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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...

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Autores principales: Yao, Ruosi, Sun, Xiaoyang, Xie, Yu, Sun, Xiaoshen, Yao, Yao, Li, Hujun, Li, Zhenyu, Gao, Jian, Xu, Kailin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
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.
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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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