Discovery of Multitarget Inhibitors by Combining Molecular Docking with   Common Pharmacophore Matching

doi:10.1021/jm8010096

CORC > 北京大学 > 化学与分子工程学院

	Discovery of Multitarget Inhibitors by Combining Molecular Docking with Common Pharmacophore Matching
	Wei, Dengguo ; Jiang, Xiaolu ; Zhou, Lu ; Chen, Jing ; Chen, Zheng ; He, Chong ; Yang, Kun ; Liu, Ying ; Pei, Jianfeng ; Lai, Luhua
刊名	journal of medicinal chemistry
	2008
关键词	LEUKOTRIENE A(4) HYDROLASE DESIGNED MULTIPLE LIGANDS TIGHT-BINDING INHIBITORS NMDA RECEPTOR ANTAGONIST DRUG DISCOVERY POTENT INHIBITORS LTA(4) HYDROLASE LOW-AFFINITY NETWORK ANALOGS
DOI	10.1021/jm8010096
英文摘要	Multitarget drugs have been to be found effective in controlling complex diseases. However, how to design multitarget drugs presents a great challenge. We have developed a computer-assisted strategy to screen for multitarget inhibitors using a combination of molecular docking and common pharmacophore matching. This strategy was successfully applied to screen for dual-target inhibitors against both the human leukotriene A(4) hydrolase (LTA4H-h) and the human nonpancreatic secretory phospholipase A2 (hnps-PLA2). Three compounds screened from the chemical database MDL Available Chemical Directory were found to inhibit these two enzymes at the 10 mu M level. Moreover, one synthetic compound matching the common pharmacophores inhibits LTA4H-h and hnps-PLA2 with IC(50) values of 35 nM and 7.3 mu M, respectively. The common pharmacophore model can also be used to search small molecule databases or collections of existing inhibitors, as well as to guide combinatorial library design to search for ideal multitarget inhibitors.; Chemistry, Medicinal; SCI(E); PubMed; 69; ARTICLE; 24; 7882-7888; 51
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/150144]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Wei, Dengguo,Jiang, Xiaolu,Zhou, Lu,et al. Discovery of Multitarget Inhibitors by Combining Molecular Docking with Common Pharmacophore Matching[J]. journal of medicinal chemistry,2008.
APA	Wei, Dengguo.,Jiang, Xiaolu.,Zhou, Lu.,Chen, Jing.,Chen, Zheng.,...&Lai, Luhua.(2008).Discovery of Multitarget Inhibitors by Combining Molecular Docking with Common Pharmacophore Matching.journal of medicinal chemistry.
MLA	Wei, Dengguo,et al."Discovery of Multitarget Inhibitors by Combining Molecular Docking with Common Pharmacophore Matching".journal of medicinal chemistry (2008).