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The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study
Farnesyltransferase has been regarded as a promising drug target against cancer as it is critical for membrane association of several signal transduction proteins. In this study, a novel farnesyltransferase inhibitor (IMB-1406) was identified through virtual screening. It exhibits stronger potency (...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421875/ https://www.ncbi.nlm.nih.gov/pubmed/28445950 http://dx.doi.org/10.18632/oncotarget.15601 |
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author | Jin, Yuanyuan Li, Linhu Yang, Zhaoyong Liu, Mingliang Guo, Huiyuan Shen, Weiyi |
author_facet | Jin, Yuanyuan Li, Linhu Yang, Zhaoyong Liu, Mingliang Guo, Huiyuan Shen, Weiyi |
author_sort | Jin, Yuanyuan |
collection | PubMed |
description | Farnesyltransferase has been regarded as a promising drug target against cancer as it is critical for membrane association of several signal transduction proteins. In this study, a novel farnesyltransferase inhibitor (IMB-1406) was identified through virtual screening. It exhibits stronger potency (IC(50)s: 6.92–8.99 μM) than Sunitinib against all of the tested cancer cell lines. Preliminary studies on mechanism reveal that IMB-1406 induces apoptosis in HepG2 cells by arresting the cell cycle at the S phase, altering anti- and pro-apoptotic proteins leading to mitochondrial dysfunction and activation of caspase-3. This anti-tumor effect is most probably related to the inhibition of farnesyltransferase as indicated by molecular docking. Overall, IMB-1406 is a novel lead compound with potent antitumor activity and deserves further structural modifications. |
format | Online Article Text |
id | pubmed-5421875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-54218752017-05-10 The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study Jin, Yuanyuan Li, Linhu Yang, Zhaoyong Liu, Mingliang Guo, Huiyuan Shen, Weiyi Oncotarget Research Paper Farnesyltransferase has been regarded as a promising drug target against cancer as it is critical for membrane association of several signal transduction proteins. In this study, a novel farnesyltransferase inhibitor (IMB-1406) was identified through virtual screening. It exhibits stronger potency (IC(50)s: 6.92–8.99 μM) than Sunitinib against all of the tested cancer cell lines. Preliminary studies on mechanism reveal that IMB-1406 induces apoptosis in HepG2 cells by arresting the cell cycle at the S phase, altering anti- and pro-apoptotic proteins leading to mitochondrial dysfunction and activation of caspase-3. This anti-tumor effect is most probably related to the inhibition of farnesyltransferase as indicated by molecular docking. Overall, IMB-1406 is a novel lead compound with potent antitumor activity and deserves further structural modifications. Impact Journals LLC 2017-02-21 /pmc/articles/PMC5421875/ /pubmed/28445950 http://dx.doi.org/10.18632/oncotarget.15601 Text en Copyright: © 2017 Jin et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Jin, Yuanyuan Li, Linhu Yang, Zhaoyong Liu, Mingliang Guo, Huiyuan Shen, Weiyi The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study |
title | The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study |
title_full | The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study |
title_fullStr | The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study |
title_full_unstemmed | The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study |
title_short | The discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study |
title_sort | discovery of a novel compound with potent antitumor activity: virtual screening, synthesis, biological evaluation and preliminary mechanism study |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421875/ https://www.ncbi.nlm.nih.gov/pubmed/28445950 http://dx.doi.org/10.18632/oncotarget.15601 |
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