Discovery of Novel Inhibitors Targeting the Menin-Mixed Lineage Leukemia Interface Using Pharmacophore- and Docking-Based Virtual Screening

doi:10.1021/acs.jcim.6b00185

	Discovery of Novel Inhibitors Targeting the Menin-Mixed Lineage Leukemia Interface Using Pharmacophore- and Docking-Based Virtual Screening
	Xu, Yuan 1,2; Yue, Liyan 1,2; Wang, Yulan 1,2; Xing, Jin 1,2; Chen, Zhifeng4 ; Shi, Zhe 3; Liu, Rongfeng 3; Liu, Yu-Chih 3; Luo, Xiaomin 1; Jiang, Hualiang1,4 ; Chen, Kaixian1,4 ; Luo, Cheng 1; Zheng, Mingyue 1
	2016-09
发表期刊	JOURNAL OF CHEMICAL INFORMATION AND MODELING (IF:5.6[JCR-2023],5.9[5-Year])
ISSN	1549-9596
卷号	56 期号:9 页码:1847-1855
发表状态	已发表
DOI	10.1021/acs.jcim.6b00185
摘要	Disrupting the interaction between mixed lineage leukemia (MLL) fusion protein and menin provides a therapeutic approach for MLL-mediated leukemia. Here, we aim to discover novel inhibitors targeting the menin-MLL interface with virtual screening. Both structure-based molecular docking and ligand-based pharmacophore models were established, and the models used for compound screening show a remarkable ability to retrieve known active ligands from decoy molecules. Verified by a fluorescence polarization assay, five hits with novel scaffolds were identified. Among them, DCZ_M123 exhibited potent inhibitory activity with an IC50 of 4.71 +/- 0.12 mu M and a K-D of 14.70 +/- 2.13 mu M, and it can effectively inhibit the human MLL-rearranged leukemia cells MV4;11 and KOPN8 with GI(50) values of 0.84 mu M and 0.54 mu M, respectively.
收录类别	SCI ; EI
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 ; Computer Science
WOS类目	Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Computer Science, Information Systems ; Computer Science, Interdisciplinary Applications
WOS记录号	WOS:000384271400022
出版者	AMER CHEMICAL SOC
EI入藏号	20164002867279
EI主题词	Ligands ; Pharmacodynamics ; Proteins
EI分类号	Medicine and Pharmacology:461.6 ; Physical Chemistry:801.4 ; Organic Compounds:804.1
WOS关键词	MLL-FUSION PROTEINS ; TRANSFORMATION ; LEUKEMOGENESIS ; BLOCK ; GENE
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/1719
专题	生命科学与技术学院_硕士生生命科学与技术学院生命科学与技术学院_特聘教授组_陈凯先组免疫化学研究所_特聘教授组_蒋华良组
通讯作者	Luo, Cheng; Zheng, Mingyue
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Shanghai ChemPartner LifeSci Co Ltd, 5 Bldg,998 Halei Rd, Shanghai 201203, Peoples R China 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Xu, Yuan,Yue, Liyan,Wang, Yulan,et al. Discovery of Novel Inhibitors Targeting the Menin-Mixed Lineage Leukemia Interface Using Pharmacophore- and Docking-Based Virtual Screening[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING,2016,56(9):1847-1855.
APA	Xu, Yuan.,Yue, Liyan.,Wang, Yulan.,Xing, Jin.,Chen, Zhifeng.,...&Zheng, Mingyue.(2016).Discovery of Novel Inhibitors Targeting the Menin-Mixed Lineage Leukemia Interface Using Pharmacophore- and Docking-Based Virtual Screening.JOURNAL OF CHEMICAL INFORMATION AND MODELING,56(9),1847-1855.
MLA	Xu, Yuan,et al."Discovery of Novel Inhibitors Targeting the Menin-Mixed Lineage Leukemia Interface Using Pharmacophore- and Docking-Based Virtual Screening".JOURNAL OF CHEMICAL INFORMATION AND MODELING 56.9(2016):1847-1855.