Dynamic Modeling of Human 5-Lipoxygenase-Inhibitor Interactions Helps To   Discover Novel Inhibitors

doi:10.1021/jm201497k

CORC > 北京大学 > 化学与分子工程学院

	Dynamic Modeling of Human 5-Lipoxygenase-Inhibitor Interactions Helps To Discover Novel Inhibitors
	Wu, Yiran ; He, Chong ; Gao, Yang ; He, Shan ; Liu, Ying ; Lai, Luhua
刊名	journal of medicinal chemistry
	2012
关键词	PROSTAGLANDIN E-2 SYNTHASE-1 HUMAN WHOLE-BLOOD 3-DIMENSIONAL STRUCTURES THERAPEUTIC TARGET POTENT INHIBITORS DUAL INHIBITORS CYCLOOXYGENASE BIOSYNTHESIS INFLAMMATION LICOFELONE
DOI	10.1021/jm201497k
英文摘要	Human 5-lipoxygenase (5-LOX) is one of the key anti-inflammatory drug targets due to its key role in leukotrienes biosynthesis. We have built a model for the active conformation of human 5-LOX using comparative modeling, docking of known inhibitors, and molecular dynamics simulation. Using this model, novel 5-LOX inhibitors were identified by virtual screen. Of the 105 compounds tested in a cell-free assay, 30 have IC50 values less than 100 mu M and 11 less than 10 mu M with the strongest inhibition of 620 nM. Compounds 4, 7, and 11 showed strong inhibition activity in the human whole blood (HWB) assay with IC50 values of 8.6, 9.7, 8.1 mu M, respectively. Moreover, compounds 4 and 7 were also found to inhibit microsomal prostaglandin E synthase (mPGES)-1 with micromolar IC50 values, similar to licofelone, a dual functional inhibitor of 5-LOX/mPGES-1. The compounds reported here provide new scaffolds for anti-inflammatory drug design.; Chemistry, Medicinal; SCI(E); PubMed; 0; ARTICLE; 6; 2597-2605; 55
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/312579]
专题	化学与分子工程学院生命科学学院
推荐引用方式 GB/T 7714	Wu, Yiran,He, Chong,Gao, Yang,et al. Dynamic Modeling of Human 5-Lipoxygenase-Inhibitor Interactions Helps To Discover Novel Inhibitors[J]. journal of medicinal chemistry,2012.
APA	Wu, Yiran,He, Chong,Gao, Yang,He, Shan,Liu, Ying,&Lai, Luhua.(2012).Dynamic Modeling of Human 5-Lipoxygenase-Inhibitor Interactions Helps To Discover Novel Inhibitors.journal of medicinal chemistry.
MLA	Wu, Yiran,et al."Dynamic Modeling of Human 5-Lipoxygenase-Inhibitor Interactions Helps To Discover Novel Inhibitors".journal of medicinal chemistry (2012).