Virtual screening and biological evaluation of novel small molecular inhibitors against protein arginine methyltransferase 1 (PRMT1)

doi:10.1039/c4ob01591f

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Virtual screening and biological evaluation of novel small molecular inhibitors against protein arginine methyltransferase 1 (PRMT1)
	Xie, Yiqian 2,3; Zhou, Ran 3; Lian, Fulin 3; Liu, Yan 3; Chen, Limin 3; Shi, Zhe 1; Zhang, Naixia3 ; Zheng, Mingyue3 ; Shen, Bairong 2; Jiang, Hualiang3
刊名	ORGANIC & BIOMOLECULAR CHEMISTRY
	2014
卷号	12 期号:47 页码:9665-9673
ISSN号	1477-0520
DOI	10.1039/c4ob01591f
文献子类	Article
英文摘要	Protein arginine methylation is a common post-translational modification which is crucial for a variety of biological processes. Dysregulation of protein arginine methyltransferases (PRMTs) activity has been implicated in cancer and other serious diseases. Thus, small molecule inhibitors against PRMT have great potential for therapeutic development. Herein, through the combination of virtual screening and bio-assays, six small molecular compounds were identified as PRMT1 inhibitors. Amongst them, the binding affinity of compounds DCLX069 and DCLX078 with PRMT1 was further validated by T1 rho and saturation transfer difference (STD) NMR experiments. Most important of all, both compounds effectively blocked cell proliferation in breast cancer, liver cancer and acute myeloid leukemia cell lines. The binding mode analysis from molecular docking simulations theoretically indicated that both inhibitors occupied the SAM binding pocket to exert the inhibitory effect. Taken together, our compounds enriched the structural scaffolds as PRMT1 inhibitors and afforded clues for further optimization.
资助项目	Hi-Tech Research and Development Program of China[2012AA020302] ; National Natural Science Foundation of China[21210003] ; National Natural Science Foundation of China[81302700] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[21272246] ; China Postdoctoral Science Foundation[7131701713] ; Natural Science Foundation of the Jiangsu Higher Education Institutions[13KJB520022] ; Chinese Academy of Sciences (100 Talents Program)[00000000] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2014ZX09507002]
WOS关键词	ADENOSYL-L-METHIONINE ; TRANSCRIPTIONAL ACTIVATION ; IN-VIVO ; METHYLATION ; DOCKING ; BINDING ; GENE ; SPECIFICITY ; INTERACTS ; SURAMIN
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000345066100022
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277259]
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分析化学研究室战略规划处
通讯作者	Liang, Zhongjie
作者单位	1.Shanghai ChemPartner LifeSci Co Ltd, In Vitro Biol, Shanghai 201203, Peoples R China 2.Soochow Univ, Ctr Syst Biol, Suzhou 215006, Jiangsu, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Xie, Yiqian,Zhou, Ran,Lian, Fulin,et al. Virtual screening and biological evaluation of novel small molecular inhibitors against protein arginine methyltransferase 1 (PRMT1)[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2014,12(47):9665-9673.
APA	Xie, Yiqian.,Zhou, Ran.,Lian, Fulin.,Liu, Yan.,Chen, Limin.,...&Luo, Cheng.(2014).Virtual screening and biological evaluation of novel small molecular inhibitors against protein arginine methyltransferase 1 (PRMT1).ORGANIC & BIOMOLECULAR CHEMISTRY,12(47),9665-9673.
MLA	Xie, Yiqian,et al."Virtual screening and biological evaluation of novel small molecular inhibitors against protein arginine methyltransferase 1 (PRMT1)".ORGANIC & BIOMOLECULAR CHEMISTRY 12.47(2014):9665-9673.