Pharmacophore-Based Virtual Screening and Biological Evaluation of Small Molecule Inhibitors for Protein Arginine Methylation
文献类型：期刊论文
| 作者 | Wang, Juxian3; Chen, Limin2; Sinha, Sarmistha Halder3; Liang, Zhongjie2; Chai, Huifang1; Muniyan, Sakthivel5; Chou, Yu-Wei5; Yang, Chao3; Yan, Leilei3; Feng, You3 |
| 刊名 | JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2012-09-27 |
| 卷号 | 55期号:18页码:7978-7987 |
| ISSN号 | 0022-2623 |
| DOI | 10.1021/jm300521m |
| 文献子类 | Article |
| 英文摘要 | Protein arginine methyltransferases (PRMTs) are proved to play vital roles in chromatin remodeling, RNA metabolism, and signal transduction. Aberrant regulation of PRMT activity is associated with various pathological states such as cancer and cardiovascular disorders. Development and application of small molecule PRMT inhibitors will provide new avenues for therapeutic discovery. The combination of pharmacophore-based virtual screening methods with radioactive methylation assays provided six hits identified as inhibitors against the predominant arginine methyltransferase PRMT1 within micromolar potency. Two potent compounds, A9 and A36, exhibited the inhibitory effect by directly targeting substrate H4 other than PRMT1 and displayed even higher inhibition activity than the well-known PRMT inhibitors AMI-1. A9 significantly inhibits proliferation of castrate-resistant prostate cancer cells. Together, A9 may be a potential inhibitor against advanced hormone-independent cancers, and the work will provide clues for the future development of specific compounds that block the interaction of PRMTs with their targets. |
| WOS关键词 | METHYLTRANSFERASES ; ACETYLTRANSFERASE ; DISCOVERY ; DOCKING ; EMBRYO |
| 资助项目 | National Institutes of Health (NIH)[CA88184] ; American Heart Association[00000000] ; Georgia Cancer Coalition Distinguished Cancer Scholar Award[00000000] ; State Key Program of Basic Research of China[2009CB918502] ; National Natural Science Foundation of China[20972174] ; National Natural Science Foundation of China[91029704] ; National Natural Science Foundation of China[81270622] ; National Natural Science Foundation of China[21210003] ; National High Technology Research and Development Program of China[2012AA020302] ; Chinese Academy of Sciences[XDA01040305] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000309153500004 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277940]  |
| 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 | Luo, Cheng |
| 作者单位 | 1.Guiyang Coll Tradit Chinese Med, Dept Pharm, Guiyang 550002, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Materia Medica, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 3.Georgia State Univ, Program Mol Basis Dis, Dept Chem, Atlanta, GA 30302 USA; 4.Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, State Key Lab Med Genom,Shanghai Inst Hematol, Shanghai 200030, Peoples R China; 5.Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA |
| 推荐引用方式 GB/T 7714 | Wang, Juxian,Chen, Limin,Sinha, Sarmistha Halder,et al. Pharmacophore-Based Virtual Screening and Biological Evaluation of Small Molecule Inhibitors for Protein Arginine Methylation[J]. JOURNAL OF MEDICINAL CHEMISTRY,2012,55(18):7978-7987. |
| APA | Wang, Juxian.,Chen, Limin.,Sinha, Sarmistha Halder.,Liang, Zhongjie.,Chai, Huifang.,...&Luo, Cheng.(2012).Pharmacophore-Based Virtual Screening and Biological Evaluation of Small Molecule Inhibitors for Protein Arginine Methylation.JOURNAL OF MEDICINAL CHEMISTRY,55(18),7978-7987. |
| MLA | Wang, Juxian,et al."Pharmacophore-Based Virtual Screening and Biological Evaluation of Small Molecule Inhibitors for Protein Arginine Methylation".JOURNAL OF MEDICINAL CHEMISTRY 55.18(2012):7978-7987. |
入库方式： OAI收割
来源：上海药物研究所
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