gan Luo with Shanghai Medical College of Fudan University for protein docking simulations.

语种：英文

外文关键词：F-19 MRI; Capmatinib derivatives; Targeted imaging; Fluorinated derivatization; Bioimaging

摘要：Capmatinib is an FDA-approved drug to treat metastatic non-small cell lung cancer with MET-exon 14 skipping. Herein, the perfluoro-tert-butyl group, which possesses nine chemically identical fluorine atoms, was introduced on Capmatinib to afford a targeted F-19 magnetic resonance imaging (MRI) probe, perfluoro-tert-butyl group-derived Capmatinib (9F-CAP). The F-19 MRI concentration limit was found to be 25 mM in FLASH sequence. Molecular docking simulation, surface plasmon resonance (SPR) (with a K-d of 40.7 & mu;M), half-inhibitory concentration (with a IC50 of 168 nM), Annexin V, and cytotoxicity assays jointly demonstrated that the 9F-CAP targeted cMET protein specifically. Therefore, the targeted imaging capability of 9F-CAP is of great significance for the preoperative diagnosis of specific cancers.