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Computational study on novel natural inhibitors targeting BCL2
Ideal lead compounds and candidate drugs with inhibitory effect on BCL2 were screened from ZINC database, which laid a foundation for drug development and compound improvement of drug treatment for diffuse large B-cell lymphoma (DLCBL). Identification of potential BCL2 inhibitors by computer-aided v...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280014/ https://www.ncbi.nlm.nih.gov/pubmed/34259934 http://dx.doi.org/10.1007/s12032-021-01513-x |
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author | Lv, Xiaye Jiang, Yuting Wang, Xinhui Xie, HaoQun Dou, Gaojing Wang, Jing Yang, Wenzhuo Wang, Hongyu Li, Zijian Zhang, Xiangheng Chen, Zhenghe |
author_facet | Lv, Xiaye Jiang, Yuting Wang, Xinhui Xie, HaoQun Dou, Gaojing Wang, Jing Yang, Wenzhuo Wang, Hongyu Li, Zijian Zhang, Xiangheng Chen, Zhenghe |
author_sort | Lv, Xiaye |
collection | PubMed |
description | Ideal lead compounds and candidate drugs with inhibitory effect on BCL2 were screened from ZINC database, which laid a foundation for drug development and compound improvement of drug treatment for diffuse large B-cell lymphoma (DLCBL). Identification of potential BCL2 inhibitors by computer-aided virtual screening. Libdock was applied to 17,931 compounds and the top 20 were selected for further analysis. Selected compounds were performed absorption, distribution, metabolism, and excretion (ADME) and toxicity prediction. The binding affinity between the selected ligands and BCL2 was confirmed by Molecular docking. The new natural compounds, ZINC00000255131 and ZINC00013298233, were found to bind closely with BCL2. Furthermore, they all scored lower in ames-induced mutagenicity, rodent carcinogenicity, non-developmental toxicity potential, and cytochrome P4502D6 tolerance. Molecular dynamics simulation shows that the combinations of ZINC00000255131 and ZINC00013298233 with BCL2 in the natural environment are more stable. Two new compounds, ZINC00000255131 and ZINC00013298233, were found to be potential inhibitors of BCL2. These compounds have been proved to be safe, which is of great significance for the development and improvement of DLCBL drugs. |
format | Online Article Text |
id | pubmed-8280014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-82800142021-07-20 Computational study on novel natural inhibitors targeting BCL2 Lv, Xiaye Jiang, Yuting Wang, Xinhui Xie, HaoQun Dou, Gaojing Wang, Jing Yang, Wenzhuo Wang, Hongyu Li, Zijian Zhang, Xiangheng Chen, Zhenghe Med Oncol Original Paper Ideal lead compounds and candidate drugs with inhibitory effect on BCL2 were screened from ZINC database, which laid a foundation for drug development and compound improvement of drug treatment for diffuse large B-cell lymphoma (DLCBL). Identification of potential BCL2 inhibitors by computer-aided virtual screening. Libdock was applied to 17,931 compounds and the top 20 were selected for further analysis. Selected compounds were performed absorption, distribution, metabolism, and excretion (ADME) and toxicity prediction. The binding affinity between the selected ligands and BCL2 was confirmed by Molecular docking. The new natural compounds, ZINC00000255131 and ZINC00013298233, were found to bind closely with BCL2. Furthermore, they all scored lower in ames-induced mutagenicity, rodent carcinogenicity, non-developmental toxicity potential, and cytochrome P4502D6 tolerance. Molecular dynamics simulation shows that the combinations of ZINC00000255131 and ZINC00013298233 with BCL2 in the natural environment are more stable. Two new compounds, ZINC00000255131 and ZINC00013298233, were found to be potential inhibitors of BCL2. These compounds have been proved to be safe, which is of great significance for the development and improvement of DLCBL drugs. Springer US 2021-07-14 2021 /pmc/articles/PMC8280014/ /pubmed/34259934 http://dx.doi.org/10.1007/s12032-021-01513-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Paper Lv, Xiaye Jiang, Yuting Wang, Xinhui Xie, HaoQun Dou, Gaojing Wang, Jing Yang, Wenzhuo Wang, Hongyu Li, Zijian Zhang, Xiangheng Chen, Zhenghe Computational study on novel natural inhibitors targeting BCL2 |
title | Computational study on novel natural inhibitors targeting BCL2 |
title_full | Computational study on novel natural inhibitors targeting BCL2 |
title_fullStr | Computational study on novel natural inhibitors targeting BCL2 |
title_full_unstemmed | Computational study on novel natural inhibitors targeting BCL2 |
title_short | Computational study on novel natural inhibitors targeting BCL2 |
title_sort | computational study on novel natural inhibitors targeting bcl2 |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280014/ https://www.ncbi.nlm.nih.gov/pubmed/34259934 http://dx.doi.org/10.1007/s12032-021-01513-x |
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