Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays
文献类型：期刊论文
| 作者 | Ye, Fei1,2; Zhang, Weiyao1; Lu, Wenchao3,4; Xie, Yiqian3; Jiang, Hao3,4; Jin, Jia1; Luo, Cheng3
|
| 刊名 | BIOMED RESEARCH INTERNATIONAL
 |
| 出版日期 | 2016 |
| ISSN号 | 2314-6133 |
| DOI | 10.1155/2016/7086390 |
| 文献子类 | Article |
| 英文摘要 | 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. |
| WOS关键词 | TRANSCRIPTIONAL COACTIVATOR ; PYRAZOLE INHIBITORS ; GENE-EXPRESSION ; DRUG DISCOVERY ; HISTONE H3 ; CARM1 ; METHYLATION ; DOCKING ; CANCER ; INSIGHTS |
| 资助项目 | Zhejiang Province Natural Science Foundation[LQ14H300003] ; National Natural Science Foundation of China[81402849] ; Public Projects of Zhejiang Province[2015C33159] ; Public Projects of Zhejiang Province[2016C31017] ; Zhejiang Provincial Top Key Discipline of Biology, Science Foundation of Zhejiang Sci-Tech University (ZSTU)[13042163-Y] ; Zhejiang Provincial Top Key Discipline of Biology, Science Foundation of Zhejiang Sci-Tech University (ZSTU)[13042159-Y] ; 521 Talent Cultivation Plan of Zhejiang Sci-Tech University[00000000] |
| WOS研究方向 | Biotechnology & Applied Microbiology ; Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:000387395300001 |
| 出版者 | HINDAWI PUBLISHING CORP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276192]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Ye, Fei; Jin, Jia |
| 作者单位 | 1.Zhejiang Sci Tech Univ, Coll Life Sci, Hangzhou, Zhejiang, Peoples R China; 2.Key Lab Plant Secondary Metab & Regulat Zhejiang, Hangzhou, Zhejiang, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai, Peoples R China; 4.Univ Chinese Acad Sci, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ye, Fei,Zhang, Weiyao,Lu, Wenchao,et al. Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays[J]. BIOMED RESEARCH INTERNATIONAL,2016. |
| APA | Ye, Fei.,Zhang, Weiyao.,Lu, Wenchao.,Xie, Yiqian.,Jiang, Hao.,...&Luo, Cheng.(2016).Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays.BIOMED RESEARCH INTERNATIONAL. |
| MLA | Ye, Fei,et al."Identification of Novel Inhibitors against Coactivator Associated Arginine Methyltransferase 1 Based on Virtual Screening and Biological Assays".BIOMED RESEARCH INTERNATIONAL (2016). |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。