Design, Synthesis, Biological Evaluation and Molecular Docking of Novel F-18-Labeled Focal Adhesion Kinase Inhibitors as Potential Tumor Radiotracers
Tumor diagnosis, especially at the early stages, holds immense significance. Focal adhesion kinase (FAK) is often highly expressed across various types of tumors, making it a promising target for both therapy and diagnosis. In this study, seven novel inhibitors were designed and synthesized. The inh...
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| Format: | Article |
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MDPI AG
2024-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/6/1224 |
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| author | Hailong Yang Ye Li Huaju Liang Chun Cui Lu Gan Huabei Zhang |
| author_facet | Hailong Yang Ye Li Huaju Liang Chun Cui Lu Gan Huabei Zhang |
| author_sort | Hailong Yang |
| collection | DOAJ |
| description | Tumor diagnosis, especially at the early stages, holds immense significance. Focal adhesion kinase (FAK) is often highly expressed across various types of tumors, making it a promising target for both therapy and diagnosis. In this study, seven novel inhibitors were designed and synthesized. The inhibitory activity of these compounds against FAK was notably potent, with an IC<sub>50</sub> range of 1.27–1968 nM. In particular, compounds <b>7a</b> and <b>7c</b>, with IC<sub>50</sub> values of 5.59 nM and 1.27 nM, respectively, were radiolabeled with F-18 and then evaluated with S-180 tumor-bearing mice. Subsequently, they exhibited moderate-to-high tumor uptake values, with [<sup>18</sup>F]<b>7a</b> showing 1.39 ± 0.30%ID/g at 60 min post injection and [<sup>18</sup>F]<b>7c</b> demonstrating 6.58 ± 0.46%ID/g at 30 min post injection. In addition, the results from docking studies revealed the binding specifics of the studied compounds. Overall, these findings hold the potential to offer valuable guidance for enhancing the development of radiotracers and enzyme inhibitors. |
| first_indexed | 2024-04-24T17:58:12Z |
| format | Article |
| id | doaj.art-502586b28234485dad6d1f2c1ea9be49 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-24T17:58:12Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-502586b28234485dad6d1f2c1ea9be492024-03-27T13:56:47ZengMDPI AGMolecules1420-30492024-03-01296122410.3390/molecules29061224Design, Synthesis, Biological Evaluation and Molecular Docking of Novel F-18-Labeled Focal Adhesion Kinase Inhibitors as Potential Tumor RadiotracersHailong Yang0Ye Li1Huaju Liang2Chun Cui3Lu Gan4Huabei Zhang5Key Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, No. 19 Xinjiekouwai Street, Haidian District, Beijing 100875, ChinaKey Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, No. 19 Xinjiekouwai Street, Haidian District, Beijing 100875, ChinaKey Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, No. 19 Xinjiekouwai Street, Haidian District, Beijing 100875, ChinaKey Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, No. 19 Xinjiekouwai Street, Haidian District, Beijing 100875, ChinaKey Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, No. 19 Xinjiekouwai Street, Haidian District, Beijing 100875, ChinaKey Laboratory of Radiopharmaceuticals of Ministry of Education, College of Chemistry, Beijing Normal University, No. 19 Xinjiekouwai Street, Haidian District, Beijing 100875, ChinaTumor diagnosis, especially at the early stages, holds immense significance. Focal adhesion kinase (FAK) is often highly expressed across various types of tumors, making it a promising target for both therapy and diagnosis. In this study, seven novel inhibitors were designed and synthesized. The inhibitory activity of these compounds against FAK was notably potent, with an IC<sub>50</sub> range of 1.27–1968 nM. In particular, compounds <b>7a</b> and <b>7c</b>, with IC<sub>50</sub> values of 5.59 nM and 1.27 nM, respectively, were radiolabeled with F-18 and then evaluated with S-180 tumor-bearing mice. Subsequently, they exhibited moderate-to-high tumor uptake values, with [<sup>18</sup>F]<b>7a</b> showing 1.39 ± 0.30%ID/g at 60 min post injection and [<sup>18</sup>F]<b>7c</b> demonstrating 6.58 ± 0.46%ID/g at 30 min post injection. In addition, the results from docking studies revealed the binding specifics of the studied compounds. Overall, these findings hold the potential to offer valuable guidance for enhancing the development of radiotracers and enzyme inhibitors.https://www.mdpi.com/1420-3049/29/6/1224FAKinhibitorradiotracerF-18 labelmolecular docking |
| spellingShingle | Hailong Yang Ye Li Huaju Liang Chun Cui Lu Gan Huabei Zhang Design, Synthesis, Biological Evaluation and Molecular Docking of Novel F-18-Labeled Focal Adhesion Kinase Inhibitors as Potential Tumor Radiotracers Molecules FAK inhibitor radiotracer F-18 label molecular docking |
| title | Design, Synthesis, Biological Evaluation and Molecular Docking of Novel F-18-Labeled Focal Adhesion Kinase Inhibitors as Potential Tumor Radiotracers |
| title_full | Design, Synthesis, Biological Evaluation and Molecular Docking of Novel F-18-Labeled Focal Adhesion Kinase Inhibitors as Potential Tumor Radiotracers |
| title_fullStr | Design, Synthesis, Biological Evaluation and Molecular Docking of Novel F-18-Labeled Focal Adhesion Kinase Inhibitors as Potential Tumor Radiotracers |
| title_full_unstemmed | Design, Synthesis, Biological Evaluation and Molecular Docking of Novel F-18-Labeled Focal Adhesion Kinase Inhibitors as Potential Tumor Radiotracers |
| title_short | Design, Synthesis, Biological Evaluation and Molecular Docking of Novel F-18-Labeled Focal Adhesion Kinase Inhibitors as Potential Tumor Radiotracers |
| title_sort | design synthesis biological evaluation and molecular docking of novel f 18 labeled focal adhesion kinase inhibitors as potential tumor radiotracers |
| topic | FAK inhibitor radiotracer F-18 label molecular docking |
| url | https://www.mdpi.com/1420-3049/29/6/1224 |
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