Identification of PRMT5 inhibitors with novel scaffold structures through virtual screening and biological evaluations
文献类型：期刊论文
| 作者 | Zhang, Qian1; Zhang, Lun1; Jin, Jia1; Fan, Yaohua2; Wang, Xiaoguang2; Hu, Haofeng1; Ye, Xiaoqing1,3; Wang, Lei1; Cao, Chenxi2; Ye, Fei1 |
| 刊名 | JOURNAL OF MOLECULAR MODELING
 |
| 出版日期 | 2022-07 |
| 卷号 | 28期号:7页码:184 |
| 关键词 | PRMT5 Small-molecule inhibitors Virtual screening Molecular docking Molecular dynamics simulations |
| ISSN号 | 1610-2940 |
| DOI | 10.1007/s00894-022-05125-8 |
| 文献子类 | Article |
| 英文摘要 | Protein arginine methyltransferase 5 (PRMT5), an important member in PRMT family, has been validated as a promising anticancer target. In this study, through the combination of virtual screening and biological experiments, we have identified two PRMT5 inhibitors with novel scaffold structures. Among them, compound Y2431 showed moderate activity with IC50 value of 10.09 mu M and displayed good selectivity against other methyltransferases. The molecular docking analysis and molecular dynamics (MD) simulations suggested that the compound occupied the substrate-arginine binding site. Furthermore, Y2431 exhibited anti-proliferative activity to leukemia cells by inducing cell cycle arrest. Overall, the hit compound could provide a novel scaffold for further optimization of small-molecule PRMT5 inhibitors. |
| WOS关键词 | ARGININE METHYLTRANSFERASE 5 ; DISCOVERY ; METHYLATION ; DOCKING ; GENERATION ; SOFTWARE ; POTENT ; MODEL |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Chemistry ; Computer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000809881100001 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309332]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Cao, Chenxi; Ye, Fei |
| 作者单位 | 1.Zhejiang Sci Tech Univ, Coll Life Sci & Med, Hangzhou, Peoples R China; 2.Jia Xing Univ, Dept Surg, Affiliated Hosp 2, Jiaxing, Peoples R China; 3.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Materta Med, State Key Lab Drug Res, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Qian,Zhang, Lun,Jin, Jia,et al. Identification of PRMT5 inhibitors with novel scaffold structures through virtual screening and biological evaluations[J]. JOURNAL OF MOLECULAR MODELING,2022,28(7):184. |
| APA | Zhang, Qian.,Zhang, Lun.,Jin, Jia.,Fan, Yaohua.,Wang, Xiaoguang.,...&Ye, Fei.(2022).Identification of PRMT5 inhibitors with novel scaffold structures through virtual screening and biological evaluations.JOURNAL OF MOLECULAR MODELING,28(7),184. |
| MLA | Zhang, Qian,et al."Identification of PRMT5 inhibitors with novel scaffold structures through virtual screening and biological evaluations".JOURNAL OF MOLECULAR MODELING 28.7(2022):184. |
入库方式： OAI收割
来源：上海药物研究所
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