De Novo Design of Multitarget Ligands with an Iterative Fragment-Growing Strategy

doi:10.1021/ci500021v

CORC > 化学研究所 > 中国科学院化学研究所

	De Novo Design of Multitarget Ligands with an Iterative Fragment-Growing Strategy
	Shang, Erchang 1; Yuan, Yaxia 2; Chen, Xinyi 1; Liu, Ying 1,2; Pei, Jianfeng 2; Lai, Luhua 1,2,3
刊名	JOURNAL OF CHEMICAL INFORMATION AND MODELING
	2014-04-01
卷号	54 期号:4 页码:1235-1241
ISSN号	1549-9596
DOI	10.1021/ci500021v
英文摘要	The discovery of multitarget drugs has recently attracted much attention. Most of the reported multitarget ligands have been serendipitous discoveries. Although a few methods have been developed for rational multitarget drug discovery, there is a lack of elegant methods for de nova multitarget drug design and optimization, especially for multiple targets with large differences in their binding sites. In this paper, we report the first de nova multitarget ligand design method, with an iterative fragment-growing strategy. Using this method, dual-target inhibitors for COX-2 and LTA(4)H were designed, with the most potent one inhibiting PGE(2) and LTB4 production in the human whole blood assay with IC50 values of 7.0 and 7.1 mu M, respectively. Our strategy is generally applicable in rational and efficient multitarget drug design, especially for the design of highly integrated inhibitors for proteins with dissimilar binding pockets.
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000335201200021
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/52439]
专题	中国科学院化学研究所
通讯作者	Liu, Ying
作者单位	1.Peking Univ, Coll Chem & Mol Engn, State Key Lab Struct Chem Unstable & Stable Speci, BNLMS, Beijing 100871, Peoples R China 2.Peking Univ, AAIS, Ctr Quantitat Biol, Beijing 100871, Peoples R China 3.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
推荐引用方式 GB/T 7714	Shang, Erchang,Yuan, Yaxia,Chen, Xinyi,et al. De Novo Design of Multitarget Ligands with an Iterative Fragment-Growing Strategy[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING,2014,54(4):1235-1241.
APA	Shang, Erchang,Yuan, Yaxia,Chen, Xinyi,Liu, Ying,Pei, Jianfeng,&Lai, Luhua.(2014).De Novo Design of Multitarget Ligands with an Iterative Fragment-Growing Strategy.JOURNAL OF CHEMICAL INFORMATION AND MODELING,54(4),1235-1241.
MLA	Shang, Erchang,et al."De Novo Design of Multitarget Ligands with an Iterative Fragment-Growing Strategy".JOURNAL OF CHEMICAL INFORMATION AND MODELING 54.4(2014):1235-1241.