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Computational study on novel natural compound inhibitor targeting IDH1_R132H
Isocitrate dehydrogenases (IDH) catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. IDH1 mutation has been reported in various tumors especially Cholangiocarcinoma, while the IDH1_R132H is reported to be the most common mutation of IDH1. IDH1_R132H inhibitors are effective anti-c...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320544/ https://www.ncbi.nlm.nih.gov/pubmed/35802554 http://dx.doi.org/10.18632/aging.204162 |
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author | Zhou, Baolin Yang, Fang Qin, Lei Kuai, Jun Yang, Lu Zhang, Lanfang Sun, Peisheng Li, Guangpeng Wang, Xinhui |
author_facet | Zhou, Baolin Yang, Fang Qin, Lei Kuai, Jun Yang, Lu Zhang, Lanfang Sun, Peisheng Li, Guangpeng Wang, Xinhui |
author_sort | Zhou, Baolin |
collection | PubMed |
description | Isocitrate dehydrogenases (IDH) catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. IDH1 mutation has been reported in various tumors especially Cholangiocarcinoma, while the IDH1_R132H is reported to be the most common mutation of IDH1. IDH1_R132H inhibitors are effective anti-cancer drugs and have shown significant therapeutic effects in clinical. In this study, two novel natural compounds were identified to combine respectively with IDH1_R132H with a stronger binding force with conductive to interaction energy. They also showed low toxicity potential. Molecular dynamics simulation analysis demonstrated that the candidate ligands-IDH1_R132H complexes is stable in natural circumstances with favorable potential energy. Thus, Styraxlignolide F and Tremulacin were screened as promising IDH1_R132H inhibitors. We provide a solid foundation for the design and development of IDH1_R132H targeted drugs. |
format | Online Article Text |
id | pubmed-9320544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-93205442022-07-27 Computational study on novel natural compound inhibitor targeting IDH1_R132H Zhou, Baolin Yang, Fang Qin, Lei Kuai, Jun Yang, Lu Zhang, Lanfang Sun, Peisheng Li, Guangpeng Wang, Xinhui Aging (Albany NY) Research Paper Isocitrate dehydrogenases (IDH) catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. IDH1 mutation has been reported in various tumors especially Cholangiocarcinoma, while the IDH1_R132H is reported to be the most common mutation of IDH1. IDH1_R132H inhibitors are effective anti-cancer drugs and have shown significant therapeutic effects in clinical. In this study, two novel natural compounds were identified to combine respectively with IDH1_R132H with a stronger binding force with conductive to interaction energy. They also showed low toxicity potential. Molecular dynamics simulation analysis demonstrated that the candidate ligands-IDH1_R132H complexes is stable in natural circumstances with favorable potential energy. Thus, Styraxlignolide F and Tremulacin were screened as promising IDH1_R132H inhibitors. We provide a solid foundation for the design and development of IDH1_R132H targeted drugs. Impact Journals 2022-07-07 /pmc/articles/PMC9320544/ /pubmed/35802554 http://dx.doi.org/10.18632/aging.204162 Text en Copyright: © 2022 Zhou et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zhou, Baolin Yang, Fang Qin, Lei Kuai, Jun Yang, Lu Zhang, Lanfang Sun, Peisheng Li, Guangpeng Wang, Xinhui Computational study on novel natural compound inhibitor targeting IDH1_R132H |
title | Computational study on novel natural compound inhibitor targeting IDH1_R132H |
title_full | Computational study on novel natural compound inhibitor targeting IDH1_R132H |
title_fullStr | Computational study on novel natural compound inhibitor targeting IDH1_R132H |
title_full_unstemmed | Computational study on novel natural compound inhibitor targeting IDH1_R132H |
title_short | Computational study on novel natural compound inhibitor targeting IDH1_R132H |
title_sort | computational study on novel natural compound inhibitor targeting idh1_r132h |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320544/ https://www.ncbi.nlm.nih.gov/pubmed/35802554 http://dx.doi.org/10.18632/aging.204162 |
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