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Identification of a novel c-Myc inhibitor with antitumor effects on multiple myeloma cells
Increasing evidence shows that c-Myc oncoprotein is tightly associated with multiple myeloma (MM) progression. Herein, we identified compound 7594-0035, which is a novel inhibitor that specifically targets c-Myc. It was identified from the ChemDiv compound database by molecular docking-based, high-t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146296/ https://www.ncbi.nlm.nih.gov/pubmed/30068698 http://dx.doi.org/10.1042/BSR20181027 |
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author | Yao, Ruosi Sun, Xiaoyang Xie, Yu Sun, Xiaoshen Yao, Yao Li, Hujun Li, Zhenyu Gao, Jian Xu, Kailin |
author_facet | Yao, Ruosi Sun, Xiaoyang Xie, Yu Sun, Xiaoshen Yao, Yao Li, Hujun Li, Zhenyu Gao, Jian Xu, Kailin |
author_sort | Yao, Ruosi |
collection | PubMed |
description | Increasing evidence shows that c-Myc oncoprotein is tightly associated with multiple myeloma (MM) progression. Herein, we identified compound 7594-0035, which is a novel inhibitor that specifically targets c-Myc. It was identified from the ChemDiv compound database by molecular docking-based, high-throughput virtual screening. Compound 7594-0035 inhibited MM cell proliferation in vitro, induced cell cycle G(2)-phase arrest, and triggered MM cell death by disturbing the stability of c-Myc protein. Additionally, we also found that compound 7594-0035 overcame bortezomib (BTZ) drug resistance and increased the killing effect on MM cells in combination with BTZ. The severe combined immune deficiency (SCID) mouse xenograft model revealed that compound 7594-0035 partially decreased the primary tumor growth of Roswell Park Memorial Institute (RPMI)-8226 cells in vivo. The novel small molecular compound 7594-0035 described in the present study that targets c-Myc protein is likely to be a promising therapeutic agent for relapsed/refractory MM. |
format | Online Article Text |
id | pubmed-6146296 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61462962018-09-25 Identification of a novel c-Myc inhibitor with antitumor effects on multiple myeloma cells Yao, Ruosi Sun, Xiaoyang Xie, Yu Sun, Xiaoshen Yao, Yao Li, Hujun Li, Zhenyu Gao, Jian Xu, Kailin Biosci Rep Research Articles Increasing evidence shows that c-Myc oncoprotein is tightly associated with multiple myeloma (MM) progression. Herein, we identified compound 7594-0035, which is a novel inhibitor that specifically targets c-Myc. It was identified from the ChemDiv compound database by molecular docking-based, high-throughput virtual screening. Compound 7594-0035 inhibited MM cell proliferation in vitro, induced cell cycle G(2)-phase arrest, and triggered MM cell death by disturbing the stability of c-Myc protein. Additionally, we also found that compound 7594-0035 overcame bortezomib (BTZ) drug resistance and increased the killing effect on MM cells in combination with BTZ. The severe combined immune deficiency (SCID) mouse xenograft model revealed that compound 7594-0035 partially decreased the primary tumor growth of Roswell Park Memorial Institute (RPMI)-8226 cells in vivo. The novel small molecular compound 7594-0035 described in the present study that targets c-Myc protein is likely to be a promising therapeutic agent for relapsed/refractory MM. Portland Press Ltd. 2018-09-19 /pmc/articles/PMC6146296/ /pubmed/30068698 http://dx.doi.org/10.1042/BSR20181027 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Yao, Ruosi Sun, Xiaoyang Xie, Yu Sun, Xiaoshen Yao, Yao Li, Hujun Li, Zhenyu Gao, Jian Xu, Kailin Identification of a novel c-Myc inhibitor with antitumor effects on multiple myeloma cells |
title | Identification of a novel c-Myc inhibitor with antitumor effects on multiple myeloma cells |
title_full | Identification of a novel c-Myc inhibitor with antitumor effects on multiple myeloma cells |
title_fullStr | Identification of a novel c-Myc inhibitor with antitumor effects on multiple myeloma cells |
title_full_unstemmed | Identification of a novel c-Myc inhibitor with antitumor effects on multiple myeloma cells |
title_short | Identification of a novel c-Myc inhibitor with antitumor effects on multiple myeloma cells |
title_sort | identification of a novel c-myc inhibitor with antitumor effects on multiple myeloma cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146296/ https://www.ncbi.nlm.nih.gov/pubmed/30068698 http://dx.doi.org/10.1042/BSR20181027 |
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