Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor
文献类型：期刊论文
| 作者 | Xie, Chengying ; Wan, Xiaozhe; Quan, Haitian; Zheng, Mingyue; Fu, Li; Li, Yun; Lou, Liguang
|
| 刊名 | CANCER SCIENCE
 |
| 出版日期 | 2018-04 |
| 卷号 | 109期号:4页码:1207-1219 |
| 关键词 | angiogenesis anlotinib tyrosine kinase inhibitor VEGF VEGFR2 |
| ISSN号 | 1349-7006 |
| DOI | 10.1111/cas.13536 |
| 文献子类 | Article |
| 英文摘要 | Abrogating tumor angiogenesis by inhibiting vascular endothelial growth factor receptor-2 (VEGFR2) has been established as a therapeutic strategy for treating cancer. However, because of their low selectivity, most small molecule inhibitors of VEGFR2 tyrosine kinase show unexpected adverse effects and limited anticancer efficacy. In the present study, we detailed the pharmacological properties of anlotinib, a highly potent and selective VEGFR2 inhibitor, in preclinical models. Anlotinib occupied the ATP-binding pocket of VEGFR2 tyrosine kinase and showed high selectivity and inhibitory potency (IC50 <1nmol/L) for VEGFR2 relative to other tyrosine kinases. Concordant with this activity, anlotinib inhibited VEGF-induced signaling and cell proliferation in HUVEC with picomolar IC50 values. However, micromolar concentrations of anlotinib were required to inhibit tumor cell proliferation directly invitro. Anlotinib significantly inhibited HUVEC migration and tube formation; it also inhibited microvessel growth from explants of rat aorta invitro and decreased vascular density in tumor tissue invivo. Compared with the well-known tyrosine kinase inhibitor sunitinib, once-daily oral dose of anlotinib showed broader and stronger invivo antitumor efficacy and, in some models, caused tumor regression in nude mice. Collectively, these results indicate that anlotinib is a well-tolerated, orally active VEGFR2 inhibitor that targets angiogenesis in tumor growth, and support ongoing clinical evaluation of anlotinib for a variety of malignancies. |
| WOS关键词 | TYROSINE KINASE INHIBITOR ; CELL LUNG-CANCER ; EPITHELIAL-MESENCHYMAL TRANSITION ; ANTIANGIOGENIC THERAPY ; ANTITUMOR-ACTIVITY ; IN-VIVO ; TUMOR MICROENVIRONMENT ; DOUBLE-BLIND ; FACTOR-C ; VEGF-D |
| 资助项目 | National Natural Science Foundation of China[81273546] ; Shanghai Science and Technology Committee[14DZ2294100] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000429411800032 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279827]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Lou, Liguang |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xie, Chengying,Wan, Xiaozhe,Quan, Haitian,et al. Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor[J]. CANCER SCIENCE,2018,109(4):1207-1219. |
| APA | Xie, Chengying.,Wan, Xiaozhe.,Quan, Haitian.,Zheng, Mingyue.,Fu, Li.,...&Lou, Liguang.(2018).Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor.CANCER SCIENCE,109(4),1207-1219. |
| MLA | Xie, Chengying,et al."Preclinical characterization of anlotinib, a highly potent and selective vascular endothelial growth factor receptor-2 inhibitor".CANCER SCIENCE 109.4(2018):1207-1219. |
入库方式： OAI收割
来源：上海药物研究所
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