Discovery of novel DNA methyltransferase 3A inhibitors via structure-based virtual screening and biological assays

doi:10.1016/j.bmcl.2016.11.023

	Discovery of novel DNA methyltransferase 3A inhibitors via structure-based virtual screening and biological assays
	Shao, Zhiyuan 1; Xu, Pan 2; Xu, Wen 3; Li, Linjuan2,4 ; Liu, Shien 2; Zhang, Rukang2,4 ; Liu, Yu-Chih 5; Zhang, Chenhua 5; Chen, Shijie 2; Luo, Cheng 2
	2017-01-15
发表期刊	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (IF:2.5[JCR-2023],2.4[5-Year])
ISSN	0960-894X
卷号	27 期号:2 页码:342-346
发表状态	已发表
DOI	10.1016/j.bmcl.2016.11.023
摘要	DNA methyltransferases are involved in diverse biological processes and abnormal methylation patterns play essential roles in cancer initiation and progression. DNA methyltransferase 3A (DNMT3A) acting as a de novo DNA methyltransferase, has gained widespread attention especially in haematological diseases. To date, large numbers of DNMTs inhibitors have been discovered, however, the small molecular inhibitors targeting DNMT3A are still in its infancy. In this study, structure-based virtual screening in combination with biological assays was performed to discovery potent novel DNMT3A inhibitors. Compound 40 and 40_3 displayed comparable in vitro inhibitory activity against DNMT3A with IC50 values of 46.5 mu M and 41 mu M, respectively. Further binding mode analysis suggested these molecules inhibit DNMT3A activity through binding the S-adenosyl-L-methionine (SAM) pocket. Overall, 40 and 40_3 may serve as novel scaffolds for further optimization and small molecular probes for investigating DNMT3A function. (C) 2016 Elsevier Ltd. All rights reserved.
关键词	Epigenetics DNMT3A inhibitors Virtual screening Molecular docking
收录类别	SCI ; IC
语种	英语
资助项目	Fund of State Key Laboratory of Toxicology and Medical Countermeasures, Academy of Military Medical Science[TMC201505]
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
WOS类目	Chemistry, Medicinal ; Chemistry, Organic
WOS记录号	WOS:000392558500043
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS关键词	METHYLATION ; DOCKING ; CANCER ; DNMT3A
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/1542
专题	生命科学与技术学院生命科学与技术学院_硕士生生命科学与技术学院_博士生
通讯作者	Chen, Shijie; Luo, Cheng
作者单位	1.Univ Sci & Technol China, Nano Sci & Technol Inst, Suzhou 215123, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 3.Fudan Univ, Obstet & Gynecol Hosp, 419 Fangxie Rd, Shanghai 200011, Peoples R China 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 5.Shanghai ChemPartner Co LTD, Pudong New Area, Bldg 5,998 Halei Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Shao, Zhiyuan,Xu, Pan,Xu, Wen,et al. Discovery of novel DNA methyltransferase 3A inhibitors via structure-based virtual screening and biological assays[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2017,27(2):342-346.
APA	Shao, Zhiyuan.,Xu, Pan.,Xu, Wen.,Li, Linjuan.,Liu, Shien.,...&Luo, Cheng.(2017).Discovery of novel DNA methyltransferase 3A inhibitors via structure-based virtual screening and biological assays.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,27(2),342-346.
MLA	Shao, Zhiyuan,et al."Discovery of novel DNA methyltransferase 3A inhibitors via structure-based virtual screening and biological assays".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 27.2(2017):342-346.