Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents

doi:10.1098/rsos.180176;180176

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	Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents
	Che, Jinxin 2; Wang, Zhilong 3; Sheng, Haichao 2; Huang, Feng 2; Dong, Xiaowu 2; Hu, Youhong3 ; Xie, Xin1,3 ; Hu, Yongzhou 2
刊名	ROYAL SOCIETY OPEN SCIENCE
	2018-07
卷号	5 期号:7
关键词	pharmacophore model CXCR2 antagonists anti-cancer metastasis
ISSN号	2054-5703
DOI	10.1098/rsos.180176;180176
文献子类	Article
英文摘要	Metastatic cancer is considered a fatal progression of cancer worldwide. It has been shown that a key player in this scenario is the CXC chemokine receptor 2 (CXCR2). To identify novel CXCR2 antagonists, a pharmacophore model was built with the HIPHOP program by screening a database containing compounds which were designed based on the known structure-activity relationship (SAR) of the diarylurea series CXCR2 antagonists. Compound 1a bearing the novel skeleton was selected from database screening and subjected to the in vitro biological test which showed a moderate CXCR2 antagonist potential. With further modification and exploration of SAR, compound 1e demonstrated improved CXCR2 antagonist activity with an IC50 , value of 14.8 mu M. Furthermore, wound healing assay using the NCI-H1299 cell line indicated that 1e showed an excellent anti-cancer metastatic effect (72% inhibition in cell migration at 50 mu g ml(-1).
资助项目	National Natural Science Foundation of China[81673294] ; National Natural Science Foundation of China[81472862] ; National Natural Science Foundation of China[81425024]
WOS关键词	RECEPTOR ANTAGONISTS ; PANCREATIC-CANCER ; MOLECULAR DOCKING ; TUMOR-CELLS ; DRUG DESIGN ; INHIBITORS ; POTENT ; GROWTH ; INTERLEUKIN-8 ; DERIVATIVES
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	ROYAL SOC
WOS记录号	WOS:000440143500042
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279675]
专题	国家新药筛选中心中科院受体结构与功能重点实验室新药研究国家重点实验室药物化学研究室
通讯作者	Xie, Xin; Hu, Yongzhou
作者单位	1.Chinese Acad Sci, CAS Key Lab Receptor Res, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou, Zhejiang, Peoples R China; 3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Che, Jinxin,Wang, Zhilong,Sheng, Haichao,et al. Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents[J]. ROYAL SOCIETY OPEN SCIENCE,2018,5(7).
APA	Che, Jinxin.,Wang, Zhilong.,Sheng, Haichao.,Huang, Feng.,Dong, Xiaowu.,...&Hu, Yongzhou.(2018).Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents.ROYAL SOCIETY OPEN SCIENCE,5(7).
MLA	Che, Jinxin,et al."Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents".ROYAL SOCIETY OPEN SCIENCE 5.7(2018).