Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents
Inspired by the potent inhibition activity of the c-Met (mesenchymal−epithelial transition factor) inhibitor Tepotinib, a series of new Tepotinib derivatives were synthesized and evaluated for their ability to act as antiproliferative agents to find the leading compounds with good activity...
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MDPI AG
2019-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/6/1173 |
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| author | Niu-niu Zhang Bai-jiao An Yan Zhou Xing-shu Li Ming Yan |
| author_facet | Niu-niu Zhang Bai-jiao An Yan Zhou Xing-shu Li Ming Yan |
| author_sort | Niu-niu Zhang |
| collection | DOAJ |
| description | Inspired by the potent inhibition activity of the c-Met (mesenchymal−epithelial transition factor) inhibitor Tepotinib, a series of new Tepotinib derivatives were synthesized and evaluated for their ability to act as antiproliferative agents to find the leading compounds with good activity and limited side effects. Among them, compound <b>31e</b> exhibited potent antiproliferative activity (IC<sub>50</sub> (50% inhibitory concentration) = 0.026 μΜ) against hepatic carcinoma 97H (human liver cancer cell) cells and, importantly, had very low inhibitory activity against normal cells. A mechanism study demonstrated that <b>31e</b> induced G1 phase (First growth phase or G indicating gap) arrest, inhibited the phosphorylation of c-Met and its downstream signaling component, Akt (Protein Kinase B), and also inhibited the migration of hepatic carcinoma 97H cells. |
| first_indexed | 2024-04-13T16:12:18Z |
| format | Article |
| id | doaj.art-eaeb4444979a47d39777c08e14c4343c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T16:12:18Z |
| publishDate | 2019-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-eaeb4444979a47d39777c08e14c4343c2022-12-22T02:40:13ZengMDPI AGMolecules1420-30492019-03-01246117310.3390/molecules24061173molecules24061173Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative AgentsNiu-niu Zhang0Bai-jiao An1Yan Zhou2Xing-shu Li3Ming Yan4Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaInstitute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaInstitute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaInstitute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaInstitute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaInspired by the potent inhibition activity of the c-Met (mesenchymal−epithelial transition factor) inhibitor Tepotinib, a series of new Tepotinib derivatives were synthesized and evaluated for their ability to act as antiproliferative agents to find the leading compounds with good activity and limited side effects. Among them, compound <b>31e</b> exhibited potent antiproliferative activity (IC<sub>50</sub> (50% inhibitory concentration) = 0.026 μΜ) against hepatic carcinoma 97H (human liver cancer cell) cells and, importantly, had very low inhibitory activity against normal cells. A mechanism study demonstrated that <b>31e</b> induced G1 phase (First growth phase or G indicating gap) arrest, inhibited the phosphorylation of c-Met and its downstream signaling component, Akt (Protein Kinase B), and also inhibited the migration of hepatic carcinoma 97H cells.https://www.mdpi.com/1420-3049/24/6/1173antiproliferative agentsc-Met inhibitor97H cellslow toxicity |
| spellingShingle | Niu-niu Zhang Bai-jiao An Yan Zhou Xing-shu Li Ming Yan Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents Molecules antiproliferative agents c-Met inhibitor 97H cells low toxicity |
| title | Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents |
| title_full | Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents |
| title_fullStr | Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents |
| title_full_unstemmed | Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents |
| title_short | Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents |
| title_sort | synthesis evaluation and mechanism study of new tepotinib derivatives as antiproliferative agents |
| topic | antiproliferative agents c-Met inhibitor 97H cells low toxicity |
| url | https://www.mdpi.com/1420-3049/24/6/1173 |
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