Identifying Novel Selective Non-Nucleoside DNA Methyltransferase 1 Inhibitors through Docking-Based Virtual Screening

doi:10.1021/jm501134e

	Identifying Novel Selective Non-Nucleoside DNA Methyltransferase 1 Inhibitors through Docking-Based Virtual Screening
	Chen, Shijie 1; Wang, Yulan 1; Zhou, Wen ; Li, Shanshan 2; Peng, Jianlong 1; Shi, Zhe 3; Hu, Junchi 1; Liu, Yu-Chih 3; Ding, Hong 1; Lin, Yijyun 3; Li, Linjuan1,5 ; Cheng, Sufang 1; Liu, Jingqiu 1; Lu, Tao 2; Jiang, Hualiang1,5 ; Liu, Bo 4; Zheng, Mingyue 1; Luo, Cheng 1
	2014-11-13
发表期刊	JOURNAL OF MEDICINAL CHEMISTRY (IF:6.8[JCR-2023],7.1[5-Year])
ISSN	0022-2623
卷号	57 期号:21 页码:9028-9041
发表状态	已发表
DOI	10.1021/jm501134e
摘要	The DNA methyltransferases (DNMTs) found in mammals include DNMT1, DNMT3A, and DNMT3B and are attractive targets in cancer chemotherapy. DNMT1 was the first among the DNMTs to be characterized, and it is responsible for maintaining DNA methylation patterns. A number of DNMT inhibitors have been reported, but most of them are nucleoside analogs that can lead to toxic side effects and lack specificity. By combining docking-based virtual screening with biochemical analyses, we identified a novel compound, DC_05. DC_05 is a non-nucleoside DNMT1 inhibitor with low micromolar IC50 values and significant selectivity toward other AdoMet-dependent protein methyltransferases. Through a process of similarity-based analog searching, compounds DC_501 and DC_517 were found to be more potent than DC_05. These three potent compounds significantly inhibited cancer cell proliferation. The structure-activity relationship (SAR) and binding modes of these inhibitors were also analyzed to assist in the future development of more potent and more specific DNMT1 inhibitors.
收录类别	SCI ; IC
语种	英语
资助项目	National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2014ZX09507002-005-012]
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:000344977400025
出版者	AMER CHEMICAL SOC
WOS关键词	TUMOR-SUPPRESSOR GENES ; SMALL-MOLECULE INHIBITORS ; CANCER-CELL LINES ; METHYLATION INHIBITORS ; EPIGENETIC THERAPY ; PROTEIN ; INSIGHTS ; COMPLEX ; REACTIVATION ; HYDRALAZINE
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/2363
专题	生命科学与技术学院免疫化学研究所_特聘教授组_蒋华良组生命科学与技术学院_博士生
通讯作者	Liu, Bo
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.China Pharmaceut Univ, Sch Sci, Lab Mol Design & Drug Discovery, Nanjing 210009, Peoples R China 3.Shanghai ChemPartner Co Ltd, Shanghai 201203, Peoples R China 4.Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangdong Prov Acad Chinese Med Sci, Guangzhou 510006, Guangdong, Peoples R China 5.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Chen, Shijie,Wang, Yulan,Zhou, Wen,et al. Identifying Novel Selective Non-Nucleoside DNA Methyltransferase 1 Inhibitors through Docking-Based Virtual Screening[J]. JOURNAL OF MEDICINAL CHEMISTRY,2014,57(21):9028-9041.
APA	Chen, Shijie.,Wang, Yulan.,Zhou, Wen.,Li, Shanshan.,Peng, Jianlong.,...&Luo, Cheng.(2014).Identifying Novel Selective Non-Nucleoside DNA Methyltransferase 1 Inhibitors through Docking-Based Virtual Screening.JOURNAL OF MEDICINAL CHEMISTRY,57(21),9028-9041.
MLA	Chen, Shijie,et al."Identifying Novel Selective Non-Nucleoside DNA Methyltransferase 1 Inhibitors through Docking-Based Virtual Screening".JOURNAL OF MEDICINAL CHEMISTRY 57.21(2014):9028-9041.