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Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays
Overexpression of coactivator associated arginine methyltransferase 1 (CARM1), a protein arginine N-methyltransferase (PRMT) family enzyme, is associated with various diseases including cancers. Consequently, the development of small-molecule inhibitors targeting PRMTs has significant value for both...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107250/ https://www.ncbi.nlm.nih.gov/pubmed/27872854 http://dx.doi.org/10.1155/2016/7086390 |
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author | Ye, Fei Zhang, Weiyao Lu, Wenchao Xie, Yiqian Jiang, Hao Jin, Jia Luo, Cheng |
author_facet | Ye, Fei Zhang, Weiyao Lu, Wenchao Xie, Yiqian Jiang, Hao Jin, Jia Luo, Cheng |
author_sort | Ye, Fei |
collection | PubMed |
description | Overexpression of coactivator associated arginine methyltransferase 1 (CARM1), a protein arginine N-methyltransferase (PRMT) family enzyme, is associated with various diseases including cancers. Consequently, the development of small-molecule inhibitors targeting PRMTs has significant value for both research and therapeutic purposes. In this study, together with structure-based virtual screening with biochemical assays, two compounds DC_C11 and DC_C66 were identified as novel inhibitors of CARM1. Cellular studies revealed that the two inhibitors are cell membrane permeable and effectively blocked proliferation of cancer cells including HELA, K562, and MCF7. We further predicted the binding mode of these inhibitors through molecular docking analysis, which indicated that the inhibitors competitively occupied the binding site of the substrate and destroyed the protein-protein interactions between CARM1 and its substrates. Overall, this study has shed light on the development of small-molecule CARM1 inhibitors with novel scaffolds. |
format | Online Article Text |
id | pubmed-5107250 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-51072502016-11-21 Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays Ye, Fei Zhang, Weiyao Lu, Wenchao Xie, Yiqian Jiang, Hao Jin, Jia Luo, Cheng Biomed Res Int Research Article Overexpression of coactivator associated arginine methyltransferase 1 (CARM1), a protein arginine N-methyltransferase (PRMT) family enzyme, is associated with various diseases including cancers. Consequently, the development of small-molecule inhibitors targeting PRMTs has significant value for both research and therapeutic purposes. In this study, together with structure-based virtual screening with biochemical assays, two compounds DC_C11 and DC_C66 were identified as novel inhibitors of CARM1. Cellular studies revealed that the two inhibitors are cell membrane permeable and effectively blocked proliferation of cancer cells including HELA, K562, and MCF7. We further predicted the binding mode of these inhibitors through molecular docking analysis, which indicated that the inhibitors competitively occupied the binding site of the substrate and destroyed the protein-protein interactions between CARM1 and its substrates. Overall, this study has shed light on the development of small-molecule CARM1 inhibitors with novel scaffolds. Hindawi Publishing Corporation 2016 2016-10-27 /pmc/articles/PMC5107250/ /pubmed/27872854 http://dx.doi.org/10.1155/2016/7086390 Text en Copyright © 2016 Fei Ye et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Ye, Fei Zhang, Weiyao Lu, Wenchao Xie, Yiqian Jiang, Hao Jin, Jia Luo, Cheng Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays |
title | Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays |
title_full | Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays |
title_fullStr | Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays |
title_full_unstemmed | Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays |
title_short | Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays |
title_sort | identification of novel inhibitors against coactivator associated arginine methyltransferase 1 based on virtual screening and biological assays |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107250/ https://www.ncbi.nlm.nih.gov/pubmed/27872854 http://dx.doi.org/10.1155/2016/7086390 |
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