Development of Potent Type I Protein Arginine Methyltransferase (PRMT) Inhibitors of Leukemia Cell Proliferation

doi:10.1021/acs.jmedchem.7b01134

	Development of Potent Type I Protein Arginine Methyltransferase (PRMT) Inhibitors of Leukemia Cell Proliferation
	Wang, Chen 1,2,3; Jiang, Hao 2,3; Jin, Jia 1; Xie, Yiqian 2; Chen, Zhifeng4 ; Zhang, Hao 2; Lian, Fulin 2; Liu, Yu-Chih 5; Zhang, Chenhua 5; Ding, Hong 2; Chen, Shijie 2; Zhang, Naixia 2; Zhang, Yuanyuan 2; Jiang, Hualiang 2; Chen, Kaixian2,4 ; Ye, Fei 1; Yao, Zhiyi 6; Luo, Cheng 2
	2017-11-09
发表期刊	JOURNAL OF MEDICINAL CHEMISTRY (IF:6.8[JCR-2023],7.1[5-Year])
ISSN	0022-2623
卷号	60 期号:21 页码:8888-8905
发表状态	已发表
DOI	10.1021/acs.jmedchem.7b01134
摘要	Protein Arginine Methyltransferases (PRMTs) are crucial players in diverse biological processes, and dysregulation of PRMTs has been linked to various human diseases, especially cancer. Therefore, small molecules targeting PRMTs have profound impact for both academic functional studies and clinical disease treatment. Here, we report the discovery of N-1-(2-((2-chlorophenyl)thio)benzyl)-N-1-methylethane-1,2-diamine (28d, DCPR049_12), a highly potent inhibitor of type I PRMTs that has good selectivity against a panel of other methyltransferases. Compound 28d effectively inhibits cell proliferation in several leukemia cell lines and reduces the cellular asymmetric arginine dirnethylation levels. Serving as an effective inhibitor, 28d demonstrates the mechanism of cell killing in both cell cycle arrest and apoptotic effect as well as downregulation of the pivotal mixed lineage leukemia (MLL) fusion target genes such as HOXA9 and MEIS1, which reflects the critical roles of type I PRMTs in MLL leukemia. These studies present 28d as a valuable inhibitor to investigate the role of type I PRMTs in cancer and other diseases.
收录类别	SCI ; IC
语种	英语
资助项目	Shanghai Sailing Program[17YF1423100]
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:000415140600016
出版者	AMER CHEMICAL SOC
WOS关键词	HISTONE DEACETYLASE INHIBITOR ; GENE-EXPRESSION ; DRUG DISCOVERY ; BIOLOGICAL EVALUATION ; SELECTIVE INHIBITORS ; METHYLATION ; CANCER ; ACTIVATION ; DOCKING ; VIVO
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/10017
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_陈凯先组生命科学与技术学院_硕士生
通讯作者	Zhang, Yuanyuan; Ye, Fei; Yao, Zhiyi; Luo, Cheng
作者单位	1.Zhejiang Sci Tech Univ, Coll Life Sci, Hangzhou 310018, Zhejiang, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res,Drug Discovery & Design Ct, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China 5.Shanghai ChemPartner Co Ltd, 5 Bldg,998,Halei Rd, Shanghai 201203, Peoples R China 6.Shanghai Inst Technol, Coll Chem & Environm Engn, Shanghai 210032, Peoples R China
推荐引用方式 GB/T 7714	Wang, Chen,Jiang, Hao,Jin, Jia,et al. Development of Potent Type I Protein Arginine Methyltransferase (PRMT) Inhibitors of Leukemia Cell Proliferation[J]. JOURNAL OF MEDICINAL CHEMISTRY,2017,60(21):8888-8905.
APA	Wang, Chen.,Jiang, Hao.,Jin, Jia.,Xie, Yiqian.,Chen, Zhifeng.,...&Luo, Cheng.(2017).Development of Potent Type I Protein Arginine Methyltransferase (PRMT) Inhibitors of Leukemia Cell Proliferation.JOURNAL OF MEDICINAL CHEMISTRY,60(21),8888-8905.
MLA	Wang, Chen,et al."Development of Potent Type I Protein Arginine Methyltransferase (PRMT) Inhibitors of Leukemia Cell Proliferation".JOURNAL OF MEDICINAL CHEMISTRY 60.21(2017):8888-8905.