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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 and limit...

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Detalles Bibliográficos
Autores principales: Zhang, Niu-niu, An, Bai-jiao, Zhou, Yan, Li, Xing-shu, Yan, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470795/
https://www.ncbi.nlm.nih.gov/pubmed/30934578
http://dx.doi.org/10.3390/molecules24061173
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author Zhang, Niu-niu
An, Bai-jiao
Zhou, Yan
Li, Xing-shu
Yan, Ming
author_facet Zhang, Niu-niu
An, Bai-jiao
Zhou, Yan
Li, Xing-shu
Yan, Ming
author_sort Zhang, Niu-niu
collection PubMed
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 31e exhibited potent antiproliferative activity (IC(50) (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 31e 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.
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spelling pubmed-64707952019-04-26 Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents Zhang, Niu-niu An, Bai-jiao Zhou, Yan Li, Xing-shu Yan, Ming Molecules Article 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 31e exhibited potent antiproliferative activity (IC(50) (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 31e 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. MDPI 2019-03-25 /pmc/articles/PMC6470795/ /pubmed/30934578 http://dx.doi.org/10.3390/molecules24061173 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Niu-niu
An, Bai-jiao
Zhou, Yan
Li, Xing-shu
Yan, Ming
Synthesis, Evaluation, and Mechanism Study of New Tepotinib Derivatives as Antiproliferative Agents
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470795/
https://www.ncbi.nlm.nih.gov/pubmed/30934578
http://dx.doi.org/10.3390/molecules24061173
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