Bicyclo[2.2.1]heptane containing N,N-diarylsquaramide CXCR2 selective antagonists as anti-cancer metastasis agents
文献类型：期刊论文
| 作者 | Che, Jin-Xin1; Wang, Zhi-Long3; Dong, Xiao-Wu1; Hu, You-Hong3 ; Xie, Xin2,3; Hu, Yong-Zhou1
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| 刊名 | RSC ADVANCES
 |
| 出版日期 | 2018 |
| 卷号 | 8期号:20页码:11061-11069 |
| ISSN号 | 2046-2069 |
| DOI | 10.1039/c8ra01806e |
| 文献子类 | Article |
| 英文摘要 | CXCR1 and CXCR2 are CXC chemokine receptors (CXCRs), corresponding to cytokines of the CXC chemokine family. CXCR2 was found to be 77% homologous to CXCR1. Antagonism of the chemokine receptor CXCR2 has been proposed as a new strategy for the treatment of metastatic cancer. In order to find a CXCR2 selective antagonist, a bicyclo[2.2.1]heptane containing N,N-diarylsquaramide (compound 2e) was identified by introducing a bridge ring system into the N,N-diarylsquaramide skeleton, and it exhibited good CXCR2 antagonistic activity ((IC50)-I-CXCR2 = 48 nM) and good selectivity ((IC50)-I-CXCR1/(IC50)-I-CXCR2 = 60.4). Furthermore, an in vitro biological assay of compound 2e also demonstrated its good anti-cancer metastatic effect against the pancreatic cancer cell line CFPAC1. In addition, compound 2e showed an extremely high stability in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF), as well as in rat and human plasma, but not in rat and human liver microsomes. In vivo pharmacokinetic studies in rats indicated that 2e has an excellent PK profile (10 mg kg(-1) po, C-max = 2863 ng mL(-1), t(1/2) = 2.58 h). Moreover, molecular docking was further implemented to propose the preponderant configuration of compound 2e, providing important and useful guidelines for further development. |
| WOS关键词 | HUMAN INTERLEUKIN-8 RECEPTOR ; PANCREATIC-CANCER ; GROWTH ; IMMUNOTHERAPY ; ANGIOGENESIS ; POTENT ; CELLS |
| 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 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000429534200041 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272318]  |
| 专题 | 国家新药筛选中心 药物化学研究室 |
| 通讯作者 | Xie, Xin; Hu, Yong-Zhou |
| 作者单位 | 1.Zhejiang Univ, Coll Pharmaceut Sci, ZJU ENS Joint Lab Med Chem, Hangzhou, Zhejiang, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Laborarory Drug Res, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Che, Jin-Xin,Wang, Zhi-Long,Dong, Xiao-Wu,et al. Bicyclo[2.2.1]heptane containing N,N-diarylsquaramide CXCR2 selective antagonists as anti-cancer metastasis agents[J]. RSC ADVANCES,2018,8(20):11061-11069. |
| APA | Che, Jin-Xin,Wang, Zhi-Long,Dong, Xiao-Wu,Hu, You-Hong,Xie, Xin,&Hu, Yong-Zhou.(2018).Bicyclo[2.2.1]heptane containing N,N-diarylsquaramide CXCR2 selective antagonists as anti-cancer metastasis agents.RSC ADVANCES,8(20),11061-11069. |
| MLA | Che, Jin-Xin,et al."Bicyclo[2.2.1]heptane containing N,N-diarylsquaramide CXCR2 selective antagonists as anti-cancer metastasis agents".RSC ADVANCES 8.20(2018):11061-11069. |
入库方式： OAI收割
来源：上海药物研究所
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