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ARV-825-induced BRD4 protein degradation as a therapy for thyroid carcinoma
Bromodomain-containing protein 4 (BRD4) is overexpressed in thyroid carcinoma, represents as an important therapeutic target. ARV-825 is a novel cereblon-based PROTAC (Proteolysis Targeting Chsimera) compound. It can induce fast and sustained BRD4 protein degradation. Its potential effect in human t...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093165/ https://www.ncbi.nlm.nih.gov/pubmed/32163373 http://dx.doi.org/10.18632/aging.102910 |
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author | He, Ling Chen, Chen Gao, Guoyu Xu, Kun Ma, Zhaoqun |
author_facet | He, Ling Chen, Chen Gao, Guoyu Xu, Kun Ma, Zhaoqun |
author_sort | He, Ling |
collection | PubMed |
description | Bromodomain-containing protein 4 (BRD4) is overexpressed in thyroid carcinoma, represents as an important therapeutic target. ARV-825 is a novel cereblon-based PROTAC (Proteolysis Targeting Chsimera) compound. It can induce fast and sustained BRD4 protein degradation. Its potential effect in human thyroid carcinoma cells was studied here. In TPC-1 cells and primary human thyroid carcinoma cells, ARV-825 potently inhibited cell viability, proliferation and migration. Furthermore, ARV-825 induced robust apoptosis activation in the thyroid carcinoma cells. ARV-825 induced BRD4 protein degradation and downregulation of its targets, including c-Myc, Bcl-xL and cyclin D1 in thyroid carcinoma cells. It was significantly more potent in inhibiting thyroid carcinoma cells than the known small molecule BRD4 inhibitors. In vivo studies demonstrated that ARV-825 oral administration potently suppressed TPC-1 xenograft tumor growth in severe combined immunodeficient mice. BRD4 protein degradation as well as c-Myc, Bcl-xL and cyclin D1 downregulation were detected in ARV-825-treated TPC-1 tumor tissues. Taken together, ARV-825 induces BRD4 protein degradation and inhibits thyroid carcinoma cell growth in vitro and in vivo. |
format | Online Article Text |
id | pubmed-7093165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-70931652020-03-30 ARV-825-induced BRD4 protein degradation as a therapy for thyroid carcinoma He, Ling Chen, Chen Gao, Guoyu Xu, Kun Ma, Zhaoqun Aging (Albany NY) Research Paper Bromodomain-containing protein 4 (BRD4) is overexpressed in thyroid carcinoma, represents as an important therapeutic target. ARV-825 is a novel cereblon-based PROTAC (Proteolysis Targeting Chsimera) compound. It can induce fast and sustained BRD4 protein degradation. Its potential effect in human thyroid carcinoma cells was studied here. In TPC-1 cells and primary human thyroid carcinoma cells, ARV-825 potently inhibited cell viability, proliferation and migration. Furthermore, ARV-825 induced robust apoptosis activation in the thyroid carcinoma cells. ARV-825 induced BRD4 protein degradation and downregulation of its targets, including c-Myc, Bcl-xL and cyclin D1 in thyroid carcinoma cells. It was significantly more potent in inhibiting thyroid carcinoma cells than the known small molecule BRD4 inhibitors. In vivo studies demonstrated that ARV-825 oral administration potently suppressed TPC-1 xenograft tumor growth in severe combined immunodeficient mice. BRD4 protein degradation as well as c-Myc, Bcl-xL and cyclin D1 downregulation were detected in ARV-825-treated TPC-1 tumor tissues. Taken together, ARV-825 induces BRD4 protein degradation and inhibits thyroid carcinoma cell growth in vitro and in vivo. Impact Journals 2020-03-12 /pmc/articles/PMC7093165/ /pubmed/32163373 http://dx.doi.org/10.18632/aging.102910 Text en Copyright © 2020 He 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 (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 He, Ling Chen, Chen Gao, Guoyu Xu, Kun Ma, Zhaoqun ARV-825-induced BRD4 protein degradation as a therapy for thyroid carcinoma |
title | ARV-825-induced BRD4 protein degradation as a therapy for thyroid carcinoma |
title_full | ARV-825-induced BRD4 protein degradation as a therapy for thyroid carcinoma |
title_fullStr | ARV-825-induced BRD4 protein degradation as a therapy for thyroid carcinoma |
title_full_unstemmed | ARV-825-induced BRD4 protein degradation as a therapy for thyroid carcinoma |
title_short | ARV-825-induced BRD4 protein degradation as a therapy for thyroid carcinoma |
title_sort | arv-825-induced brd4 protein degradation as a therapy for thyroid carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093165/ https://www.ncbi.nlm.nih.gov/pubmed/32163373 http://dx.doi.org/10.18632/aging.102910 |
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