Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents
文献类型：期刊论文
| 作者 | Che, Jinxin2; Wang, Zhilong3; Sheng, Haichao2; Huang, Feng2; Dong, Xiaowu2; Hu, Youhong3 ; Xie, Xin1,3; Hu, Yongzhou2
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| 刊名 | ROYAL SOCIETY OPEN SCIENCE
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| 出版日期 | 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). |
| WOS关键词 | RECEPTOR ANTAGONISTS ; PANCREATIC-CANCER ; MOLECULAR DOCKING ; TUMOR-CELLS ; DRUG DESIGN ; INHIBITORS ; POTENT ; GROWTH ; INTERLEUKIN-8 ; DERIVATIVES |
| 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研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000440143500042 |
| 出版者 | ROYAL SOC |
| 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). |
入库方式： OAI收割
来源：上海药物研究所
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